Sample records for g199a ncol del

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Minicollagen-15, a novel minicollagen isolated from Hydra, forms tubule structures in nematocysts.

    PubMed

    Adamczyk, Patrizia; Meier, Sebastian; Gross, Thomas; Hobmayer, Bert; Grzesiek, Stephan; Bächinger, Hans Peter; Holstein, Thomas W; Ozbek, Suat

    2008-02-29

    Minicollagens constitute a family of unusually short collagen molecules isolated from cnidarians. They are restricted to the nematocyst, a cylindrical explosive organelle serving in defense and capture of prey. The nematocyst capsule contains a long tubule inside of its matrix, which is expelled and everted during an ultrafast discharge process. Here, we report the cloning and characterization of a novel minicollagen in Hydra, designated minicollagen-15 (NCol-15). NCol-15, like NCol-3 and NCol-4, shows deviations from the canonical cysteine pattern in its terminal cysteine-rich domains (CRDs). Minicollagens share common domain architectures with a central collagen sequence flanked by polyproline stretches and short N- and C-terminal CRDs. The CRDs are involved in the formation of a highly resistant cysteine network, which constitutes the basic structure of the nematocyst capsule. Unlike NCol-1, which is part of the capsule wall, NCol-15 is localized to tubules, arguing for a functional differentiation of minicollagens within the nematocyst architecture. NMR analysis of the altered C-terminal CRD of NCol-15 showed a novel disulfide-linked structure within the cysteine-containing region exhibiting similar folding kinetics and stability as the canonical CRDs. Our data provide evidence for evolutionary diversification among minicollagens, which probably facilitated alterations in the morphology of the nematocyst wall and tubule.

  8. Design of a colicin E7 based chimeric zinc-finger nuclease

    NASA Astrophysics Data System (ADS)

    Németh, Eszter; Schilli, Gabriella K.; Nagy, Gábor; Hasenhindl, Christoph; Gyurcsik, Béla; Oostenbrink, Chris

    2014-08-01

    Colicin E7 is a natural bacterial toxin. Its nuclease domain (NColE7) enters the target cell and kills it by digesting the nucleic acids. The HNH-motif as the catalytic centre of NColE7 at the C-terminus requires the positively charged N-terminal loop for the nuclease activity—offering opportunities for allosteric control in a NColE7-based artificial nuclease. Accordingly, four novel zinc finger nucleases were designed by computational methods exploiting the special structural features of NColE7. The constructed models were subjected to MD simulations. The comparison of structural stability and functional aspects showed that these models may function as safely controlled artificial nucleases. This study was complemented by random mutagenesis experiments identifying potentially important residues for NColE7 function outside the catalytic region.

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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.

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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] ...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 63. G.F.H., photographer July 30, 1932 DEL NORTE COUNTY, SECTION ...

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

    63. G.F.H., photographer July 30, 1932 DEL NORTE COUNTY, SECTION A, HIGHWAY 1. 1-DN A #124, STA. 164=00 SHOWING DRAINAGE CONDITIONS, G.F.H., 7-30-32. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. Evaluation of HLA-G 14-bp ins/del and +3142G>C polymorphisms with susceptibility to recurrent spontaneous abortion.

    PubMed

    Hashemi, Mohammad; Mokhtari, Mojgan; Khazaeian, Safura; Bahari, Gholamreza; Rezaei, Maryam; Nakhaee, Alireza; Taheri, Mohsen

    2017-06-01

    HLA-G is critically important for successful implantation during pregnancy. Increasing evidence supposed that HLA-G plays a key role in tolerance of the semi-allogeneic graft in pregnancy by inhibiting the cytotoxic functions of T and NK cells. The present study aimed to evaluate the impact of HLA-G rs1063320 (+3142G>C) and 14-bp insertion (ins)/deletion (del) polymorphisms on recurrent spontaneous abortion (RSA). Genomic DNA from 93 RSA patients and 93 normal fertile women was isolated using the salting out method. Genotyping of HLA-G +3142G>C and 14-bp ins/del variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. The HLA-G +3142G>C polymorphism increased the risk of RSA in codominant (OR = 2.39, 95%CI = 1.27-4.49, p = 0.010, GC vs GG; OR = 3.28, 95%CI = 1.16-9.72, p = 0.040, CC vs GG) and dominant (OR = 2.52, 95%CI = 1.37-4.64, p = 0.004, GC + CC vs GG) tested inheritance models. HLA-G rs1063320 C allele was associated with increased risk of RSA (OR = 1.84, 95%CI = 1.20-2.83, p = 0.007). The del/del genotype as well as del allele of 14-bp ins/del variant increased that risk of RSA (OR = 3.02, 95%CI = 1.23-7.41, p = 0.025 and OR = 1.65, 95%CI = 1.09-2.50, p = 0.022, respectively). In summary, our results showed that HLA-G gene polymorphisms significantly increased the risk of RSA in a sample of the Iranian population. Copyright © 2017. Published by Elsevier B.V.

  19. 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...

  20. The effect of the common c.2299delG mutation in USH2A on RNA splicing.

    PubMed

    Lenassi, Eva; Saihan, Zubin; Bitner-Glindzicz, Maria; Webster, Andrew R

    2014-05-01

    Recessive variants in the USH2A gene are an important cause of both Usher syndrome and nonsyndromic retinitis pigmentosa. A single base-pair deletion in exon 13 (c.2299delG, p.Glu767Serfs*21) is considered the most frequent mutation of USH2A. It is predicted to generate a premature termination codon and is presumed to lead to nonsense mediated decay. However the effect of this variant on RNA has not been formally investigated. It is not uncommon for exonic sequence alterations to cause aberrant splicing and the aim of the present report is to evaluate the effect of c.2299delG on USH2A transcripts. Nasal cells represent the simplest available tissue to study splicing defects in USH2A. Nasal brushing, RNA extraction from nasal epithelial cells and reverse transcription PCR were performed in five Usher syndrome patients who were homozygous for c.2299delG, two unaffected c.2299delG heterozygotes and seven control individuals. Primers to amplify between exons 12 and 15 and exons 10 and 14 were utilised. Significant variability was observed between different RT-PCR experiments. Importantly, in controls, PCR product of the expected size were amplified on all occasions (13/13 experiments); for patients this was true in only 4/14 experiments (Fisher exact test p = 0.0002). Bioinformatics tools predict the c.2299delG change to disrupt an exonic splicing enhancer and to create an exonic splicing silencer within exon 13. Here, we report an effect of the common c.2299delG mutation on splicing of exons 12 and 13 of USH2A. Future studies are expected to provide important insights into the contribution of this effect on the phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  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. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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] ...

  7. 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] ...

  8. 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] ...

  9. 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] ...

  10. 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] ...

  11. 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] ...

  12. 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] ...

  13. 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] ...

  14. 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] ...

  15. 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] ...

  16. 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] ...

  17. 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] ...

  18. 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] ...

  19. 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] ...

  20. 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] ...

  1. 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...

  2. 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] ...

  3. 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] ...

  4. 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] ...

  5. 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] ...

  6. 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] ...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.

    PubMed

    Donaldson, Scott H; Pilewski, Joseph M; Griese, Matthias; Cooke, Jon; Viswanathan, Lakshmi; Tullis, Elizabeth; Davies, Jane C; Lekstrom-Himes, Julie A; Wang, Linda T

    2018-01-15

    Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. To evaluate the safety and efficacy of tezacaftor monotherapy and of tezacaftor/ivacaftor combination therapy in subjects with cystic fibrosis homozygous for F508del or compound heterozygous for F508del and G551D. This was a randomized, placebo-controlled, double-blind, multicenter, phase 2 study (NCT01531673). Subjects homozygous for F508del received tezacaftor (10 to 150 mg) every day alone or in combination with ivacaftor (150 mg every 12 h) in a dose escalation phase, as well as in a dosage regimen testing phase. Subjects compound heterozygous for F508del and G551D, taking physician-prescribed ivacaftor, received tezacaftor (100 mg every day). Primary endpoints were safety through Day 56 and change in sweat chloride from baseline through Day 28. Secondary endpoints included change in percent predicted FEV 1 (ppFEV 1 ) from baseline through Day 28 and pharmacokinetics. The incidence of adverse events was similar across treatment arms. Tezacaftor (100 mg every day)/ivacaftor (150 mg every 12 h) resulted in a 6.04 mmol/L decrease in sweat chloride and 3.75 percentage point increase in ppFEV 1 in subjects homozygous for F508del, and a 7.02 mmol/L decrease in sweat chloride and 4.60 percentage point increase in ppFEV 1 in subjects compound heterozygous for F508del and G551D from baseline through Day 28 (P < 0.05 for all). These results support continued clinical development of tezacaftor (100 mg every day) in combination with ivacaftor (150 mg every 12 h) in subjects with cystic fibrosis. Clinical trial registered with www.clinicaltrials.gov (NCT01531673).

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. The USH2A c.2299delG mutation: dating its common origin in a Southern European population

    PubMed Central

    Aller, Elena; Larrieu, Lise; Jaijo, Teresa; Baux, David; Espinós, Carmen; González-Candelas, Fernando; Nájera, Carmen; Palau, Francesc; Claustres, Mireille; Roux, Anne-Françoise; Millán, José M

    2010-01-01

    Usher syndrome type II is the most common form of Usher syndrome. USH2A is the main responsible gene of the three known to be disease causing. It encodes two isoforms of the protein usherin. This protein is part of an interactome that has an essential role in the development and function of inner ear hair cells and photoreceptors. The gene contains 72 exons spanning over a region of 800 kb. Although numerous mutations have been described, the c.2299delG mutation is the most prevalent in several populations. Its ancestral origin was previously suggested after the identification of a common core haplotype restricted to 250 kb in the 5′ region that encodes the short usherin isoform. By extending the haplotype analysis over the 800 kb region of the USH2A gene with a total of 14 intragenic single nucleotide polymorphisms, we have been able to define 10 different c.2299delG haplotypes, showing high variability but preserving the previously described core haplotype. An exhaustive c.2299delG/control haplotype study suggests that the major source of variability in the USH2A gene is recombination. Furthermore, we have evidenced twice the amount of recombination hotspots located in the 500 kb region that covers the 3′ end of the gene, explaining the higher variability observed in this region when compared with the 250 kb of the 5′ region. Our data confirm the common ancestral origin of the c.2299delG mutation. PMID:20145675

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  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. 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...

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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.

  1. Calculation of (P,T) -odd electric dipole moments for the diamagnetic atoms X129e , Y171b , H199g , R211n , and R225a

    NASA Astrophysics Data System (ADS)

    Dzuba, V. A.; Flambaum, V. V.; Porsev, S. G.

    2009-09-01

    Electric dipole moments of diamagnetic atoms of experimental interest are calculated using the relativistic Hartree-Fock and random-phase approximation methods, the many-body perturbation theory, and the configuration-interaction technique. We consider (P,T) -odd interactions, which give rise to atomic electric dipole moment in the second order of the perturbation theory. These include nuclear Schiff moment, (P,T) -odd electron-nucleon interaction, and electron electric dipole moment. Interpretation of an experimental constraint of a permanent electric dipole moment of H199g [W. C. Griffith, M. D. Swallows, T. H. Loftus, M. V. Romalis, B. R. Heckel, and E. N. Fortson, Phys. Rev. Lett. 102, 101601 (2009)] is discussed.

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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.

  7. 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

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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. ...

  1. 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...

  2. 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...

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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

  9. 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.

  10. 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.

  11. Prevalence of 2314delG mutation in Spanish patients with Usher syndrome type II (USH2).

    PubMed

    Beneyto, M M; Cuevas, J M; Millán, J M; Espinós, C; Mateu, E; González-Cabo, P; Baiget, M; Doménech, M; Bernal, S; Ayuso, C; García-Sandoval, B; Trujillo, M J; Borrego, S; Antiñolo, G; Carballo, M; Nájera, C

    2000-06-01

    The Usher syndrome (USH) is a group of autosomal recessive diseases characterized by congenital sensorineural hearing loss and retinitis pigmentosa. Three clinically distinct forms of Usher syndrome have so far been recognized and can be distinguished from one another by assessing auditory and vestibular function. Usher syndrome type II (USH2) patients have congenital moderate-to-severe nonprogressive hearing loss, retinitis pigmentosa, and normal vestibular function. Genetic linkage studies have revealed genetic heterogeneity among the three types of USH, with the majority of USH2 families showing linkage to the USH2A locus in 1q41. The USH2A gene (MIM 276901) has been identified: three mutations, 2314delG, 2913delG, and 4353-54delC, were initially reported in USH2A patients, the most frequent of which is the 2314delG mutation. It has been reported that this mutation can give rise to typical and atypical USH2 phenotypes. USH2 cases represent 62% of all USH cases in the Spanish population, and 95% of these cases have provided evidence of linkage to the USH2A locus. In the present study, the three reported mutations were analyzed in 59 Spanish families with a diagnosis of USH type II. The 2314delG was the only mutation identified in our population: it was detected in 25% of families and 16% of USH2 chromosomes analyzed. This study attempts to estimate the prevalence of this common mutation in a homogeneous Spanish population.

  12. 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

  13. [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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. [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.

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. Benzo[g]indoles

    NASA Astrophysics Data System (ADS)

    Pozharskii, A. F.; Kachalkina, S. G.; Gulevskaya, A. V.; Filatova, E. A.

    2017-07-01

    The data on the synthesis and properties of benzo[g]indoles accumulated mainly over a period of the past 15-20 years are integrated. Various variants of pyrrole ring and naphthalene nucleus closure are considered. It is demonstrated that, in addition to the expected similarity between benzo[g]indoles and indoles, there are noticeable differences between them as well, especially where the synthesis of the benzoindole system is concerned. Practical applications of benzo[g]indoles are discussed. The bibliography includes 199 references.

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. 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...

  17. 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.

  18. 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...

  19. 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

  20. 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.

  1. 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

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. Efficacy Outcome Measures for Clinical Trials of USH2A caused by the Common c.2299delG Mutation.

    PubMed

    Calzetti, Giacomo; Levy, Richard A; Cideciyan, Artur V; Garafalo, Alexandra V; Roman, Alejandro J; Sumaroka, Alexander; Charng, Jason; Heon, Elise; Jacobson, Samuel G

    2018-06-25

    To determine the change in vision and retinal structure in patients with the common c.2299delG mutation in the USH2A gene in anticipation of clinical trials of therapy. Retrospective observational case series. Eighteen patients, homozygotes or compound heterozygotes with the c.2299delG mutation in USH2A, were studied with visual acuity, kinetic perimetry, dark- and light-adapted two-color static perimetry, optical coherence tomography (OCT) and autofluorescence (AF) imaging. Serial data were available for at least half of the patients depending on the parameter analyzed. The kinetics of disease progression in this specific molecular form of USH2A differed between the measured parameters. Visual acuity could remain normal for decades. Kinetic and light-adapted static perimetry across the entire visual field had similar rates of decline that were slower than those of rod-based perimetry. Horizontal OCT scans through the macula showed that IS/OS line width had a similar rate of constriction as co-localized AF imaging and cone-based light-adapted sensitivity extent. The rate of constriction of rod-based sensitivity extent across this same region was twice as rapid as that of cones. In patients with the c.2299delG mutation in USH2A, rod photoreceptors are the cells that express disease early and more aggressively than cones. Rod-based vision measurements in central or extracentral-peripheral retinal regions warrant monitoring in order to complete a clinical trial in a timely manner. Copyright © 2018. Published by Elsevier Inc.

  9. 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.

  10. 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

  11. 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.

  12. 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...

  13. 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...

  14. 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...

  15. Methylation of 6-mercaptopurine and 6-thioguanine by thiopurine S-methyltransferase. A comparison of activity in red blood cell samples of 199 blood donors.

    PubMed

    Kröplin, T; Iven, H

    2000-07-01

    To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equal molar concentrations of 6-TG and 6-MP as substrates. After extraction, the reaction products 6-methyl-TG and 6-methyl-MP were quantified using specific high-performance liquid chromatography procedures. The medians of the TPMT activities from 199 blood donors were 54.4 nmol 6-MTG g(-1)Hb h(-1) when measured with 6-TG as the substrate and 35.8 nmol 6-MMP g(-1) Hb h(-1) when measured with 6-MP. The correlation coefficient for the 199 pairs of values was 0.8695. On average, TPMT activity was 34% lower with 6-MP as substrate than with 6-TG as substrate.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. CHEK2 1100delC, IVS2+1G>A and I157T mutations are not present in colorectal cancer cases from Turkish population.

    PubMed

    Bayram, Süleyman; Topaktaş, Mehmet; Akkız, Hikmet; Bekar, Aynur; Akgöllü, Ersin

    2012-10-01

    The cell cycle checkpoint kinase 2 (CHEK2) protein participates in the DNA damage response in many cell types. Germline mutations in CHEK2 (1100delC, IVS2+1G>A and I157T) have been impaired serine/threonine kinase activity and associated with a range of cancer types. This hospital-based case-control study aimed to investigate whether CHEK2 1100delC, IVS2+1G>A and I157T mutations play an important role in the development of colorectal cancer (CRC) in Turkish population. A total of 210 CRC cases and 446 cancer-free controls were genotyped for CHEK2 mutations by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-polymerase chain reaction (AS-PCR) methods. We did not find the CHEK2 1100delC, IVS2+1G>A and I157T mutations in any of the Turkish subjects. Our result demonstrate for the first time that CHEK2 1100delC, IVS2+1G>A and I157T mutations have not been agenetic susceptibility factor for CRC in the Turkish population. Overall, our data suggest that genotyping of CHEK2 mutations in clinical settings in the Turkish population should not be recommended. However, independent studies are need to validate our findings in a larger series, as well as in patients of different ethnic origins. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. Production and characterization of multi-polysaccharide degrading enzymes from Aspergillus aculeatus BCC199 for saccharification of agricultural residues.

    PubMed

    Suwannarangsee, Surisa; Arnthong, Jantima; Eurwilaichitr, Lily; Champreda, Verawat

    2014-10-01

    Enzymatic hydrolysis of lignocellulosic biomass into fermentable sugars is a key step in the conversion of agricultural by-products to biofuels and value-added chemicals. Utilization of a robust microorganism for on-site production of biomass-degrading enzymes has gained increasing interest as an economical approach for supplying enzymes to biorefinery processes. In this study, production of multi-polysaccharide-degrading enzymes from Aspergillus aculeatus BCC199 by solid-state fermentation was improved through the statistical design approach. Among the operational parameters, yeast extract and soybean meal as well as the nonionic surfactant Tween 20 and initial pH were found as key parameters for maximizing production of cellulolytic and hemicellulolytic enzymes. Under the optimized condition, the production of FPase, endoglucanase, β-glucosidase, xylanase, and β-xylosidase was achieved at 23, 663, 88, 1,633, and 90 units/g of dry substrate, respectively. The multi-enzyme extract was highly efficient in the saccharification of alkaline-pretreated rice straw, corn cob, and corn stover. In comparison with commercial cellulase preparations, the BCC199 enzyme mixture was able to produce remarkable yields of glucose and xylose, as it contained higher relative activities of β-glucosidase and core hemicellulases (xylanase and β-xylosidase). These results suggested that the crude enzyme extract from A. aculeatus BCC199 possesses balanced cellulolytic and xylanolytic activities required for the efficient saccharification of lignocellulosic biomass feedstocks, and supplementation of external β-glucosidase or xylanase was dispensable. The work thus demonstrates the high potential of A. aculeatus BCC199 as a promising producer of lignocellulose-degrading enzymes for the biomass conversion industry.

  6. 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

  7. 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.

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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

  14. 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.

  15. 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...

  16. 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...

  17. 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.

  18. The novel c.247_249delTTC (p.F83del) GJB2 mutation in a family with prelingual sensorineural deafness.

    PubMed

    Petersen, Michael B; Grigoriadou, Maria; Koutroumpe, Maria; Kokotas, Haris

    2012-07-01

    Non-syndromic hearing loss is one of the most common hereditary determined diseases in human, and the disease is a genetically heterogeneous disorder. Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of non-syndromic recessive hearing impairment in many countries and are largely dependent on ethnic groups. Due to the high frequency of the c.35delG GJB2 mutation in the Greek population, we have previously suggested that Greek patients with sensorineural, non-syndromic deafness should be tested for the c.35delG mutation and the coding region of the GJB2 gene should be sequenced in c.35delG heterozygotes. Here we present on the clinical and molecular genetic evaluation of a family suffering from prelingual, sensorineural, non-syndromic deafness. A novel c.247_249delTTC (p.F83del) GJB2 mutation was detected in compound heterozygosity with the c.35delG GJB2 mutation in the proband and was later confirmed in the father, while the mother was homozygous for the c.35delG GJB2 mutation. We conclude that compound heterozygosity of the novel c.247_249delTTC (p.F83del) and the c.35delG mutations in the GJB2 gene was the cause of deafness in the proband and his father. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. Fabry disease: Evidence for a regional founder effect of the GLA gene mutation 30delG in Brazilian patients.

    PubMed

    de Alencar, Dayse Oliveira; Netto, Cristina; Ashton-Prolla, Patricia; Giugliani, Roberto; Ribeiro-Dos-Santos, Ândrea; Pereira, Fernanda; Matte, Ursula; Santos, Ney; Santos, Sidney

    2014-01-01

    The Fabry disease is caused by mutations in the gene ( GLA ) that encodes the enzyme α-galactosidase A (α-Gal A). More than 500 pathologic variants of GLA have already been described, most of them are family-specific. In southern Brazil, a frequent single-base deletion ( GLA 30delG) was identified among four families that do not recognize any common ancestral. In order to investigate the history of this mutation (investigate the founder effect, estimate the mutation age and the most likely source), six gene-flanking microsatellite markers of the X chromosome on the mutation carriers and their parents, 150 individuals from the same population and 300 individuals that compose the Brazilian parental populations (Europeans, Africans and Native Americans) were genotyped. A common haplotype to the four families was identified and characterized as founder. The age was estimated with two statistics software (DMLE 2.2 and ESTIAGE) that agreed with 11 to 12 generations old. This result indicates that the mutation GLA 30delG was originated from a single event on the X chromosome of a European immigrant, during the southern Brazil colonization between 1710 and 1740.

  4. Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family

    PubMed Central

    Wang, Xiran; Pei, Yu; Dou, Jingtao; Lu, Juming; Li, Jian; Lv, Zhaohui

    2015-01-01

    Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients’ diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI. PMID:25983617

  5. 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.

  6. 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.

  7. 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...

  8. 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

  9. [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.

  10. 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

  11. 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

  12. The 14 bp Del/Ins HLA-G polymorphism is related with high blood pressure in acute coronary syndrome and type 2 diabetes mellitus.

    PubMed

    García-González, Ilian Janet; Valle, Yeminia; Rivas, Fernando; Figuera-Villanueva, Luis Eduardo; Muñoz-Valle, José Francisco; Flores-Salinas, Hector Enrique; Gutiérrez-Amavizca, Bianca Ethel; Dávalos-Rodríguez, Nory Omayra; Padilla-Gutiérrez, Jorge Ramón

    2014-01-01

    Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (OR(c) = 1.65, P = 0.02). The genetic recessive model showed similar findings (OR(c) = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups.

  13. The 14 bp Del/Ins HLA-G Polymorphism Is Related with High Blood Pressure in Acute Coronary Syndrome and Type 2 Diabetes Mellitus

    PubMed Central

    García-González, Ilian Janet; Valle, Yeminia; Rivas, Fernando; Figuera-Villanueva, Luis Eduardo; Muñoz-Valle, José Francisco; Flores-Salinas, Hector Enrique; Gutiérrez-Amavizca, Bianca Ethel; Dávalos-Rodríguez, Nory Omayra; Padilla-Gutiérrez, Jorge Ramón

    2014-01-01

    Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (ORc = 1.65, P = 0.02). The genetic recessive model showed similar findings (ORc = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups. PMID:24689061

  14. 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

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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

  7. 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.

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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 mi

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. 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

  13. 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

  14. Novel Compound Heterozygous CLCNKB Gene Mutations (c.1755A>G/ c.848_850delTCT) Cause Classic Bartter Syndrome.

    PubMed

    Wang, Chunli; Chen, Ying; Zheng, Bixia; Zhu, Mengshu; Fan, Jia; Wang, Juejin; Jia, Zhanjun; Huang, Songming; Zhang, Aihua

    2018-02-14

    Inactivated variants in CLCNKB gene encoding the basolateral chloride channel ClC-Kb cause classic Bartter syndrome characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here we identified two cBS siblings presenting hypokalemia in a Chinese family due to novel compound heterozygous CLCNKB mutations (c.848_850delTCT/c.1755A>G). Compound heterozygosity was confirmed by amplifying and sequencing the patient's genomic DNA. The synonymous mutation c.1755A>G (Thr585Thr) was located at +2bp from the 5' splice donor site in exon 15, further transcript analysis demonstrated that this single nucleotide mutation causes exclusion of exon 15 in the cDNA from the proband and his mother. Furthermore, we investigated the expression and protein trafficking change of c.848_850delTCT (TCT) and exon 15 deletion（E15）mutation in vitro. The E15 mutation markedly decreased the expression of ClC-Kb and resulted in a low-molecular-weight band (~55kD) trapping in the endoplasmic reticulum, while the TCT mutant only decreased the total and plasma membrane ClC-Kb protein expression but did not affect the subcellular localization. Finally, we studied the physiological functions of mutations by using whole-cell patch clamp and found that E15 or TCT mutation decreased the current of ClC-Kb/barttin channel. These results suggested that the compound defective mutations of CLCNKB gene are the molecular mechanism of the two cBS siblings.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma.

    PubMed

    Coco, Simona; De Mariano, Marilena; Valdora, Francesca; Servidei, Tiziana; Ridola, Vita; Andolfo, Immacolata; Oberthuer, André; Tonini, Gian Paolo; Longo, Luca

    2012-10-01

    The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous system, a tissue in which ALK is expressed during embryonic development. We performed an ALK mutation screening in 52 MBs and we found a novel heterozygous germline deletion of a single base in exon 23 (3605delG) in a case with marked anaplasia. This G deletion results in a frameshift mutation producing a premature stop codon in exon 25 of ALK tyrosine kinase domain. We also screened three human MB cell lines without finding any mutation of ALK gene. Quantitative expression analysis of 16 out of 52 samples showed overexpression of ALK mRNA in three MBs. In the present study, we report the first mutation of ALK found in MB. Moreover, a deletion of ALK gene producing a stop codon has not been detected in human tumors up to now. Further investigations are now required to elucidate whether the truncated form of ALK may have a role in signal transduction.

  1. Evaluation of Lumipulse® G1200 for the measurement of six tumor markers: Comparison with AIA® 2000.

    PubMed

    de Rancher, Marie-Aude Robert; Oudart, Jean-Baptiste; Maquart, François-Xavier; Monboisse, Jean Claude; Ramont, Laurent

    2016-11-01

    Tumor marker assays are daily practiced, for screening and follow up of cancers. Interassay precision is an important parameter for the interpretation of the kinetics of the markers, in order to conclude to the efficiency or failure of treatment. The aim of this study was to compare two automated Immunoassay analyzers, Lumipulse® G1200 and AIA® 2000. Both analyzers used an immunoassay system but with different antibodies. Six tumor markers commonly used were studied: AFP, PSA, CA 19-9, CA 15-3, CA 125 and CEA. 253 samples have been collected over a period of one month and analyzed by both analyzers. Regression of Passing-Badblock and Bland-Altman diagram were used to analyze the results for AFP (n=36), PSA (n=39), CA-125 (n=40), CA 15-3 (n=40), CA 19-9 (n=46) and CEA (n=52) were performed. Analytical performances of Lumipulse® G1200 highlighted the good inter-run and intra-run precision of the analyzer. We obtained a good correlation coefficient between Lumipulse G1200® and AIA 2000®, >0.96 for most markers except CA 19-9 which provided a correlation coefficient significantly lower than that obtained with other markers. The concordance for all markers was >94% except for CA 19-9 (83.7%). This study showed a good correlation between the two analyzers and, therefore, a transfer from one analyzer to the other is possible for the different markers studied. However, we found here the classical difficulty to transfer this type of analysis, due to the absence of method standardization. This difficulty was particularly illustrated by CA19-9. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  2. 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...

  3. 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.

  4. The HLA-G Genetic Contribution to Bipolar Disorder: A Trans-Ethnic Replication.

    PubMed

    Sundaresh, Aparna; Wu, Ching-Lien; Chinnadurai, Raj Kumar; Rajkumar, Ravi Philip; Mariaselvam, Christina Mary; LeMaoult, Joël; Krishnamoorthy, Rajagopal; Leboyer, Marion; Negi, Vir Singh; Tamouza, Ryad

    2018-05-08

    Bipolar disorder (BD) is frequently associated with immune dysfunctions. Studying the genetic diversity of the immuno-modulatory human leukocyte antigen (HLA)-G locus in a French BD cohort, we previously reported an association between a functionally relevant 14 bp Ins/Del polymorphism and BD risk. The present study investigated the genetic and expression diversities of HLA-G in a geographically distinct South Indian population-group BD patients, as well as the influence of exposure to the neurotropic Toxoplasma gondii pathogen. Three functionally relevant HLA-G polymorphisms, i.e. HLA-G 14 bp Ins/Del (rs66554220), +3142G>C (rs1063320) and +3187A>G (rs9380142) were genotyped by polymerase chain reaction (PCR) and real-time PCR. Sub-samples of BD patients and healthy controls (HC) were investigated for plasma levels of soluble HLA-G (sHLA-G) isoforms, as well as circulating stigma of T. gondii infection. Findings indicate: (i) the frequency of the HLA-G 14 bp Del/Del genotype was higher in BD cases, as compared to HC; (ii) the HLA-G + 3142 C allele and CC genotype were more prevalent in BD patients than in HC; (iii) sHLA-G levels were significantly higher in BD cases, especially in females and in the early onset sub-group; and (iv) the InsGA haplotype was more prevalent in HC. Our findings further support the genetic contribution of HLA-G to BD risk, as well as indicate relevant expression profiles. Such data may also indicate a potential developmental role in BD etiology, given that HLA-G is an important immune regulator from the intrauterine period and across development.

  5. 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.

  6. Poussée de maladie de Kaposi et élévation du CA 19-9: penser à la tuberculose!

    PubMed Central

    Ajili, Faida; Hariz, Héla; Souissi, Asmahen; Abid, Rim; Boussetta, Najeh; Laabidi, Besma; Battikh, Riadh; Louzir, Bassem; Othmani, Salah

    2013-01-01

    La maladie de Kaposi (MK) est une entité pathologique qui peut survenir chez les patients VIH positifs et dans le cadre d'une immunodépression, d'origine tuberculeuse très rarement. On décrit le cas d'une MK chez un patient VIH négatif au décours d'une tuberculose. Nous rapportons le cas d'un patient âgé de 81 ans, VIH négatif, ayant présenté deux nodules angiomateux de l'avant bras gauche dont la biopsie cutanée était en faveur d'une MK. L’évolution était marquée 2 mois plus tard, par l'apparition de placards angiomateux extensifs des deux membres supérieurs et d'adénopathies cervicales jugulo-carotidiennes bilatérales. La biopsie ganglionnaire était en faveur d'une tuberculose ganglionnaire. Par ailleurs, il avait un taux sérique élevé des CA 19-9. La régression de l’étendue des lésions au niveau des membres supérieurs et la normalisation du taux sérique des CA 19-9 ont été obtenues sous traitement anti-tuberculeux. Chez les patients atteints d'une MK avec une élévation des CA 19-9, il faut penser à la tuberculose. PMID:24711871

  7. 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

  8. 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.

  9. 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

  10. Recent Origin and Spread of a Common Lithuanian Mutation, G197del LDLR, Causing Familial Hypercholesterolemia: Positive Selection Is Not Always Necessary to Account for Disease Incidence among Ashkenazi Jews

    PubMed Central

    Durst, Ronen; Colombo, Roberto; Shpitzen, Shoshi; Avi, Liat Ben; Friedlander, Yechiel; Wexler, Roni; Raal, Frederick J.; Marais, David A.; Defesche, Joep C.; Mandelshtam, Michail Y.; Kotze, Maritha J.; Leitersdorf, Eran; Meiner, Vardiella

    2001-01-01

    G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on disease expression. Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The Netherlands (n=1), and the United States (n=1) were enlisted. All trace their ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208-D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the deletion was found to be 20 ± 7 generations (the 95% confidence interval is 15–26 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 14th century. This corresponds with the founding of the Jewish community of Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ individuals in eastern Europe, which followed this settlement. The penetrance of mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no significant differences in the mean baseline lipid level of G197del carriers from different countries were found. Polymorphisms of apolipoprotein E and of scavenger-receptor class B type I were observed to have minor effects on the plasma lipid profile. With respect to determinative genetic influences on the biochemical phenotype, there is no evidence that could support the possibility of a selective evolutionary metabolic advantage. Therefore, the founder effect in a rapidly expanding population from a limited number of families remains a simple, parsimonious

  11. 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.

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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…

  17. 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...

  18. 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

  19. 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.

  20. [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.

  1. 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...

  2. 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.

  3. Deferasirox associated with liver failure and death in a sickle cell anemia patient homozygous for the -1774delG polymorphism in the Abcc2 gene.

    PubMed

    Braga, Caroline C B; Benites, Bruno Deltreggia; de Albuquerque, Dulcineia M; Alvarez, Marisa C; Seva-Pereira, Tiago; Duarte, Bruno K L; Costa, Fernando F; Gilli, Simone C O; Saad, Sara T O

    2017-08-01

    This manuscript describes the case of a patient with sickle cell anemia who died of fulminant hepatitis after therapy with the iron chelator Deferasirox. The patient was homozygous for the -1774delG polymorphism in the Abcc2 gene, which raises the concern about the use of hepatotoxic drugs in this specific context.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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

  10. 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.

  11. 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

  12. [Antigens (CEA and CA 19-9) in diagnosis and prognosis colorectal cancer].

    PubMed

    Grotowski, Maciej

    2002-01-01

    carcinoembryonic antigen (CEA) was first described more than three decades ago, when its presence was demonstrated in fetal gut tissue and in tumors from gastrointestinal tract. Subsequently, CEA was detected in the circulation of patients and recognized as a serum marker for colorectal cancer. This tumor marker has not been advocated as a screening test for colorectal cancer, however a preoperative CEA serum level is useful for diagnosis and prognosis of recurrence and survival in colorectal cancer patients. The levels of CEA increased with increasing tumor stage. Expression of carbohydrate antigen (CA 19-9) has been described in various malignancies and also in colorectal cancer. This antigen also has not been advocated as a screening test for colorectal cancer. The levels of CA 19-9 increased in advanced stages of colorectal cancer. Despite its lower sensitivity than CEA in early stages of colorectal cancer, the combination of both antigens can provided more information than CEA alone for prognosis of recurrence and survival in those patients.

  13. 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.

  14. 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.

  15. 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.

  16. Detection of early pancreatic ductal adenocarcinoma using thrombospondin-2 and CA19-9 blood markers

    PubMed Central

    Kim, Jungsun; Bamlet, William R.; Oberg, Ann L.; Chaffee, Kari G.; Donahue, Greg; Cao, Xing-Jun; Chari, Suresh; Garcia, Benjamin A.; Petersen, Gloria M.; Zaret, Kenneth S.

    2017-01-01

    Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model that recapitulated the progression of human PDAC, we identified secreted proteins and tested and validated a subset of them as potential markers of PDAC. We optimized an ELISA assay using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls. Clinical studies including a phase 1 discovery study (N=20 patients), a phase 2a validation study (N=189), and a second phase 2b validation study (N=537) revealed that concentrations of plasma thrombospondin-2 (THBS2) discriminated among all stages of PDAC consistently over the three studies with a Receiver Operating Characteristic (ROC) c-statistic of 0.76 in Phase 1, 0.842 in Phase 2a, and 0.875 in Phase 2b. The concentration of THBS2 in plasma performed as well at discriminating resectable stage I cancer as stage III/IV PDAC. THBS2 concentrations combined with those for CA19-9, a previously identified PDAC marker, yielded a c-statistic of 0.956 in the Phase 2a study and 0.970 in the Phase 2b study. THBS2 data improved the ability of CA19-9 to distinguish PDAC from pancreatitis. With a specificity of 98%, the combination of THBS2 and CA19-9 yielded a sensitivity of 87% for PDAC in the Phase 2b study. Given this, a THBS2 and CA19-9 panel assessed in human blood using a conventional ELISA assay may improve the detection of patients at high risk for PDAC. PMID:28701476

  17. Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers.

    PubMed

    Kim, Jungsun; Bamlet, William R; Oberg, Ann L; Chaffee, Kari G; Donahue, Greg; Cao, Xing-Jun; Chari, Suresh; Garcia, Benjamin A; Petersen, Gloria M; Zaret, Kenneth S

    2017-07-12

    Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model that recapitulated the progression of human PDAC, we identified secreted proteins and tested a subset as potential markers of PDAC. We optimized an enzyme-linked immunosorbent assay (ELISA) using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls. A phase 1 discovery study ( n = 20), a phase 2a validation study ( n = 189), and a second phase 2b validation study ( n = 537) revealed that concentrations of plasma thrombospondin-2 (THBS2) discriminated among all stages of PDAC consistently. The receiver operating characteristic (ROC) c-statistic was 0.76 in the phase 1 study, 0.84 in the phase 2a study, and 0.87 in the phase 2b study. The plasma concentration of THBS2 was able to discriminate resectable stage I cancer as readily as stage III/IV PDAC tumors. THBS2 plasma concentrations combined with those for CA19-9, a previously identified PDAC marker, yielded a c-statistic of 0.96 in the phase 2a study and 0.97 in the phase 2b study. THBS2 data improved the ability of CA19-9 to distinguish PDAC from pancreatitis. With a specificity of 98%, the combination of THBS2 and CA19-9 yielded a sensitivity of 87% for PDAC in the phase 2b study. A THBS2 and CA19-9 blood marker panel measured with a conventional ELISA may improve the detection of patients at high risk for PDAC. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  18. Phase I Trial of a Pathotropic Retroviral Vector Expressing a Cytocidal Cyclin G1 Construct (Rexin-G) in Patients With Advanced Pancreatic Cancer

    PubMed Central

    Galanis, Evanthia; Carlson, Stephanie K; Foster, Nathan R; Lowe, Val; Quevedo, Fernando; McWilliams, Robert R; Grothey, Axel; Jatoi, Aminah; Alberts, Steven R; Rubin, Joseph

    2009-01-01

    Rexin-G is a pathotropic retroviral vector displaying a von Willebrand factor–targeting motif and expressing a dominant negative cyclin G1 gene. We undertook a phase I trial of intravenous (IV) administration of Rexin-G in patients with gemcitabine refractory, metastatic pancreatic adenocarcinoma. Twelve patients were treated. Dose escalation was performed from a dose of 1 × 1011 colony forming units (CFU) per cycle to 6 × 1011 CFU per cycle. The treatment was well tolerated. One dose-limiting toxicity (DLT) at dose level 2 (1.5 × 1011 CFU per cycle) was observed, consisting of grade 3 transaminitis. There was no detection of replication-competent virus in patients’ peripheral blood mononuclear cells (PBMCs) or viral integration in DNA obtained from PBMCs, and no development of neutralizing antibodies. No evidence of antitumor activity was observed. The best objective response was progressive disease in 11 of the 12 study patients, while 1 patient showed radiographically stable disease with clinical deterioration and increase in the CA19.9 tumor marker. Median time to progression was 32 days. The median duration of survival of the study patients was 3.5 months from treatment initiation. Rexin-G is well tolerated in doses up to 6 × 1011 CFU in patients with recurrent pancreatic cancer, but there was no evidence of clinical antitumor activity. PMID:18388964

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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.

  5. 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.

  6. Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis.

    PubMed

    Marson, Fernando Augusto de Lima; Bertuzzo, Carmen Silvia; Ribeiro, Maria Ângela Gonçalves de Oliveira; Ribeiro, Antônio Fernando; Ribeiro, José Dirceu

    2013-01-01

    To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset.

  7. 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

  8. Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.

    PubMed

    Kuo, Hsu-Ping; Ezell, Scott A; Schweighofer, Karl J; Cheung, Leo W K; Hsieh, Sidney; Apatira, Mutiah; Sirisawad, Mint; Eckert, Karl; Hsu, Ssucheng J; Chen, Chun-Te; Beaupre, Darrin M; Versele, Matthias; Chang, Betty Y

    2017-07-01

    Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy. Mol Cancer Ther; 16(7); 1246-56. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. 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...

  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. 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

  12. 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

  13. Uterine fibroids with positive 18F-FDG PET/CT image and significantly increased CA19-9: A case report.

    PubMed

    Ma, Yan; Shao, Xiaonan

    2017-12-01

    Uterine fibroids are the most common pelvic solid tumors and common to 25% of women. F-fluorodexyglucose (F-FDG) is an energy metabolism tracer. Although FDG is generally concentrated in malignant lesions with high glucose metabolism, it can also accumulate in normal tissues, benign lesions, and inflammatory sites. The exact mechanism of FDG uptake by uterine fibroids is not clear. Here, we report a case of uterine fibroids with positive F-FDG positron emission tomography/computed tomography (PET/CT) imaging and significantly increased CA19-9. The patient was a 43-year-old woman and admitted to our hospital because of "1-year-extended menstrual periods." At admission, she had normal CA125, AFP, and CEA level and CA19-9>1000.00 U/mL. Gynecological transvaginal ultrasound found enlarged uterus with an anterior hypoechoic area of 3.9 × 4.2 cm. CT and contrast-enhanced CT showed significantly enhanced mass shadow on the left anterior wall of uterus. F-FDG PET/CT showed increased FDG metabolism of tumor in the anterior wall of the uterus. Laparoscopic hysterectomy was performed. Pathological examination demonstrated subserosal leiomyoma. Her CA19-9 level dropped to 91.50 U/mL 1 day after surgery. Significantly elevated CA19-9 was positioned in the uterus by PET/CT imaging, which not only avoided unnecessary gastrointestinal endoscopy and reduced the suffering of patients, but also strengthened the operation confidence in gynecologists. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  14. 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

  15. 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

  16. 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.

  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. Development of metal organic fromwork-199 immobilized zeolite foam for adsorption of common indoor VOCs.

    PubMed

    Saini, Vipin K; Pires, João

    2017-05-01

    Reticulated foam shaped adsorbents are more efficient for the removal of volatile organic compounds (VOCs), particularly from low VOC-concentration indoor air streams. In this study composite structure of zeolite and metal organic frameworks (MOFs), referred as ZMF, has been fabricated by immobilization of fine MOF-199 powder on foam shaped Zeolite Socony Mobil-5 (ZSM-5) Zeolitic structure, referred as ZF. The ZMF possess a uniform and well-dispersed coating of MOF-199 on the porous framework of ZF. It shows higher surface area, pore volume, and VOCs adsorption capacity, as compared to ZF-structure. Post-fabrication changes in selective adsorption properties of ZMF were studied with three common indoor VOCs (benzene, n-hexane, and cyclohexane), using gravimetric adsorption technique. The adsorption capacity of ZMF with different VOCs follow the order of benzene>n-hexane>cyclohexane. In comparison with MOF-199 and ZF, the composite structure ZMF shows improvement in selectivity for benzene from other two VOCs. Further, improvement in efficiency and stability of prepared ZMF was found to be associated with its high MOF loading capacity and unique morphological and structural properties. The developed composite structure with improved VOCs removal and recyclability could be a promising material for small to limited scale air pollution treatment units. Copyright © 2016. Published by Elsevier B.V.

  19. 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.

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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

  5. Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer.

    PubMed

    Zhao, Yun-Peng; Zhou, Ping-Ting; Ji, Wei-Ping; Wang, Hao; Fang, Meng; Wang, Meng-Meng; Yin, Yue-Peng; Jin, Gang; Gao, Chun-Fang

    2017-02-01

    Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.

  6. 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

  7. 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

  8. HLA-G 14-bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

    PubMed

    Genre, J; Reginaldo, F P Santos; Andrade, J Marco de Leon; Lima, F P; da Camara, A V Coutinho; Donadi, E A; Crispim, J C

    2016-01-01

    H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA-G), a non-classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA-G 14-bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA-G and its genetic polymorphisms in bacterial infection. Sixty-eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA-G 14-bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14-bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection. © 2015 The Foundation for the Scandinavian Journal of Immunology.

  9. 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.

  10. Microwave Observations and Modeling of O2 (1-delta(sub g)) and O3 Diurnal Variation in the Mesosphere

    NASA Technical Reports Server (NTRS)

    Sandor, Brad J.; Clancy, R. Todd; Rusch, David W.; Randall, Cora E.; Eckman, Richard S.; Siskind, David S.; Muhleman, Duane O.

    1997-01-01

    The first microwave measurements of an electronically excited molecular species in the Earth's atmosphere are presented. Local thermodynamic equilibrium (LTE) rotational line emission from mesospheric O2(1-del(sub g)) was observed at a frequency of 255.01794 GHz (lambda is approx. 1.2 mm), employing the National Radio Astronomy Observatory (NRAO) millimeter facility at Kitt Peak, Arizona (32 N, 111 W). The pressure broadened line shapes of the O2(1-del(sub g)) spectra, which were obtained in January and April 1992 and in January and November 1993, are inverted to retrieve O2(1-del(sub g)) mixing profiles over the 50-70 km altitude region. The observed daytime abundances exceed ozone abundances in the lower mesosphere, which are separately retrieved with coincident O3 spectral line (249.7886 GHz) observations. The January and November 1993 observations are binned into 20-60 min time intervals to study O2(1-del(sub g)) diurnal behavior. Derived abundances of O2(1-del(sub g)) between 50 and 70 km for the four observation dates are 9%, 31%, 3%, and 26%, respectively, each +/- 10% higher than predicted, based on the simple photochemistry of lower mesospheric O2(1-del(sub g)). Modeled variation of [O2(1-del(sub g))] with time of day agrees with observed variation in that the observed difference between model and data abundances is constant throughout the daylight hours of each observation date. Model underprediction Of [02(lAg)] is consistent with similar model underprediction of mesospheric [O3]. A perturbation to the photochemical model that forces decreased ozone chemical loss brings brings both model [O3] and [O2(1-del(sub g))] into agreement with the observations. O2(1-del(sub g)) abundances derived from these 1.2 mm observations agree with [O2(1-del(sub g))] values derived from comparable SME observations of the 1.27 micrometers emission, with assumption of a 3880 sec O2(1-del(sub g)) radiative lifetime. The 6800 sec O2(1-del(sub g)) radiative lifetime proposed by

  11. Aceptabilidad del diagnóstico rápido casero para HIV entre hombres gay y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires

    PubMed Central

    Balán, Iván C.; Carballo-Diéguez, Alex; Marone, Rubén O.; Pando, María A.; Barreda, Victoria; Ávila, María M.

    2011-01-01

    Resumen El uso del diagnóstico rápido para HIV en Argentina, así como otros países de Latinoamérica, ha sido limitado hasta el momento. Este trabajo reporta los resultados provenientes de un estudio cualitativo realizado entre hombres gays y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires, Argentina. El objetivo principal del mismo fue conocer las ventajas y desventajas que los hombres G&HSH perciben en relación al diagnóstico rápido casero para HIV. Se realizaron ocho grupos focales con 73 participantes en los cuales se discutió acerca de las ventajas y desventajas del uso de los diagnósticos rápidos. Las respuestas fueron codificadas utilizando un programa para análisis de datos cualitativos (NVivo) y analizadas temáticamente. Los participantes describieron numerosas ventajas sobre el uso del diagnóstico rápido casero, aunque algunos reportaron importantes preocupaciones dentro de las cuales se destaca la posibilidad de impulsos suicidas si alguien recibe un resultado positivo estando solo. En términos generales se observó una gran aceptabilidad para el uso del diagnóstico rápido si el mismo es realizado por personal de salud en lugares acondicionados para este fin. PMID:25284951

  12. Aceptabilidad del diagnóstico rápido casero para HIV entre hombres gay y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires.

    PubMed

    Balán, Iván C; Carballo-Diéguez, Alex; Marone, Rubén O; Pando, María A; Barreda, Victoria; Avila, María M

    2011-03-01

    El uso del diagnóstico rápido para HIV en Argentina, así como otros países de Latinoamérica, ha sido limitado hasta el momento. Este trabajo reporta los resultados provenientes de un estudio cualitativo realizado entre hombres gays y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires, Argentina. El objetivo principal del mismo fue conocer las ventajas y desventajas que los hombres G&HSH perciben en relación al diagnóstico rápido casero para HIV. Se realizaron ocho grupos focales con 73 participantes en los cuales se discutió acerca de las ventajas y desventajas del uso de los diagnósticos rápidos. Las respuestas fueron codificadas utilizando un programa para análisis de datos cualitativos (NVivo) y analizadas temáticamente. Los participantes describieron numerosas ventajas sobre el uso del diagnóstico rápido casero, aunque algunos reportaron importantes preocupaciones dentro de las cuales se destaca la posibilidad de impulsos suicidas si alguien recibe un resultado positivo estando solo. En términos generales se observó una gran aceptabilidad para el uso del diagnóstico rápido si el mismo es realizado por personal de salud en lugares acondicionados para este fin.

  13. 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.

  14. Environmental Assessment for Wing Infrastructure Development Outlook (WINDO) Projects at Holloman Air Force Base, New Mexico

    DTIC Science & Technology

    2005-11-01

    Air Force Base, Alamogordo, New Mexico Li ncol n Cou n ty Si err a Cou n ty Oter o Cou n ty Doñ a A n a Cou n ty Ruidoso Ruidoso Downs Tularosa...Tularosa, New Mexico; US 70 travels northeast through Ruidoso , New Mexico, and US 54 provides access to northern New Mexico. In Las Cruces, US 70

  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

  16. Coinheritance of a novel mutation on the HBA1 gene: c.187delG (p.W62fsX66) [codon 62 (-G) (α1)] with the α212 patchwork allele and Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T].

    PubMed

    Scheps, Karen G; De Paula, Silvia M; Bitsman, Alicia R; Freigeiro, Daniel H; Basack, F Nora; Pennesi, Sandra P; Varela, Viviana

    2013-01-01

    We describe a novel frameshift mutation on the HBA1 gene (c.187delG), causative of α-thalassemia (α-thal) in a Black Cuban family with multiple sequence variants in the HBA genes and the Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T] mutation. The deletion of the first base of codon 62 resulted in a frameshift at amino acid 62 with a putative premature termination codon (PTC) at amino acid 66 on the same exon (p.W62fsX66), which most likely triggers nonsense mediated decay of the resulting mRNA. This study also presents the first report of the α212 patchwork allele in Latin America and the description of two new sequence variants in the HBA2 region (c.-614G>A in the promoter region and c.95+39 C>T on the first intron).

  17. The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia.

    PubMed

    Itchaki, Gilad; Brown, Jennifer R

    2016-10-01

    Venetoclax (VEN, ABT-199/GDC-0199) is an orally bioavailable BH3-mimetic that specifically inhibits the anti-apoptotic B-cell lymphoma/leukemia 2 (BCL2) protein. Although BCL2 overexpression is not genetically driven in chronic lymphocytic leukemia (CLL), it is nearly universal and represents a highly important and prevalent mechanism of apoptosis evasion, making it an attractive therapeutic target. This review summarizes the role of BCL2 in CLL pathogenesis, the development path targeting its inhibition prior to VEN, and the preclinical and clinical data regarding the effectiveness and safety of VEN. We further strive to contextualize VEN in the current CLL treatment landscape and discuss potential mechanisms of resistance.

  18. Evaluation of ascitic soluble human leukocyte antigen-G for distinguishing malignant ascites from benign ascites.

    PubMed

    Sun, Juan; Chang, Yan-Xiang; Niu, Chun-Yan

    2017-11-01

    The overexpression of soluble human leukocyte antigen-G is associated with malignant tumours. The purpose of our study was to detect soluble human leukocyte antigen-G concentrations in ascites and to evaluate the value of ascitic soluble human leukocyte antigen-G for the diagnosis of malignant ascites. Enzyme-linked immunosorbent assay was used to detect soluble human leukocyte antigen-G levels in 64 patients with malignant ascites and 30 patients with benign ascites. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of ascitic soluble human leukocyte antigen-G for the detection of malignant ascites. Ascitic soluble human leukocyte antigen-G levels were significantly higher in the malignant ascites group than in the benign ascites group (20.718 ± 3.215 versus 12.467 ± 3.678 µg/L, t = 7.425, p < 0.001). The area under the receiver operating characteristic curve for ascitic soluble human leukocyte antigen-G was 0.957 (95% confidence interval, 0.872-0.992). At a cut-off value of 19.60 µg/L, the sensitivity and specificity of ascitic soluble human leukocyte antigen-G were 87.5% (95% confidence interval, 71.0%-96.5%) and 100% (95% confidence interval, 88.4%-100%), respectively. With respect to area under the receiver operating characteristic curve, sensitivity and specificity, ascitic carcinoembryonic antigen (0.810, 68.75% and 83.33%, respectively) and carbohydrate antigen 19-9 (0.710, 65.63% and 70%, respectively) significantly differed (all p < 0.05). In malignant ascites that were cytology-negative and biopsy-positive, the rate of positivity for ascitic soluble human leukocyte antigen-G was 75%, which was higher than the corresponding rates for ascitic carcinoembryonic antigen (31.25%) and carbohydrate antigen 19-9 (6.25%; both p < 0.05). In conclusion, The detection of ascitic soluble human leukocyte antigen-G exhibited good performance for diagnosing malignant ascites, and particularly those that

  19. Effects of antibodies to phosphorylated and non-phosphorylated tau on in vitro tau phosphorylation at Serine-199: Preliminary report.

    PubMed

    Loeffler, David A; Smith, Lynnae M; Klaver, Andrea C; Martić, Sanela

    2015-07-01

    Phosphorylation of multiple amino acids on tau protein ("hyperphosphorylation") is required for the development of tau pathology in Alzheimer's disease. Administration of anti-tau antibodies to transgenic "tauopathy mice" has been shown to reduce their tau pathology but the mechanisms responsible are unclear. To examine the effects of anti-tau antibodies on tau phosphorylation, we used western blots to study the effects of three antibodies to phosphorylated tau (pTau), namely anti-pTau S199, T231, and S396, and three antibodies to non-phosphorylated tau on in vitro phosphorylation of recombinant human tau-441 at S199. Inclusion of an anti-pTau T231 antibody in the phosphorylation reaction reduced the intensity of monomeric pTau S199 in western blots of denaturing gels, but the other antibodies had no apparent effects on this process. Surprisingly, including all three anti-phospho-tau antibodies in the reaction did not reduce the intensity of the monomer band, possibly due to steric hindrance between the antibodies. These preliminary findings suggest that anti-tau antibodies may have minimal direct effects on tau phosphorylation. Limitations of using western blots to examine the effects of anti-tau antibodies on this process were found to include between-experiment variability in pTau band densities and poor resolution of high molecular weight pTau oligomers. The presence of bands representing immunoglobulins as well as pTau may also complicate interpretation of the western blots. Further studies are indicated to examine the effects of anti-pTau antibodies on phosphorylation of other tau amino acids in addition to S199. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. The Role of PAI-1 4G/5G Promoter Polymorphism and Its Levels in the Development of Ischemic Stroke in Young Indian Population.

    PubMed

    Akhter, Mohammad Suhail; Biswas, Arijit; Abdullah, Saleh Mohammed; Behari, Madhuri; Saxena, Renu

    2017-11-01

    The plasminogen activator inhibitor-1 (PAI-1) gene has been found to be associated with the pathogenesis and progression of vascular diseases including stroke. A 4G/5G, PAI-1 gene polymorphism has been found to be associated with the plasma PAI-1 levels in different ethnic populations but results are still controversial. The aim of this study was to determine the potential association of 4G/5G polymorphism and plasma PAI-1 levels in the development of ischemic stroke (IS) in young Asian Indians. One hundred patients with IS and an equal number of age- and sex-matched controls were studied. The 4G/5G polymorphism was genotyped in the study population through allele-specific polymerase chain reaction. Plasma PAI-1 levels were evaluated using a commercial kit. The PAI-1 levels were significantly higher in patients when compared to the controls ( P = .03). The variant 4G allele for the PAI-I 4G/5G polymorphism showed both genotypic ( P = .0013, χ 2 = 10.303; odds ratio [OR] = 3.75) as well as allelic association ( P = .0004, χ 2 = 12.273; OR = 1.99) with IS. The homozygous variant 4G/4G also was found to be associated with the higher PAI-1 levels (0.005). The variant allele 4G of PAI-1 4G/5G polymorphism and higher plasma PAI-1 levels were found to be significantly associated with IS in young Asian Indians.

  1. 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.

  2. A novel classifier based on three preoperative tumor markers predicting the cancer-specific survival of gastric cancer (CEA, CA19-9 and CA72-4).

    PubMed

    Guo, Jing; Chen, Shangxiang; Li, Shun; Sun, Xiaowei; Li, Wei; Zhou, Zhiwei; Chen, Yingbo; Xu, Dazhi

    2018-01-12

    Several studies have highlighted the prognostic value of the individual and the various combinations of the tumor markers for gastric cancer (GC). Our study was designed to assess establish a new novel model incorporating carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4). A total of 1,566 GC patients (Primary cohort) between Jan 2000 and July 2013 were analyzed. The Primary cohort was randomly divided into Training set (n=783) and Validation set (n=783). A three-tumor marker classifier was developed in the Training set and validated in the Validation set by multivariate regression and risk-score analysis. We have identified a three-tumor marker classifier (including CEA, CA19-9 and CA72-4) for the cancer specific survival (CSS) of GC (p<0.001). Consistent results were obtained in the both Training set and Validation set. Multivariate analysis showed that the classifier was an independent predictor of GC (All p value <0.001 in the Training set, Validation set and Primary cohort). Furthermore, when the leave-one-out approach was performed, the classifier showed superior predictive value to the individual or two of them (with the highest AUC (Area Under Curve); 0.618 for the Training set, and 0.625 for the Validation set), which ascertained its predictive value. Our three-tumor marker classifier is closely associated with the CSS of GC and may serve as a novel model for future decisions concerning treatments.

  3. [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.

  4. The Failure Models of Lead Free Sn-3.0Ag-0.5Cu Solder Joint Reliability Under Low-G and High-G Drop Impact

    NASA Astrophysics Data System (ADS)

    Gu, Jian; Lei, YongPing; Lin, Jian; Fu, HanGuang; Wu, Zhongwei

    2017-02-01

    The reliability of Sn-3.0Ag-0.5Cu (SAC 305) solder joint under a broad level of drop impacts was studied. The failure performance of solder joint, failure probability and failure position were analyzed under two shock test conditions, i.e., 1000 g for 1 ms and 300 g for 2 ms. The stress distribution on the solder joint was calculated by ABAQUS. The results revealed that the dominant reason was the tension due to the difference in stiffness between the print circuit board and ball grid array, and the maximum tension of 121.1 MPa and 31.1 MPa, respectively, under both 1000 g or 300 g drop impact, was focused on the corner of the solder joint which was located in the outmost corner of the solder ball row. The failure modes were summarized into the following four modes: initiation and propagation through the (1) intermetallic compound layer, (2) Ni layer, (3) Cu pad, or (4) Sn-matrix. The outmost corner of the solder ball row had a high failure probability under both 1000 g and 300 g drop impact. The number of failures of solder ball under the 300 g drop impact was higher than that under the 1000 g drop impact. The characteristic drop values for failure were 41 and 15,199, respectively, following the statistics.

  5. Genomic sequence of Heliothis virescens ascovirus 3g isolated from Spodoptera exigua.

    PubMed

    Huang, Guo-Hua; Wang, Yun-Sheng; Wang, Xing; Garretson, Tyler A; Dai, Liang-Ying; Zhang, Chuan-Xi; Cheng, Xiao-Wen

    2012-11-01

    Heliothis virescens ascovirus 3a (HvAV-3a), a member of the family Ascoviridae, has the highest diversity among ascovirus species that have been reported in Australia, Indonesia, China, and the United States. To understand the diversity and origin of this important ascovirus, the complete genome of the HvAV Indonesia strain (HvAV-3g), isolated from Spodoptera exigua, was determined to be 199,721 bp, with a G+C content of 45.9%. Therefore, HvAV-3g has the largest genome among the reported ascovirus genomes to date. There are 194 predicted open reading frames (ORFs) encoding proteins of 50 or more amino acid residues. In comparison to HvAV-3e reported from Australia, HvAV-3g has all the ORFs in HvAV-3e with 6 additional ORFs unique to HvAV-3g, including 1 peptidase C26 gene with the highest identity to Drosophila spp. and 2 gas vesicle protein U (GvpU) genes with identities to Bacillus megaterium. The five unique homologous regions (hrs) and 25 baculovirus repeat ORFs (bro) of HvAV-3g are highly variable.

  6. 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.

  7. Conservacion de truchas del Pacifico

    Treesearch

    Brooke E. Penaluna

    2016-01-01

    La historia de las truchas del Pacífico, pertenecientes al género Oncorhynchus, es una historia muy interesante que se basa en la persistencia y diversificación de sus especies debido, en gran parte, al dinamismo propio que existe en su medio ambiente. Desde el oeste de Norteamérica, extendiéndose hasta el este de Asia, las truchas del Pacífico han experimentado la...

  8. Mumps outbreaks in a highly vaccinated population: Investigation of a neutralization titre against the current circulating wildtype genotype G5 mumps virus.

    PubMed

    Kenny, Lena; O'Kelly, Edwin; Connell, Jeff; De Gascun, Cillian; Hassan, Jaythoon

    2016-01-01

    Mumps outbreaks continue to occur globally, despite high levels of uptake of the mumps vaccine. In order to address immunity to the current circulating wildtype virus, we sought to determine a mumps G5 specific IgG quantitative value which correlates with genotype G5 specific neutralization ability in vitro. Sera from 199 individuals including controls and acute mumps cases were assessed for mumps specific IgG titres using five different enzyme immunoassays coated with antigen from different mumps virus strains. A subset of 66 sera was also assessed for in vitro neutralizing antibody against a contemporary circulating genotype G5 mumps virus. For all the different antigenic targets, mumps specific IgG titres were higher in patients following acute mumps infection compared to controls. In acute mumps infected patients, females showed significantly higher serum titres of anti-G5 IgG compared to males (p<0.05). Furthermore, control males did not show any change in G5 specific IgG with increasing age whereas females show a progressive rise in titre. Linear regression analysis revealed a significant association between the mumps G5 specific IgG levels in the EIA and the in vitro neutralization titres (r(2)=0.59). Specific IgG to the current circulating genotype G5 mumps strain showed significantly lower titres in males which supports our previous observation that there is a male gender bias in cases of acute mumps infection. Furthermore, in this preliminary study, the data indicate that genotype G5 specific IgG levels of >40 RU/ml are required for neutralization capability to be observed in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 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.

  10. 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.

  11. Wave maps from Gödel's universe

    NASA Astrophysics Data System (ADS)

    Barletta, Elisabetta; Dragomir, Sorin; Magliaro, Marco

    2014-10-01

    Using a result by Koch (1988 Trans. Am. Math. Soc. 307 827-41) we realize Gödel's universe G_{α }^{4}=({{{R}}^{4}},{{g}_{α}}) as the total space of a principal {R}-bundle over a strictly pseudo-convex CR manifold M3 and exploit the analogy between {{g}_{Yalpha;}} and Fefferman's metric {{F}_{θ}} (Fefferman 1976 Ann. Math. 103 395-416 104 393-4) to show that for any {R}-invariant wave map Φ of G_{α}^{4} into a Riemannian manifold N, the corresponding base map φ :{{M}^{3}}\\to N is subelliptic harmonic, with respect to a canonical choice of contact form θ on M3. We show that the subelliptic Jacobi operator J_{b}^{φ} of ϕ has a discrete Dirichlet spectrum on any bounded domain D\\subset {{M}^{3}} supporting the Poincaré inequality on \\mathop{W}\\limits^{\\circ }{}_{H}^{1,2}(D,{{φ}^{-1}}TN) and Kondrakov compactness, i.e. compactness of the embedding \\mathop{W}\\limits^{\\circ }{}_{H}^{1,2}(D,{{φ }^{-1}}TN)\\hookrightarrow {{L}^{2}}(D,{{φ}^{-1}}TN). We exhibit an explicit solution π :G_{α}^{4}\\to {{M}^{3}} to the wave map system on G_{α}^{4}, of index in{{d}^{Ω}}(π)\\geqslant 1 for any bounded domain Ω \\subset G_{α}^{4}. Mounoud's distance (Mounoud 2001 Differ. Geom. Appl. 15 47-57) d_{{{G}_{0}}, Ω }^{∞}({{g}_{α }}, {{F}_{θ}}) is bounded below by a constant depending only on the rotation frequency of Gödel's universe, thus giving a measure of the bias of {{g}_{α}} from being Fefferman like in the region Ω \\subset {{{R}}^{4}}.

  12. Etnografía acelerada para transformar normas sociales sobre género y sexualidad en hombres puertorriqueños heterosexuales1,2

    PubMed Central

    Ortiz-Torres, Blanca; Rivera-Ortiz, Rafael J.; Mendoza, Sigrid

    2014-01-01

    Resumen La construcción de roles de género dominantes contribuyen al riesgo de contraer VIH, y por tal razón se ha urgido a que se integren las normas sociales relativas al género en las intervenciones preventivas del VIH. Este estudio pretende adaptar y desarrollar una intervención que facilite la transformación de normas sociales del género y de prácticas sexuales en hombres puertorriqueños. La intervención propone transformar normas sociales relacionadas al género y sexualidad en barras comunitarias utilizando el modelo de líderes de opinión. Luego de ser elegidos/as, los/as líderes de opinión diseminan mensajes integrando la importancia de relaciones equitativas entre parejas para la prevención del VIH. La primera fase de esta intervención es discutida en este artículo, la cual incluye un proceso de etnografía acelerada para identificar los escenarios comunitarios en los que podemos desarrollar esta intervención y permitirnos entender la cultura de las barras comunitarias. A partir de las observaciones etnográficas, pudimos: desarrollar un protocolo de seguridad para realizar las observaciones, desarrollar un perfil de la cultura de las barras, elegir las barras a participar en las dos condiciones del estudio y adaptar los instrumentos de la intervención para que respondieran a la particularidad de los/as participantes. PMID:25530828

  13. 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.

  14. TH-B-204-03: TG-199: Implanted Markers for Radiation Treatment Verification

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

    Wang, Z.

    Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRImore » compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a

  15. The Frequency of c.550delA Mutation of the CANP3 Gene in the Polish LGMD2A Population.

    PubMed

    Dorobek, Małgorzata; Ryniewicz, Barbara; Kabzińska, Dagmara; Fidziańska, Anna; Styczyńska, Maria; Hausmanowa-Petrusewicz, Irena

    2015-11-01

    Limb girdle muscular dystrophy 2A (LGMD2A) is the most frequent LGMD variant in the European population, representing about 40% of LGMD. The c.550delA mutation in the CANP3 (calcium activated neutral protease 3) gene is the most commonly reported mutation in LGMD2A. Prevalence of this mutation in the Polish population has not been previously investigated. The aim of this study was to identify and estimate the frequency of the c.550delA mutation in Polish LGMD2A patients. Polymerase chain reaction-sequencing analysis, restriction fragment length polymorphism polymerase chain reaction method. We analyzed 76 families affected with LGMD and identified 62 probands with mutations in the CANP3 gene. C.550delA was the most common mutation identified, being found in 78% of the LGMD2A families. The remaining mutations observed multiple times were as follows: c.598-612del15ntd; c.2242C>T; c.418dupC; c.1356insT, listed in terms of decreasing frequency. Two novel variants in the CANP3 gene, that is, c.700G>A Gly234Arg and c.661G>A Gly221Ser were also characterized. Overall, mutations in the LGMD2A gene were estimated to be present in 81% of patients with the LGMD phenotype who were without sarcoglycans and dysferlin deficiency on immunocytochemical analysis. The frequency of the heterozygous c.550delA mutation in the healthy Polish population was estimated at 1/124. The c.550delA is the most frequent CANP3 mutation in the Polish population, thus sequencing of exon 4 of this gene could identify the majority of LGMD2A patients in Poland.

  16. Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

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

    Yoo, Tae; Lee, Woo Jin; Woo, Sang Myung

    2011-11-15

    Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM{sup 3m}), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, andmore » CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM{sup 3m}, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2-31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM{sup 3m} occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level ({<=}400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM{sup 3m} (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p < 0.05 for all three parameters). Conclusion: For patients with localized and unresectable pancreatic cancer, pretreatment CA 19-9 level could be helpful in predicting tumor response, DM{sup 3m}, and overall survival and identifying patients who will benefit from CRT.« less

  17. Search for an Electric Dipole Moment (EDM) of 199Hg

    NASA Astrophysics Data System (ADS)

    Heckel, Blayne

    2017-04-01

    The observation of a non-zero EDM of an atom or elementary particle, at current levels of experimental sensitivity, would imply CP violation beyond the CKM matrix of the standard model of particle physics. Additional sources of CP violation have been proposed to help explain the excess of matter over anti-matter in our universe and the magnitude of ΘQCD, the strength of CP violation in the strong interaction, remains unknown. We have recently completed a set of measurements on the EDM of 199Hg, sensitive to both new sources of CP violation and ΘQCD. The experiment compares the phase accumulated by precessing Hg spins in vapor cells with electric fields parallel and anti-parallel to a common magnetic field. Our new result represents a factor of 5 improvement over previous results. A description of the EDM experiment, data, systematic error considerations will be presented. This work was supported by NSF Grant No. 1306743 and by the DOE Office of Nuclear Physics under Award No. DE-FG02-97ER41020.

  18. Association between endothelial nitric oxide synthase (ENOS) G894T polymorphism and high altitude (HA) adaptation: a meta-analysis.

    PubMed

    Lu, Hong-xiang; Wang, Yu-xiao; Chen, Yu; Luo, Yong-jun

    2015-11-01

    Highland natives adapt well to the hypoxic environment at high altitude (HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial ni- tric oxide synthase (ENOS) G894T polymorphism contributed to the physiology and pathophysiology of hu- mans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894T polymorphism and HA adaptation through analyzing the published data. We searched all relevant literature about the ENOS G894T polymorphism and HA adaptation in PubMed, Med- line, and Embase before Step 2015. A random-effects model was applied (Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups (OR = 1.85; 95% Cl, 1.47-2.33; P < 0.0001). In addition, the GG genotype was significantly associated with HA adaptation (OR = 1.99; 95% Cl, 1.54-2.57; P < 0.0001). Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.

  19. A (201)Hg+ Comagnetometer for (199)Hg+ Trapped Ion Space Atomic Clocks

    NASA Technical Reports Server (NTRS)

    Burt, Eric A.; Taghavi, Shervin; Tjoelker, Robert L.

    2011-01-01

    A method has been developed for unambiguously measuring the exact magnetic field experienced by trapped mercury ions contained within an atomic clock intended for space applications. In general, atomic clocks are insensitive to external perturbations that would change the frequency at which the clocks operate. On a space platform, these perturbative effects can be much larger than they would be on the ground, especially in dealing with the magnetic field environment. The solution is to use a different isotope of mercury held within the same trap as the clock isotope. The magnetic field can be very accurately measured with a magnetic-field-sensitive atomic transition in the added isotope. Further, this measurement can be made simultaneously with normal clock operation, thereby not degrading clock performance. Instead of using a conventional magnetometer to measure ambient fields, which would necessarily be placed some distance away from the clock atoms, first order field-sensitive atomic transition frequency changes in the atoms themselves determine the variations in the magnetic field. As a result, all ambiguity over the exact field value experienced by the atoms is removed. Atoms used in atomic clocks always have an atomic transition (often referred to as the clock transition) that is sensitive to magnetic fields only in second order, and usually have one or more transitions that are first-order field sensitive. For operating parameters used in the (199)Hg(+) clock, the latter can be five orders of magnitude or more sensitive to field fluctuations than the clock transition, thereby providing an unambiguous probe of the magnetic field strength.

  20. Analysis of the irradiation data for A302B and A533B correlation monitor materials

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

    Wang, J.A.

    1996-04-01

    The results of Charpy V-notch impact tests for A302B and A533B-1 Correlation Monitor Materials (CMM) listed in the surveillance power reactor data base (PR-EDB) and material test reactor data base (TR-EDB) are analyzed. The shift of the transition temperature at 30 ft-lb (T{sub 30}) is considered as the primary measure of radiation embrittlement in this report. The hyperbolic tangent fitting model and uncertainty of the fitting parameters for Charpy impact tests are presented in this report. For the surveillance CMM data, the transition temperature shifts at 30 ft-lb ({Delta}T{sub 30}) generally follow the predictions provided by Revision 2 of Regulatorymore » Guide 1.99 (R.G. 1.99). Difference in capsule temperatures is a likely explanation for large deviations from R.G. 1.99 predictions. Deviations from the R.G. 1.99 predictions are correlated to similar deviations for the accompanying materials in the same capsules, but large random fluctuations prevent precise quantitative determination. Significant scatter is noted in the surveillance data, some of which may be attributed to variations from one specimen set to another, or inherent in Charpy V-notch testing. The major contributions to the uncertainty of the R.G. 1.99 prediction model, and the overall data scatter are from mechanical test results, chemical analysis, irradiation environments, fluence evaluation, and inhomogeneous material properties. Thus in order to improve the prediction model, control of the above-mentioned error sources needs to be improved. In general the embrittlement behavior of both the A302B and A533B-1 plate materials is similar. There is evidence for a fluence-rate effect in the CMM data irradiated in test reactors; thus its implication on power reactor surveillance programs deserves special attention.« less

  1. Differentiating immunoglobulin g4-related sclerosing cholangitis from hilar cholangiocarcinoma.

    PubMed

    Tabata, Taku; Kamisawa, Terumi; Hara, Seiichi; Kuruma, Sawako; Chiba, Kazuro; Kuwata, Go; Fujiwara, Takashi; Egashira, Hideto; Koizumi, Koichi; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Itoi, Takao

    2013-03-01

    Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. In patients with hilar CC, obstructive jaundice was more frequent (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were significantly higher and frequently elevated. The pancreas was enlarged in all IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01). Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC patients (p<0.01). Bile duct wall thickening in areas without stenosis was more frequent in IgG4-SC patients (p<0.01). An integrated diagnostic approach based on clinical, serological, imaging, and histological findings is necessary to differentiate IgG4-SC from hilar CC.

  2. Differentiating Immunoglobulin G4-Related Sclerosing Cholangitis from Hilar Cholangiocarcinoma

    PubMed Central

    Tabata, Taku; Hara, Seiichi; Kuruma, Sawako; Chiba, Kazuro; Kuwata, Go; Fujiwara, Takashi; Egashira, Hideto; Koizumi, Koichi; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Itoi, Takao

    2013-01-01

    Background/Aims Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. Methods We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. Results In patients with hilar CC, obstructive jaundice was more frequent (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were significantly higher and frequently elevated. The pancreas was enlarged in all IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01). Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC patients (p<0.01). Bile duct wall thickening in areas without stenosis was more frequent in IgG4-SC patients (p<0.01). Conclusions An integrated diagnostic approach based on clinical, serological, imaging, and histological findings is necessary to differentiate IgG4-SC from hilar CC. PMID:23560161

  3. Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion.

    PubMed

    Tsibulnikov, S Yu; Maslov, L N; Mukhomedzyanov, A V; Krylatov, A V; Tsibulnikova, M R; Lishmanov, Yu B

    2015-10-01

    We studied the ability of the agonist of κ1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and κ-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before reperfusion 2-fold reduced the ratio of infarction to risk area. Administration of ICI 199,441 in a dose of 0.1 mg/kg 15 min before ischemia produced a potent antiarrhythmic effect. Antiarrhythmic effect of κ-opioid receptor agonists depended on activation of κ-opioid receptors.

  4. Cu@C nanoporous composites containing little copper oxides derived from dimethyl imidazole modified MOF199 as electrocatalysts for hydrogen evolution reaction

    NASA Astrophysics Data System (ADS)

    Wei, Xuedong; Li, Na; Zhang, Xianming

    2017-12-01

    It remains a huge challenge to develop non precious electrocatalysts with high activity to substitute commercial Pt catalysts for hydrogen evolution reactions (HER). Here, the C-Cu-DI and C-Cu materials with the copper based nanoporous carbon structures were synthesized by carbonizing MOF199 and DI-MOF199. The composite structure and HER electrocatalytic properties of the C-Cu-DI and C-Cu materials are studied. The results show that C-Cu-DI and C-Cu samples exhibit good catalytic activity. And C-Cu-DI sample through the addition of Dimethyl imidazole(DI) in the DI-MOF199 precursor has higher electrocatalytic activity than the C-Cu sample. The superior catalytic activity is attributed to the special composite structure of nanoscale deposition particles on the framework with plenty of nano pores and nano copper and few copper oxidation particles distributed or wrapped into the amorphous porous carbon phase. The nano copper and few copper oxidation particles in the C-Cu and C-Cu-DI catalysts maybe provide the more effective catalytic activity sites. The C-Cu-DI composite with large size spherical hollow deposition particles has higher conductivity, better BET surface area and reasonable micro-meso-macro porous distribution, so the overpotentials at the current density of 1 mA cm-2 and 10 mA cm-2 are respectively 270 mV and 390 mV vs. RHE. Although the HER activity has a big gap with commercial platinum catalyst, this study can provide an important experimental exploration for the design of copper based non noble metal/nano porous carbon composite HER electrocatalyst.

  5. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions.

    PubMed

    Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

    2016-02-24

    Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug-drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug-drug interactions.

  6. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug–Drug Interactions

    PubMed Central

    Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

    2016-01-01

    Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug–drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug–drug interactions. PMID:26927160

  7. 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...

  8. TH-B-204-00: Implanted Markers for Radiation Therapy and TG 199 Update

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

    NONE

    Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRImore » compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a

  9. A Trapped Mercury 199 Ion Frequency Standard

    DTIC Science & Technology

    1981-12-01

    ing resul t t h a t could possibly be explained by a for tu i t ious cancel la t ion of t w o e f f ec t s : t h e second order doppler...h a t t h e helium cooling is e f f ec t ive . O the r e f f e c t s of t he helium include nar rower l ines and a la rger s ignal indicat...Desaintfuscien, K. Barjllet, J . Viennet, P. Pet i t , and C. Audoin, Appl. Phys. 24, 107 (1981). 4. R, Ifflaender and G. Werth; Metrologia 13, 167 (1977

  10. Comparison of leaf proteomes of cassava (Manihot esculenta Crantz) cultivar NZ199 diploid and autotetraploid genotypes.

    PubMed

    An, Feifei; Fan, Jie; Li, Jun; Li, Qing X; Li, Kaimian; Zhu, Wenli; Wen, Feng; Carvalho, Luiz J C B; Chen, Songbi

    2014-01-01

    Cassava polyploid breeding has drastically improved our knowledge on increasing root yield and its significant tolerance to stresses. In polyploid cassava plants, increases in DNA content highly affect cell volumes and anatomical structures. However, the mechanism of this effect is poorly understood. The purpose of the present study was to compare and validate the changes between cassava cultivar NZ199 diploid and autotetraploid at proteomic levels. The results showed that leaf proteome of cassava cultivar NZ199 diploid was clearly differentiated from its autotetraploid genotype using 2-DE combined MS technique. Sixty-five differential protein spots were seen in 2-DE image of autotetraploid genotype in comparison with that of diploid. Fifty-two proteins were identified by MALDI-TOF-MS/MS, of which 47 were up-regulated and 5 were down-regulated in autotetraploid genotype compared with diploid genotype. The classified functions of 32 up-regulated proteins were associated with photosynthesis, defense system, hydrocyanic acid (HCN) metabolism, protein biosynthesis, chaperones, amino acid metabolism and signal transduction. The remarkable variation in photosynthetic activity, HCN content and resistance to salt stress between diploid and autotetraploid genotypes is closely linked with expression levels of proteomic profiles. The analysis of protein interaction networks indicated there are direct interactions between the 15 up-regulation proteins involved in the pathways described above. This work provides an insight into understanding the protein regulation mechanism of cassava polyploid genotype, and gives a clue to improve cassava polyploidy breeding in increasing photosynthesis and resistance efficiencies.

  11. Soluble HLA-G in pregnancies complicated by autoimmune rheumatic diseases.

    PubMed

    Beneventi, Fausta; Badulli, Carla; Locatelli, Elena; Caporali, Roberto; Ramoni, Véronique; Cavagnoli, Chiara; Simonetta, Margherita; Garbin, Giulia; Tinelli, Carmine; Alpini, Claudia; Montecucco, CarloMaurizio; Martinetti, Miryam; Spinillo, Arsenio

    2015-08-01

    Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p<0.001) was found between the maternal and fetal titers of ANA autoantibodies as well as between maternal and fetal sHLAG circulating levels (r=0.58 and r=0.67, respectively, for controls and cases, p<0.001). Maternal s-HLA-G blood concentrations were significantly higher in subjects with rheumatic disease DEL/DEL homozygous for a polymorphism of the 3' untranslated regulatory region of HLA-G (HLA-G 14bp) than in the corresponding healthy controls (mean values 141.5ng/ml [SD: 166] vs 54.2ng/ml [SD: 35], p=0.009). Increasing maternal and cord blood levels of s-HLA-G concentrations among pregnant subjects with rheumatic diseases compared with controls suggest that autoimmune diseases prompt a maternal and fetal immune response that favors pregnancy immune tolerance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. 57. G.M.W., photographer March 26, 1940 HUMBOLDT COUNTY, SECTION K, ...

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

    57. G.M.W., photographer March 26, 1940 HUMBOLDT COUNTY, SECTION K, HIGHWAY 1. HUM-1-K #93, STA. 255, 3-26-40, G.M.W. Stamped office copy. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  13. Static Longitudinal Stability and Control Characteristics At A Mach Number of 1.99 of a Lenticular-Shaped Reentry Vehicle

    NASA Technical Reports Server (NTRS)

    Jackson, Charles M., Jr.; Harris, Roy V., Jr.

    1960-01-01

    An investigation has been made in the Langley 4- by 4-foot supersonic pressure tunnel at a Mach number of 1.99 to determine the longitudinal stability and control characteristics of a reentry model consisting of a lenticular-shaped body with two fin configurations (horizontal fins with end plates). Effects of deflecting the larger size fins as pitch-control surfaces were also investigated. The results indicate that the body alone was unstable from an angle of attack of 0 deg to about 55 deg where it became stable and remained so to 90 deg. The addition of fins provided positive longitudinal stability throughout the angle-of-attack range and increased the lift-drag ratio of the configuration. Reducing the horizontal-fin area at the inboard trailing edge of the fin had only a small effect on the aerodynamic characteristics of the vehicle for the condition of no fin deflection. Deflecting the fins, appeared to be an effective means of pitch control and had only a small effect on lift-drag ratio.

  14. Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: A case report of sustained hematologic response following an abbreviated exposure

    PubMed Central

    2010-01-01

    Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of ~50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide. PMID:20416051

  15. Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure.

    PubMed

    Quddus, Fahd; Clima, Jessica; Seedham, Helen; Sajjad, Ghulam; Galili, Naomi; Raza, Azra

    2010-04-23

    Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of approximately 50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.

  16. Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia.

    PubMed

    Shivakumar, Venkataram; Debnath, Monojit; Venugopal, Deepthi; Rajasekaran, Ashwini; Kalmady, Sunil V; Subbanna, Manjula; Narayanaswamy, Janardhanan C; Amaresha, Anekal C; Venkatasubramanian, Ganesan

    2018-07-01

    Converging evidence suggests important implications of immuno-inflammatory pathway in the risk and progression of schizophrenia. Prenatal infection resulting in maternal immune activation and developmental neuroinflammation reportedly increases the risk of schizophrenia in the offspring by generating pro-inflammatory cytokines including IL-6. However, it is not known how prenatal infection can induce immuno-inflammatory responses despite the presence of immuno-inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the present study was aimed at examining the correlation between 14 bp Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR amplification/direct sequencing and IL-6 gene expression was quantified by using real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We observed significantly low IL6 gene expression in the peripheral mononuclear cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G 14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004) than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it can be assumed that HLA-G and cytokine interactions might play an important role in the immunological underpinnings of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Complete Sequence of a 184-Kilobase Catabolic Plasmid from Sphingomonas aromaticivorans F199†

    PubMed Central

    Romine, Margaret F.; Stillwell, Lisa C.; Wong, Kwong-Kwok; Thurston, Sarah J.; Sisk, Ellen C.; Sensen, Christoph; Gaasterland, Terry; Fredrickson, Jim K.; Saffer, Jeffrey D.

    1999-01-01

    The complete 184,457-bp sequence of the aromatic catabolic plasmid, pNL1, from Sphingomonas aromaticivorans F199 has been determined. A total of 186 open reading frames (ORFs) are predicted to encode proteins, of which 79 are likely directly associated with catabolism or transport of aromatic compounds. Genes that encode enzymes associated with the degradation of biphenyl, naphthalene, m-xylene, and p-cresol are predicted to be distributed among 15 gene clusters. The unusual coclustering of genes associated with different pathways appears to have evolved in response to similarities in biochemical mechanisms required for the degradation of intermediates in different pathways. A putative efflux pump and several hypothetical membrane-associated proteins were identified and predicted to be involved in the transport of aromatic compounds and/or intermediates in catabolism across the cell wall. Several genes associated with integration and recombination, including two group II intron-associated maturases, were identified in the replication region, suggesting that pNL1 is able to undergo integration and excision events with the chromosome and/or other portions of the plasmid. Conjugative transfer of pNL1 to another Sphingomonas sp. was demonstrated, and genes associated with this function were found in two large clusters. Approximately one-third of the ORFs (59 of them) have no obvious homology to known genes. PMID:10049392

  18. 59. V.H.G., photographer October 27, 1948 EUREKA, HUMBOLDT COUNTY, HIGHWAY ...

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

    59. V.H.G., photographer October 27, 1948 EUREKA, HUMBOLDT COUNTY, HIGHWAY 1. HUM-1-EUR #59, LOOKING NORTH BROADWAY & CEDAR, 10-27-48, V.H.G. Stamped office copy. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  19. 58. V.H.G., photographer October 27, 1948 EUREKA, HUMBOLDT COUNTY, HIGHWAY ...

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

    58. V.H.G., photographer October 27, 1948 EUREKA, HUMBOLDT COUNTY, HIGHWAY 1. HUM-1-EUR #60, LOOKING SOUTH, BROADWAY & CLARK, 10-27-48, V.H.G. Stamped office copy. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  20. Comparison of LUMIPULSE(®) G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers.

    PubMed

    Marlet, Julien; Bernard, Maguy

    2016-01-01

    Tumor marker measurements are becoming essential for prognosis and follow-up of patients in oncology. In this context, we aimed to compare a new analyzer, Lumipulse(®) G1200 (Fujirebio group, distributed in Europe by the Innogenetics group) with Kryptor(®) (Thermo Fisher Scientific B.R.A.H.M.S, Asnières, France) and Modular(®) Elecsys E170 (Roche Diagnostics, Meylan, France) for the measurement of seven tumor markers: PSA, AFP, CEA, CA 15-3, CA 125, CA 19-9, and Cyfra 21-1. A total of 471 serum samples from patients with elevated tumor markers and 100 serum from healthy patients were analyzed with Lumipulse(®) G1200 and either Kryptor(®) (for AFP) or Modular(®) (for the six other markers). The good precision of Lumipulse(®) G1200 assays was confirmed with CVs < 2.5% and < 5.0%, obtained, respectively, for within-run imprecision and intermediate imprecision (except for Cyfra 21-1: CV < 13%). For all markers, Lumipulse results were well correlated with Modular or Kryptor results (r ≥ 0.94). Concordance of results interpretation was > 95% and tumor marker kinetics were all similar. We confirmed the analytical performances of Lumipulse(®) tumor marker assays except for the CYFRA 21-1 assay for which performances were poor in this study. We noticed a few discrepancies for the CEA assay. Besides, values obtained for CA 19-9 were higher with Lumipulse leading to a bias (slope = 1.5). But for the four other tumor markers assays (PSA, AFP, CA 125, CA 15-3), the results were directly transferable between Lumipulse and Kryptor or Modular, thus facilitating an eventual substitution of one system by another. © 2014 Wiley Periodicals, Inc.

Some links on this page may take you to non-federal websites. Their policies may differ from this site.