Science.gov

Sample records for specification release procedure

  1. 19 CFR 142.48 - Release procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Release procedure. 142.48 Section 142.48 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.48 Release procedure. (a) General. When the Customs officer...

  2. Guidelines for testing and release procedures

    NASA Technical Reports Server (NTRS)

    Molari, R.; Conway, M.

    1984-01-01

    Guidelines and procedures are recommended for the testing and release of the types of computer software efforts commonly performed at NASA/Ames Research Center. All recommendations are based on the premise that testing and release activities must be specifically selected for the environment, size, and purpose of each individual software project. Guidelines are presented for building a Test Plan and using formal Test Plan and Test Care Inspections on it. Frequent references are made to NASA/Ames Guidelines for Software Inspections. Guidelines are presented for selecting an Overall Test Approach and for each of the four main phases of testing: (1) Unit Testing of Components, (2) Integration Testing of Components, (3) System Integration Testing, and (4) Acceptance Testing. Tools used for testing are listed, including those available from operating systems used at Ames, specialized tools which can be developed, unit test drivers, stub module generators, and the use of format test reporting schemes.

  3. 48 CFR 405.404-1 - Release procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Release procedures. 405.404-1 Section 405.404-1 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION... procedures. (a) HCA's shall establish written procedures to control the release of long-range acquisition...

  4. 19 CFR 142.48 - Release procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... manufacturer code, the quantity and unit of measure, the release site, the HTSUS number(s), the C-4 Code and... entry number, the date and time of release, the inspector's badge number, the quantity and unit of measure, and the C-4 Code will be printed on the invoice and the manifest document and, when other agency...

  5. 32 CFR 806.17 - Release and processing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Section 806.17 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.17 Release and processing procedures. (a) Individuals seeking Air Force information should address requests to an address listed in § 806.26....

  6. 32 CFR 806.17 - Release and processing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Section 806.17 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.17 Release and processing procedures. (a) Individuals seeking Air Force information should address requests to an address listed in § 806.26....

  7. 32 CFR 806.17 - Release and processing procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Section 806.17 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.17 Release and processing procedures. (a) Individuals seeking Air Force information should address requests to an address listed in § 806.26. MAJCOM...

  8. 32 CFR 806.17 - Release and processing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Section 806.17 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.17 Release and processing procedures. (a) Individuals seeking Air Force information should address requests to an address listed in § 806.26. MAJCOM...

  9. 32 CFR 806.17 - Release and processing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 806.17 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.17 Release and processing procedures. (a) Individuals seeking Air Force information should address requests to an address listed in § 806.26. MAJCOM...

  10. Photoacoustic monitoring of circulating tumor cells released during medical procedures

    NASA Astrophysics Data System (ADS)

    Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Galanzha, Ekaterina; Suen, James Y.; Zharov, Vladimir P.

    2013-03-01

    Many cancer deaths are related to metastasis to distant organs due to dissemination of circulating tumor cells (CTCs) shed from the primary tumor. For many years, oncologists believed some medical procedures may provoke metastasis; however, no direct evidence has been reported. We have developed a new, noninvasive technology called in vivo photoacoustic (PA) flow cytometry (PAFC), which provides ultrasensitive detection of CTCs. When CTCs with strongly light-absorbing intrinsic melanin pass through a laser beam aimed at a peripheral blood vessel, laser-induced acoustic waves from CTCs were detected using an ultrasound transducer. We focused on melanoma as it is one of the most metastatically aggressive malignancies. The goal of this research was to determine whether melanoma manipulation, like compression, incisional biopsy, or tumor excision, could enhance penetration of cancer cells from the primary tumor into the circulatory system. The ears of nude mice were inoculated with melanoma cells. Blood vessels were monitored for the presence of CTCs using in vivo PAFC. We discovered some medical procedures, like compression of the tumor, biopsy, and surgery may either initiate CTC release in the blood which previously contained no CTCs, or dramatically increased (10-30-fold) CTC counts above the initial level. Our results warn oncologists to use caution during physical examination, and surgery. A preventive anti-CTC therapy during or immediately after surgery, by intravenous drug administration could serve as an option to treat the resulting release of CTCs.

  11. 76 FR 19023 - Commercial Driver's License Information System State Procedures Manual, Release 5.2.0

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-06

    ... CDLIS State Procedures Manual (Release 5.2.0) outlines the standard administrative practices required of... Information System State Procedures Manual, Release 5.2.0 AGENCY: Federal Motor Carrier Safety Administration... Driver's License Information System (CDLIS) State Procedures Manual (the Manual). All State driver...

  12. 76 FR 68328 - Commercial Driver's License Information System State Procedures Manual, Release 5.2.0

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... Information System State Procedures Manual, Release 5.2.0 AGENCY: Federal Motor Carrier Safety Administration... Administrators, Inc.'s (AAMVA) Commercial Driver's License Information System (CDLIS) State Procedures Manual (the Manual) (Release 5.2.0). This final rule requires all State driver licensing agencies (SDLAs) to...

  13. Procedural Visual Learning in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Gabriel, Audrey; Stefaniak, Nicolas; Maillart, Christelle; Schmitz, Xavier; Meulemans, Thierry

    2012-01-01

    Purpose: According to the "procedural deficit hypothesis" (PDH), difficulties in the procedural learning (PL) system may contribute to the language difficulties observed in children with specific language impairment (SLI). Method: Fifteen children with SLI and their typically developing (TD) peers were compared on visual PL…

  14. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers and Tubes, Imported Into or Returned to the United States Release from Customs Custody of Tobacco Products and Cigarette Papers and...

  15. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers and Tubes, Imported Into or Returned to the United States Release from Customs Custody of Tobacco Products and Cigarette Papers and...

  16. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers and Tubes, Imported Into or Returned to the United States Release from Customs Custody of Tobacco Products and Cigarette Papers and...

  17. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Tobacco Products and Cigarette Papers and Tubes, Imported Into or Returned to the United States Release from Customs Custody of Tobacco Products and Cigarette Papers and...

  18. Aptamer-based liposomes improve specific drug loading and release.

    PubMed

    Plourde, Kevin; Derbali, Rabeb Mouna; Desrosiers, Arnaud; Dubath, Céline; Vallée-Bélisle, Alexis; Leblond, Jeanne

    2017-04-10

    Aptamer technology has shown much promise in cancer therapeutics for its targeting abilities. However, its potential to improve drug loading and release from nanocarriers has not been thoroughly explored. In this study, we employed drug-binding aptamers to actively load drugs into liposomes. We designed a series of DNA aptamer sequences specific to doxorubicin, displaying multiple binding sites and various binding affinities. The binding ability of aptamers was preserved when incorporated into cationic liposomes, binding up to 15equivalents of doxorubicin per aptamer, therefore drawing the drug into liposomes. Optimization of the charge and drug/aptamer ratios resulted in ≥80% encapsulation efficiency of doxorubicin, ten times higher than classical passively-encapsulating liposomal formulations and similar to a pH-gradient active loading strategy. In addition, kinetic release profiles and cytotoxicity assay on HeLa cells demonstrated that the release and therapeutic efficacy of liposomal doxorubicin could be controlled by the aptamer's structure. Our results suggest that the aptamer exhibiting a specific intermediate affinity is the best suited to achieve high drug loading while maintaining efficient drug release and therapeutic activity. This strategy was successfully applied to tobramycin, a hydrophilic drug suffering from low encapsulation into liposomes, where its loading was improved six-fold using aptamers. Overall, we demonstrate that aptamers could act, in addition to their targeting properties, as multifunctional excipients for liposomal formulations.

  19. Abrasion Testing of Products Containing Nanomaterials, SOP-R-2: Scientific Operating Procedure Series: Release (R)

    DTIC Science & Technology

    2016-04-01

    Scientific Operating Procedure Series: Release (R) En gi ne er R es ea rc h an d D ev el op m en t Ce nt er Monica A. Ramsey, Jonathon A. Brame...Abrasion Testing of Products Containing Nanomaterials, SOP-R-2 Scientific Operating Procedure Series: Release (R) Jonathon A. Brame, Aimee R. Poda, and...of a nanotechnology. This SOP presents a general method for abrading a material using a rotating sample platform in contact with a weighted sandpaper

  20. 31 CFR 542.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false General and specific licensing procedures. 542.501 Section 542.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SYRIAN SANCTIONS...

  1. 31 CFR 542.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false General and specific licensing procedures. 542.501 Section 542.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SYRIAN SANCTIONS...

  2. 31 CFR 542.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false General and specific licensing procedures. 542.501 Section 542.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SYRIAN SANCTIONS...

  3. 31 CFR 542.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false General and specific licensing procedures. 542.501 Section 542.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SYRIAN SANCTIONS...

  4. 31 CFR 560.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false General and specific licensing procedures. 560.501 Section 560.501 Money and Finance: Treasury Regulations Relating to Money and Finance... the Office of Foreign Assets Control's Web site (www.treasury.gov/ofac). ...

  5. 31 CFR 589.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 589.501 Section 589.501 Money and Finance: Treasury Regulations Relating to Money and Finance... page on OFAC's Web site: www.treasury.gov/ofac. ...

  6. 31 CFR 552.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 552.501 Section 552.501 Money and Finance: Treasury Regulations Relating to Money and Finance... part also may be available through the Yemen sanctions page on OFAC's Web site: www.treasury.gov/ofac. ...

  7. 31 CFR 537.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 537.501 Section 537.501 Money and Finance: Treasury Regulations Relating to Money and Finance... site: www.treasury.gov/ofac. ...

  8. 31 CFR 590.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false General and specific licensing procedures. 590.501 Section 590.501 Money and Finance: Treasury Regulations Relating to Money and Finance...'s Web site: http://www.treasury.gov/resource-center/sanctions/programs/pages/tco.aspx. ...

  9. 31 CFR 570.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 570.501 Section 570.501 Money and Finance: Treasury Regulations Relating to Money and Finance... Web site: http://www.treasury.gov/resource-center/sanctions/programs/pages/libya.aspx. ...

  10. 31 CFR 560.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 560.501 Section 560.501 Money and Finance: Treasury Regulations Relating to Money and Finance... the Office of Foreign Assets Control's Web site (www.treasury.gov/ofac). ...

  11. 31 CFR 552.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false General and specific licensing procedures. 552.501 Section 552.501 Money and Finance: Treasury Regulations Relating to Money and Finance... part also may be available through the Yemen sanctions page on OFAC's Web site: www.treasury.gov/ofac. ...

  12. 31 CFR 590.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 590.501 Section 590.501 Money and Finance: Treasury Regulations Relating to Money and Finance...'s Web site: http://www.treasury.gov/resource-center/sanctions/programs/pages/tco.aspx. ...

  13. 31 CFR 558.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 558.501 Section 558.501 Money and Finance: Treasury Regulations Relating to Money and Finance...'s Web site: www.treasury.gov/ofac. ...

  14. 31 CFR 542.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 542.501 Section 542.501 Money and Finance: Treasury Regulations Relating to Money and Finance... site www.treasury.gov/ofac. ...

  15. 31 CFR 570.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false General and specific licensing procedures. 570.501 Section 570.501 Money and Finance: Treasury Regulations Relating to Money and Finance... Web site: http://www.treasury.gov/resource-center/sanctions/programs/pages/libya.aspx. ...

  16. 31 CFR 548.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false General and specific licensing procedures. 548.501 Section 548.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS...

  17. 31 CFR 548.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false General and specific licensing procedures. 548.501 Section 548.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS...

  18. 31 CFR 548.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false General and specific licensing procedures. 548.501 Section 548.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS...

  19. 31 CFR 548.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false General and specific licensing procedures. 548.501 Section 548.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS...

  20. 31 CFR 548.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 548.501 Section 548.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS...

  1. 31 CFR 586.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false General and specific licensing procedures. 586.501 Section 586.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FEDERAL REPUBLIC OF...

  2. 31 CFR 549.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false General and specific licensing procedures. 549.501 Section 549.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY LEBANON SANCTIONS REGULATIONS...

  3. 31 CFR 543.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false General and specific licensing procedures. 543.501 Section 543.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY CôTE D'IVOIRE SANCTIONS...

  4. 31 CFR 510.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false General and specific licensing procedures. 510.501 Section 510.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS...

  5. 31 CFR 510.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false General and specific licensing procedures. 510.501 Section 510.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS...

  6. 31 CFR 510.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false General and specific licensing procedures. 510.501 Section 510.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS...

  7. 31 CFR 510.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false General and specific licensing procedures. 510.501 Section 510.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS...

  8. 31 CFR 547.501 - General and specific licensing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false General and specific licensing procedures. 547.501 Section 547.501 Money and Finance: Treasury Regulations Relating to Money and Finance... SANCTIONS REGULATIONS Licenses, Authorizations, and Statements of Licensing Policy § 547.501 General and...

  9. Working, declarative and procedural memory in specific language impairment

    PubMed Central

    Lum, Jarrad A.G.; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T.

    2012-01-01

    According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact, and should play an important compensatory role for grammar. These claims were tested by examining measures of working, declarative and procedural memory in 51 children with SLI and 51 matched typically-developing (TD) children (mean age 10). Working memory was assessed with the Working Memory Test Battery for Children, declarative memory with the Children’s Memory Scale, and procedural memory with a visuo-spatial Serial Reaction Time task. As compared to the TD children, the children with SLI were impaired at procedural memory, even when holding working memory constant. In contrast, they were spared at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed neither visuo-spatial nor verbal working memory was associated with either lexical or grammatical abilities in either the SLI or TD children. Declarative memory correlated with lexical abilities in both groups of children. Finally, grammatical abilities were associated with procedural memory in the TD children, but with declarative memory in the children with SLI. These findings replicate and extend previous studies of working, declarative and procedural memory in SLI. Overall, we

  10. Working, declarative and procedural memory in specific language impairment.

    PubMed

    Lum, Jarrad A G; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T

    2012-10-01

    According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact, and should play an important compensatory role for grammar. These claims were tested by examining measures of working, declarative and procedural memory in 51 children with SLI and 51 matched typically-developing (TD) children (mean age 10). Working memory was assessed with the Working Memory Test Battery for Children, declarative memory with the Children's Memory Scale, and procedural memory with a visuo-spatial Serial Reaction Time task. As compared to the TD children, the children with SLI were impaired at procedural memory, even when holding working memory constant. In contrast, they were spared at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed neither visuo-spatial nor verbal working memory was associated with either lexical or grammatical abilities in either the SLI or TD children. Declarative memory correlated with lexical abilities in both groups of children. Finally, grammatical abilities were associated with procedural memory in the TD children, but with declarative memory in the children with SLI. These findings replicate and extend previous studies of working, declarative and procedural memory in SLI. Overall, we

  11. Combinatorial screening for specific drug solubilizers with switchable release profiles.

    PubMed

    Wieczorek, Sebastian; Vigne, Sara; Masini, Tiziana; Ponader, Daniela; Hartmann, Laura; Hirsch, Anna K H; Börner, Hans G

    2015-01-01

    Polymer-block-peptide conjugates are tailored to render hydrophobic small molecule drugs water soluble. The combinatorial strategy selects for bioconjugates that exhibit sequence-specific solubilization and switchable release profiles of the cargo through incorporation of a disulfide linker moiety into the peptide-library design. While the study focused on the photosensitizer m-THPC and reductive carrier cleavage, the approach is generic and might be expanded toward a broad range of poorly soluble small-molecule drugs and other selective cleavage mechanisms to disassemble a peptide binding domain of the bioconjugate-based solubilizer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. An iterative requirements specification procedure for decision support systems.

    PubMed

    Brookes, C H

    1987-08-01

    Requirements specification is a key element in a DSS development project because it not only determines what is to be done, it also drives the evolution process. A procedure for requirements elicitation is described that is based on the decomposition of the DSS design task into a number of functions, subfunctions, and operators. It is postulated that the procedure facilitates the building of a DSS that is complete and integrates MIS, modelling and expert system components. Some examples given are drawn from the health administration field.

  13. Sequence-Specific Procedural Learning Deficits in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Hsu, Hsinjen Julie; Bishop, Dorothy V. M.

    2014-01-01

    This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children's performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n = 48), typically developing age-matched children (n = 20) and younger…

  14. NIF Anti-Reflective Coating Solutions: Preparation, Procedures and Specifications

    SciTech Connect

    Suratwala, T; Carman, L; Thomas, I

    2003-07-01

    The following document contains a detailed description of the preparation procedures for the antireflective coating solutions used for NIF optics. This memo includes preparation procedures for the coating solutions (sections 2.0-4.0), specifications and vendor information of the raw materials used and on all equipment used (section 5.0), and QA specifications (section 6.0) and procedures (section 7.0) to determine quality and repeatability of all the coating solutions. There are different five coating solutions that will be used to coat NIF optics. These solutions are listed below: (1) Colloidal silica (3%) in ethanol (2) Colloidal silica (2%) in sec-butanol (3) Colloidal silica (9%) in sec-butanol (deammoniated) (4) HMDS treated silica (10%) in decane (5) GR650 (3.3%) in ethanol/sec-butanol The names listed above are to be considered the official name for the solution. They will be referred to by these names in the remainder of this document. Table 1 gives a summary of all the optics to be coated including: (1) the surface to be coated; (2) the type of solution to be used; (3) the coating method (meniscus, dip, or spin coating) to be used; (4) the type of coating (broadband, 1?, 2?, 3?) to be made; (5) number of optics to be coated; and (6) the type of post processing required (if any). Table 2 gives a summary of the batch compositions and measured properties of all five of these solutions.

  15. Procedural visual learning in children with specific language impairment.

    PubMed

    Gabriel, Audrey; Stefaniak, Nicolas; Maillart, Christelle; Schmitz, Xavier; Meulemans, Thierry

    2012-11-01

    According to the procedural deficit hypothesis (PDH), difficulties in the procedural learning (PL) system may contribute to the language difficulties observed in children with specific language impairment (SLI). Fifteen children with SLI and their typically developing (TD) peers were compared on visual PL tasks-specifically, deterministic serial reaction time (SRT) tasks. In the first experiment, children with SLI and their TD peers performed the classical SRT task using a keyboard as response mode. In the second experiment, they performed the same SRT task but gave their responses through a touchscreen (instead of a keyboard) to reduce the motor and cognitive demands of the task. Although in Experiment 1, children with SLI demonstrated learning, they were slower and made more errors than did their TD peers. Nevertheless, these relative weaknesses disappeared when the nature of the response mode changed ( Experiment 2). In this study, the authors report that children with SLI may exhibit sequential learning. Moreover, the generally slower reaction times observed in previous deterministic SRT studies may be explained by the response mode used. Thus, our findings are not consistent with the predictions of the PDH, and these findings suggest that language impairments in SLI are not sustained by poor procedural learning abilities.

  16. Percutaneous Ultrasonic Fasciotomy for Refractory Plantar Fasciopathy After Failure of a Partial Endoscopic Release Procedure.

    PubMed

    Pourcho, Adam M; Hall, Mederic M

    2015-11-01

    Plantar fasciopathy is a painful, degenerative condition of the plantar fascia that affects 2 million people annually and has an estimated 10% lifetime prevalence. When both nonoperative and operative management fails, patients have limited therapeutic options. We present a case of an active 47-year-old male runner who was successfully treated with songraphically guided percutaneous ultrasonic fasciotomy after undergoing a prolonged course of nonoperative management and an endoscopic plantar fascia release procedure. Percutaneous ultrasonic fasciotomy may be considered in patients with chronic, refractory plantar fasciopathy, including those for whom a prior operative release procedure has failed.

  17. Isomer-Specific Analysis of Released N-Glycans by LC-ESI MS/MS with Porous Graphitized Carbon.

    PubMed

    Kolarich, Daniel; Windwarder, Markus; Alagesan, Kathirvel; Altmann, Friedrich

    2015-01-01

    The combination of porous graphitized carbon (PGC) liquid chromatography (LC) with mass spectrometric (MS) detection probably constitutes the most elaborate single stage analysis for isomer-specific N-glycan analysis. Here, we describe sample preparation and analysis procedures for the identification of released N-glycans using PGC-LC-ESI-MS and MS/MS.

  18. Benchmarking Procedures for High-Throughput Context Specific Reconstruction Algorithms

    PubMed Central

    Pacheco, Maria P.; Pfau, Thomas; Sauter, Thomas

    2016-01-01

    Recent progress in high-throughput data acquisition has shifted the focus from data generation to processing and understanding of how to integrate collected information. Context specific reconstruction based on generic genome scale models like ReconX or HMR has the potential to become a diagnostic and treatment tool tailored to the analysis of specific individuals. The respective computational algorithms require a high level of predictive power, robustness and sensitivity. Although multiple context specific reconstruction algorithms were published in the last 10 years, only a fraction of them is suitable for model building based on human high-throughput data. Beside other reasons, this might be due to problems arising from the limitation to only one metabolic target function or arbitrary thresholding. This review describes and analyses common validation methods used for testing model building algorithms. Two major methods can be distinguished: consistency testing and comparison based testing. The first is concerned with robustness against noise, e.g., missing data due to the impossibility to distinguish between the signal and the background of non-specific binding of probes in a microarray experiment, and whether distinct sets of input expressed genes corresponding to i.e., different tissues yield distinct models. The latter covers methods comparing sets of functionalities, comparison with existing networks or additional databases. We test those methods on several available algorithms and deduce properties of these algorithms that can be compared with future developments. The set of tests performed, can therefore serve as a benchmarking procedure for future algorithms. PMID:26834640

  19. A Ca2+-activated ATPase specifically released by Ca2+ shock from Paramecium tetraurelia.

    PubMed

    Riddle, L M; Rauh, J J; Nelson, D L

    1982-06-14

    Deciliation of Paramecium tetraurelia by a Ca2+ shock procedure releases a discrete set of proteins which represent about 1% of the total cell protein. Marker enzymes for cytoplasm (hexokinase), endoplasmic reticulum (glucose-6-phosphatase), peroxisomes (catalase), and lysosomes (acid phosphatase) were not released by this treatment. Among the proteins selectively released is a Ca2+-dependent ATPase. This enzyme has a broad substrate specificity which includes GTP, ATP, and UTP, and it can be activated by Ca2+, Sr2+, or Ba2+, but not by Mg2+ or by monovalent cations. The crude enzyme has a specific activity of 2-3 mumol/min per mg; the optimal pH for activity is 7.5. ATPase, GTPase, and UTPase all reside in the same protein, which is inhibited by ruthenium red, is irreversibly denatured at 50 degrees C, and which has a sedimentation coefficient of 8-10 S. This enzyme is compared with other surface-derived ATPases of ciliated protozoans, and its possible roles are discussed.

  20. Endovascular repair of abdominal aortic aneurysms: vascular anatomy, device selection, procedure, and procedure-specific complications.

    PubMed

    Bryce, Yolanda; Rogoff, Philip; Romanelli, Donald; Reichle, Ralph

    2015-01-01

    Abdominal aortic aneurysm (AAA) is abnormal dilatation of the aorta, carrying a substantial risk of rupture and thereby marked risk of death. Open repair of AAA involves lengthy surgery time, anesthesia, and substantial recovery time. Endovascular aneurysm repair (EVAR) provides a safer option for patients with advanced age and pulmonary, cardiac, and renal dysfunction. Successful endovascular repair of AAA depends on correct selection of patients (on the basis of their vascular anatomy), choice of the correct endoprosthesis, and familiarity with the technique and procedure-specific complications. The type of aneurysm is defined by its location with respect to the renal arteries, whether it is a true or false aneurysm, and whether the common iliac arteries are involved. Vascular anatomy can be divided more technically into aortic neck, aortic aneurysm, pelvic perfusion, and iliac morphology, with grades of difficulty with respect to EVAR, aortic neck morphology being the most common factor to affect EVAR appropriateness. When choosing among the devices available on the market, one must consider the patient's vascular anatomy and choose between devices that provide suprarenal fixation versus those that provide infrarenal fixation. A successful technique can be divided into preprocedural imaging, ancillary procedures before AAA stent-graft placement, the procedure itself, postprocedural medical therapy, and postprocedural imaging surveillance. Imaging surveillance is important in assessing complications such as limb thrombosis, endoleaks, graft migration, enlargement of the aneurysm sac, and rupture. Last, one must consider the issue of radiation safety with regard to EVAR.

  1. EPICS release 3.11 specific documentation -- EPICS release notes for 3.11

    SciTech Connect

    1994-01-19

    EPICS release 3.11 is now ready for user testing. A person who wants to set up a simplified application environment to boot an IOC and create databases using R3.11 should follow the directions in Appendix B, page 27, of the EPICS Source/Release Control Manual, Sept. 20, 1993. The R3.11 EPICS path at ANL/APS is /net/phebos/epics/R3.11 so the command to get the new release is /net/phebos/epics/R3.11/Unix/share/bin/getrel /net/phebos/epics/R3.11. An existing R3.8 short form report can be copied to this new directory and used to create a database. ANL/APS is currently testing an Application Developers Source/Release control system. It is not yet ready for general distribution. Attached are the EPICS R3.11 release notes.

  2. Sequence-specific procedural learning deficits in children with specific language impairment.

    PubMed

    Hsu, Hsinjen Julie; Bishop, Dorothy V M

    2014-05-01

    This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children's performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n = 48), typically developing age-matched children (n = 20) and younger typically developing children matched for receptive grammar (n = 28). In a serial reaction time task, the children with SLI performed at the same level as the grammar-matched children, but poorer than age-matched controls in learning motor sequences. When tested with a motor procedural learning task that did not involve learning sequential relationships between discrete elements (i.e. pursuit rotor), the children with SLI performed comparably with age-matched children and better than younger grammar-matched controls. In addition, poor implicit learning of word sequences in a verbal memory task (the Hebb effect) was found in the children with SLI. Together, these findings suggest that SLI might be characterized by deficits in learning sequence-specific information, rather than generally weak procedural learning. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

  3. Sequence-specific procedural learning deficits in children with specific language impairment

    PubMed Central

    Hsu, Hsinjen Julie; Bishop, Dorothy VM

    2014-01-01

    This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children’s performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n = 48), typically developing age-matched children (n = 20) and younger typically developing children matched for receptive grammar (n = 28). In a serial reaction time task, the children with SLI performed at the same level as the grammar-matched children, but poorer than age-matched controls in learning motor sequences. When tested with a motor procedural learning task that did not involve learning sequential relationships between discrete elements (i.e. pursuit rotor), the children with SLI performed comparably with age-matched children and better than younger grammar-matched controls. In addition, poor implicit learning of word sequences in a verbal memory task (the Hebb effect) was found in the children with SLI. Together, these findings suggest that SLI might be characterized by deficits in learning sequence-specific information, rather than generally weak procedural learning. PMID:24410990

  4. A systematic review on diagnostic procedures for specific language impairment: The sensitivity and specificity issues.

    PubMed

    Shahmahmood, Toktam Maleki; Jalaie, Shohreh; Soleymani, Zahra; Haresabadi, Fatemeh; Nemati, Parvin

    2016-01-01

    Identification of children with specific language impairment (SLI) has been viewed as both necessity and challenge. Investigators and clinicians use different tests and measures for this purpose. Some of these tests/measures have good psychometric properties, but it is not sufficient for diagnostic purposes. A diagnostic procedure can be used for identification a specific population with confidence only when its sensitivity and specificity are acceptable. In this study, we searched for tests/measures with predefined sensitivity and specificity for identification of preschool children with SLI from their typically developing peers. A computerized search in bibliographic databases from 2000 to August 2015 was performed with the following keywords: "specific language impairment" or SLI" and "primary language impairment" or 'PLI' with at least one of the followings: "diagnosis," "identification," "accuracy," "sensitivity," and "specificity." In addition, the related citations and reference lists of the selected articles were considered. The results of reviewing 23 included studies show that the index measures used in studies vary in accuracy with the sensitivity ranging from 16% to 100% and the specificity ranging from 14% to 100%. These varieties in sensitivity and specificity of different tests/measures confirm the necessity of attention to the diagnostic power of tests/measures before their use as diagnostic tool. Further, the results indicate there are some promising tests/measures that the available evidence supports their performances in the diagnosis of SLI in preschool-aged children, yet the place of a reference standard for the diagnosis of SLI is vacant among investigations.

  5. A systematic review on diagnostic procedures for specific language impairment: The sensitivity and specificity issues

    PubMed Central

    Shahmahmood, Toktam Maleki; Jalaie, Shohreh; Soleymani, Zahra; Haresabadi, Fatemeh; Nemati, Parvin

    2016-01-01

    Background: Identification of children with specific language impairment (SLI) has been viewed as both necessity and challenge. Investigators and clinicians use different tests and measures for this purpose. Some of these tests/measures have good psychometric properties, but it is not sufficient for diagnostic purposes. A diagnostic procedure can be used for identification a specific population with confidence only when its sensitivity and specificity are acceptable. In this study, we searched for tests/measures with predefined sensitivity and specificity for identification of preschool children with SLI from their typically developing peers. Materials and Methods: A computerized search in bibliographic databases from 2000 to August 2015 was performed with the following keywords: “specific language impairment” or SLI” and “primary language impairment” or ‘PLI’ with at least one of the followings: “diagnosis,” “identification,” “accuracy,” “sensitivity,” and “specificity.” In addition, the related citations and reference lists of the selected articles were considered. Results: The results of reviewing 23 included studies show that the index measures used in studies vary in accuracy with the sensitivity ranging from 16% to 100% and the specificity ranging from 14% to 100%. Conclusion: These varieties in sensitivity and specificity of different tests/measures confirm the necessity of attention to the diagnostic power of tests/measures before their use as diagnostic tool. Further, the results indicate there are some promising tests/measures that the available evidence supports their performances in the diagnosis of SLI in preschool-aged children, yet the place of a reference standard for the diagnosis of SLI is vacant among investigations. PMID:27904612

  6. EPICS release 3.11.6 specific documentation -- Release notes for EPICS 3.11.6

    SciTech Connect

    1994-06-07

    These notes cover the following: (1) directions for switching to production APS release R3.11.6; (2) unbundling of channel access clients; (3) access security; (4) channel access additions; synchronous time support; and (5) description of major differences between R3.11.3 and R3.11.6 Also included is a list of new and/or updated documentation for the program.

  7. 10 CFR 32.110 - Acceptance sampling procedures under certain specific licenses.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL Quality Control Sampling Procedures § 32.110 Acceptance sampling procedures under certain specific licenses. (a) A random sample shall be taken... 10 Energy 1 2012-01-01 2012-01-01 false Acceptance sampling procedures under certain specific...

  8. Stabilization of spontaneous neurotransmitter release at ribbon synapses by ribbon-specific subtypes of Complexin

    PubMed Central

    Vaithianathan, Thirumalini; Zanazzi, George; Henry, Diane; Akmentin, Wendy; Matthews, Gary

    2013-01-01

    Ribbon synapses of tonically releasing sensory neurons must provide a large pool of releasable vesicles for sustained release, while minimizing spontaneous release in the absence of stimulation. Complexins are presynaptic proteins that may accomplish this dual task at conventional synapses, by interacting with the molecular machinery of synaptic vesicle fusion at the active zone to retard spontaneous vesicle exocytosis yet facilitate release evoked by depolarization. However, ribbon synapses of photoreceptor cells and bipolar neurons in the retina express distinct Complexin subtypes, perhaps reflecting the special requirements of these synapses for tonic release. To investigate the role of ribbon-specific Complexins in transmitter release, we combined presynaptic voltage-clamp, fluorescence imaging, electron microscopy, and behavioral assays of photoreceptive function in zebrafish. Acute interference with Complexin function using a peptide derived from the SNARE-binding domain increased spontaneous synaptic vesicle fusion at ribbon synapses of retinal bipolar neurons without affecting release triggered by depolarization. Knockdown of Complexin by injection of an antisense morpholino into zebrafish embryos prevented photoreceptor-driven migration of pigment in skin melanophores and caused the pigment distribution to remain in the dark-adapted state even when embryos were exposed to light. This suggests that loss of Complexin function elevated spontaneous release in illuminated photoreceptors sufficiently to mimic the higher release rate normally associated with darkness, thus interfering with visual signaling. We conclude that visual system-specific Complexins are required for proper illumination-dependent modulation of the rate of neurotransmitter release at visual system ribbon synapses. PMID:23658160

  9. Stabilization of spontaneous neurotransmitter release at ribbon synapses by ribbon-specific subtypes of complexin.

    PubMed

    Vaithianathan, Thirumalini; Zanazzi, George; Henry, Diane; Akmentin, Wendy; Matthews, Gary

    2013-05-08

    Ribbon synapses of tonically releasing sensory neurons must provide a large pool of releasable vesicles for sustained release, while minimizing spontaneous release in the absence of stimulation. Complexins are presynaptic proteins that may accomplish this dual task at conventional synapses by interacting with the molecular machinery of synaptic vesicle fusion at the active zone to retard spontaneous vesicle exocytosis yet facilitate release evoked by depolarization. However, ribbon synapses of photoreceptor cells and bipolar neurons in the retina express distinct complexin subtypes, perhaps reflecting the special requirements of these synapses for tonic release. To investigate the role of ribbon-specific complexins in transmitter release, we combined presynaptic voltage clamp, fluorescence imaging, electron microscopy, and behavioral assays of photoreceptive function in zebrafish. Acute interference with complexin function using a peptide derived from the SNARE-binding domain increased spontaneous synaptic vesicle fusion at ribbon synapses of retinal bipolar neurons without affecting release triggered by depolarization. Knockdown of complexin by injection of an antisense morpholino into zebrafish embryos prevented photoreceptor-driven migration of pigment in skin melanophores and caused the pigment distribution to remain in the dark-adapted state even when embryos were exposed to light. This suggests that loss of complexin function elevated spontaneous release in illuminated photoreceptors sufficiently to mimic the higher release rate normally associated with darkness, thus interfering with visual signaling. We conclude that visual system-specific complexins are required for proper illumination-dependent modulation of the rate of neurotransmitter release at visual system ribbon synapses.

  10. Procedure for detecting underground utilities with specific shape

    NASA Astrophysics Data System (ADS)

    Ristic, Aleksandar; Vrtunski, Milan; Govedarica, Miro; Bugarinovic, Zeljko

    2016-04-01

    Nowadays GPR technology is acknowledged as a reliable, fast, non-destructive remote sensing technology whose area of applications is wider every day. One of its most common applications is underground utility detection. Not only it is possible to detect the utility in the field, but using certain algorithms utilities which haven't been detected in the field can be detected in radargrams. There is a number of procedures for automated detection of utility in the radargrams. Further, there are procedures that can estimate certain parameters such as propagation velocity, diameter or even characteristics of the material. However, the majority of these procedures is designed to detect cylindrical shape utilities, which, in a radargram, are represented with hyperbolic reflection. According to geometry of hyperbola, utility parameters can be estimated. In this paper we present a procedure that is designed to estimate characteristics of non-cylindrical utilities. It is worth mentioning that these utilities are not so rare. Some underground tanks and sewage collectors are among them. Heat line is consisted of two insulated pipes of the same diameter, often placed in a concrete channel and covered with plates made from reinforced concrete. Therefore, it can be considered as non-cylindrical utility and such structure has characteristic signature in a radargram. The main idea of the proposed procedure is to detect this signature, and then, based on standardized parameters for the heat lines, to estimate the diameter of the pipes. The proposed procedure is based on artificial neural network. As a training set we made a number of radargrams collected on different locations which contain heat lines of various dimensions. Pipe diameters were in a range from 65 to 250 mm. 400MHz antenna was used since the depth hasn't exceeded 2m. After the network is trained it is validated using radargrams that haven't been used in the training set. Further tests were done with radargrams that

  11. High Voltage Testing. Volume 2. Specifications and Test Procedures

    DTIC Science & Technology

    1982-08-01

    as tested to 4.7.12 shall exhibit no evidence of mechanical damage. 103 °o. . .. 3.16 Salt spray (corrosion) (metal surfaces only, see 3.1). When...of the surfaces shall be affected by flaking, peeling, or blistering of paint. There shall be no evidence of unwrapping of or mechanical damage to...Profile 48 A6 Typical Mechanical Release Fixture 50 A7 Suggested Method for Making Cable Ends Corona Free 56 BI Solder Contact (Pin and Socket

  12. Site-Specific, Sustained Release of Drugs to the Brain

    NASA Astrophysics Data System (ADS)

    Bodor, Nicholas; Farag, Hassan H.; Brewster, Marcus E.

    1981-12-01

    A dihydropyridine-pyridinium salt type of redox system is used in a general and flexible method for site-specific or sustained delivery (or both) of drugs to the brain. A biologically active compound linked to a lipoidal dihydropyridine carrier easily penetrates the blood-brain barrier. Oxidation of the carrier part in vivo to the ionic pyridinium salt prevents its elimination from the brain, while elimination from the general circulation is accelerated. Subsequent cleavage of the quaternary carrier-drug species results in sustained delivery of the drug in the brain and facile elimination of the carrier part.

  13. Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Verissimo, Joao; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have…

  14. Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Verissimo, Joao; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have…

  15. Fluorescence nanoscopy of platelets resolves platelet-state specific storage, release and uptake of proteins, opening up future diagnostic applications.

    PubMed

    Rönnlund, Daniel; Yang, Yang; Blom, Hans; Auer, Gert; Widengren, Jerker

    2012-11-01

    Dysregulation of how platelets store, sequester and release specific proteins seems to be implicated in many disease states, including cancer. Dual-color immunofluorescence stimulated emission depletion (STED) microscopy with 40 nm resolution is used to map pro-angiogenic VEGF, anti-angiogenic PF-4 and fibrinogen in >300 individual platelets. This reveals that these proteins are stored in a segmented, zonal manner within regional clusters, significantly smaller than the size of an α-granule. No colocalization between the different proteins is observed. Upon platelet activation by thrombin or ADP, the proteins undergo significant spatial rearrangements, including alterations in the size and number of the protein clusters, and specific for a certain protein and the type of activation induced. Following these observations, a simple assignment procedure is used to show that the three distinct states of platelets (non-, ADP- and thrombin-activated) can be identified based on the average size, number and peripheral localization profiles of the regional protein clusters within the platelets. Thus, high-resolution spatial mapping of specific proteins is a useful procedure to detect and characterize deviations in the selective storage, release and uptake of these proteins in the platelets. Since these deviations seem to be specific for, and may even underlie, certain patophysiological states, these findings may have interesting diagnostic and therapeutic implications.

  16. 33 CFR 157.420 - Vessel specific watch policy and procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Vessel specific watch policy and procedures. 157.420 Section 157.420 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... § 157.420 Vessel specific watch policy and procedures. (a) Not later than February 1, 1997, the owner...

  17. 10 CFR 32.110 - Acceptance sampling procedures under certain specific licenses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Acceptance sampling procedures under certain specific licenses. 32.110 Section 32.110 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL Quality Control Sampling Procedures § 32...

  18. 40 CFR Appendix A to Part 75 - Specifications and Test Procedures

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Specifications and Test Procedures A Appendix A to Part 75 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Pt. 75, App. A Appendix A to Part 75—Specifications and Test Procedures 1. Installation and Measuremen...

  19. Development of electrical test procedures for qualification of spacecraft against EID. Volume 2: Review and specification of test procedures

    NASA Technical Reports Server (NTRS)

    Wilkenfeld, J. M.; Harlacher, B. L.; Mathews, D.

    1982-01-01

    A combined experimental and analytical program to develop system electrical test procedures for the qualification of spacecraft against damage produced by space-electron-induced discharges (EID) occurring on spacecraft dielectric outer surfaces is described. A review and critical evaluation of possible approaches to qualify spacecraft against space electron-induced discharges (EID) is presented. A variety of possible schemes to simulate EID electromagnetic effects produced in spacecraft was studied. These techniques form the principal element of a provisional, recommended set of test procedures for the EID qualification spacecraft. Significant gaps in our knowledge about EID which impact the final specification of an electrical test to qualify spacecraft against EID are also identified.

  20. Using Decision Procedures to Build Domain-Specific Deductive Synthesis Systems

    NASA Technical Reports Server (NTRS)

    VanBaalen, Jeffrey; Roach, Steven; Lau, Sonie (Technical Monitor)

    1998-01-01

    This paper describes a class of decision procedures that we have found useful for efficient, domain-specific deductive synthesis. These procedures are called closure-based ground literal satisfiability procedures. We argue that this is a large and interesting class of procedures and show how to interface these procedures to a theorem prover for efficient deductive synthesis. Finally, we describe some results we have observed from our implementation. Amphion/NAIF is a domain-specific, high-assurance software synthesis system. It takes an abstract specification of a problem in solar system mechanics, such as 'when will a signal sent from the Cassini spacecraft to Earth be blocked by the planet Saturn?', and automatically synthesizes a FORTRAN program to solve it.

  1. 17 CFR 201.202 - Specification of procedures by parties in certain proceedings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... § 201.202 Specification of procedures by parties in certain proceedings. (a) Motion to specify... the start of a hearing, make a motion to specify the procedures necessary or appropriate for the... Commission's order and the date it is to become effective. (b) Objections; effect of failure to object. Any...

  2. 17 CFR 201.202 - Specification of procedures by parties in certain proceedings.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... § 201.202 Specification of procedures by parties in certain proceedings. (a) Motion to specify... the start of a hearing, make a motion to specify the procedures necessary or appropriate for the... Commission's order and the date it is to become effective. (b) Objections; effect of failure to object. Any...

  3. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... requirements under HUD building products certification program for solid fuel type room heaters and fireplace... Supplementary specific procedural requirements under HUD building products certification program for solid fuel... fireplace stoves certified under the HUD Building Products Certification Program shall be...

  4. Improving consent form documentation and introduction of procedure-specific labels in a district general hospital

    PubMed Central

    Bajada, Stefan; Dwamena, Samuel; Abdul, Zabihullah; Williams, Rhodri; Ennis, Owain

    2017-01-01

    Informed consent is an important aspect in patient care. Failings in this area may result in patient dissatisfaction or litigation. The aim of this project was to assess our practice in consenting and institute changes to maintain best practice. A consecutive series of 140 patients undergoing elective and trauma procedures were randomly identified over a nine-month period. The consent forms were reviewed and the following information collected: patient/ consenter details, procedure, legibility, if copy was offered/ given to patient and adequacy of procedure-specific complications listed (scored 0-3). The issues identified included: 25% of consents were not fully legible particularly in the complications section. 62% were noted to have inadequate complications listed (score 0 [>5 risks missing]) when compared to an accepted standard. None of the consent form copies were offered or given to the patients. Focused teaching to juniors as well as procedure-specific complication stickers were implemented to improve the documentation of complications. Following several improvement cycles all consents (100%) were fully legible and had the adequate procedure-specific labels with all complications listed. There was an increase to 38% of consent forms offered to patients. We have asked surgeons in the department to comment on which consent method they prefer and all consenters felt that the procedure-specific labels where easier to read and understand. Departmental education as well as introduction of simple procedure-specific complication stickers has resulted in significant improvements in practice. PMID:28243444

  5. Substrate specificity of the agonist-stimulated release of polyunsaturated fatty acids from vascular endothelial cells

    SciTech Connect

    Rosenthal, M.D.; Garcia, M.C.; Sprecher, H. )

    1989-11-01

    Stimulation of vascular endothelial cells with agonists such as histamine and thrombin results in release of arachidonic acid from membrane lipids and subsequent eicosanoid synthesis. As shown previously, the agonist-stimulated deacylation is specific for arachidonate, eicosapentaenoate, and 5,8,11-eicosatrienoate. This study has utilized radiolabeled fatty acids differing in chain length and position of double bonds to further elucidate the fatty acyl specificity of agonist-stimulated deacylation. Replicate wells of confluent human umbilical vein endothelial cells were incubated with 14C-labeled fatty acids and then challenged with histamine, thrombin, or the calcium ionophore A23187. Comparison of the results obtained with isomeric eicosatetraenoic fatty acids with initial double bonds at carbons 4, 5, or 6 indicated that the deacylation induced by all three agonists exhibited marked specificity for the cis-5 double bond. Lack of stringent chain length specificity was indicated by agonist-stimulated release of 5,8,11,14- tetraenoic fatty acids with 18, 19, 20, and 21 carbons. Release of 5,8,14-(14C)eicosatrienoate was two-to threefold that of 5,11,14-(14C)eicosatrienoate, thus indicating that the cis-8 double bond may also contribute to the stringent recognition by the agonist-sensitive phospholipase. The present study has also demonstrated that histamine, thrombin, and A23187 do not stimulate release of docosahexaenoate from endothelial cells.

  6. A modified release analysis procedure using advanced froth flotation mechanisms. Final technical report, September 1, 1995--August 31, 1996

    SciTech Connect

    Honaker, R.Q.; Mohanty, M.K.

    1997-05-01

    Recent studies indicate that the optimum separation performances achieved by multiple stage cleaning using various column flotation technologies and single stage cleaning using a Packed-Flotation Column are superior to the performance achieved by the traditional release procedure, especially in terms of pyritic sulfur rejection. This superior performance is believed to be the result of the advanced flotation mechanisms provided by column flotation technologies. Thus, the objective of this study was to develop a suitable process utilizing the advanced froth flotation mechanisms to characterize the true flotation response of a coal sample. This investigation resulted in the development of a modified coal flotation characterization procedure, termed as the Advanced Flotation Washability (AFW) technique. The apparatus used for this procedure is a batch operated Packed-Column device which provides enhanced selectivity due to a plug-flow environment and a deep froth zone. The separation performance achieved by the AFW procedure was found to be superior to those produced by the conventional tree and release procedures for three nominally -100 mesh coal samples and two micronized samples. The largest difference in separation performance was obtained on the basis of product pyritic sulfur content. A comparison conducted between the AFW and the release procedures at an 80% recovery value showed that the AFW technique provided a 19% improvement in the reduction of pyritic sulfur. For an Illinois No. 5 coal sample, this improvement corresponded to a reduction in pyritic sulfur content from 1.38% to 0.70% or a total rejection of 66%. Micronization of the sample improved the pyritic sulfur rejection to 85% while rejecting 92% of the ash-bearing material. In addition, the separation performance provided by the AFW procedure was superior to that obtained from multiple cleaning stages using a continuous Packed-Column under both kinetic and carrying-capacity limiting conditions.

  7. Development of Floating-Mucoadhesive Microsphere for Site Specific Release of Metronidazole

    PubMed Central

    Amin, Md. Lutful; Ahmed, Tajnin; Mannan, Md. Abdul

    2016-01-01

    Purpose: The purpose of this study was to develop and evaluate metronidazole loaded floating-mucoadhesive microsphere for sustained drug release at the gastric mucosa. Methods: Alginate gastroretentive microspheres containing metronidazole were prepared by ionic gelation method using sodium bicarbonate as gas forming agent, guar gum as mucoadhesive polymer, and Eudragit L100 as drug release modifier. Carbopol was used for increasing the bead strength. The microspheres were characterized by scanning electron microscopy and evaluated by means of drug entrapment efficiency, in vitro buoyancy, and swelling studies. In vitro mucoadhesion and drug release studies were carried out in order to evaluate site specific sustained drug release. Results: All formulations showed 100% buoyancy in vitro for a prolonged period of time. Amount of guar gum influenced the properties of different formulations. The formulation containing drug and guar gum at a ratio of 1:0.5 showed the best results with 76.3% drug entrapment efficiency, 61.21% mucoadhesion, and sustained drug release. Carbopol was found to increase surface smoothness of the microspheres. Conclusion: Metronidazole mucoadhesive-floating microspheres can be effectively used for sustained drug release to the gastric mucosa in treatment of upper GIT infection. PMID:27478781

  8. Quantifying Nanoparticle Release from Nanotechnology: Scientific Operating Procedure Series: SOP C 3

    DTIC Science & Technology

    2017-02-01

    Approved for public release; distribution is unlimited. The U.S. Army Engineer Research and Development Center (ERDC) solves the nation’s toughest...engineering and environmental challenges. ERDC develops innovative solutions in civil and military engineering, geospatial sciences, water... Development Center 3909 Halls Ferry Road Vicksburg, MS 39180-6199 Final report Approved for public release; distribution is unlimited

  9. 14 CFR Appendix I to Part 417 - Methodologies for Toxic Release Hazard Analysis and Operational Procedures

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... interrelationships, such as application of detection methodologies to provide early warning of releases and... spreads to one centimeter deep unless passive mitigation systems are in place that serve to contain the... release rate that is the total quantity divided by 10 unless passive mitigation systems are in place. (ii...

  10. 14 CFR Appendix I to Part 417 - Methodologies for Toxic Release Hazard Analysis and Operational Procedures

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... interrelationships, such as application of detection methodologies to provide early warning of releases and... spreads to one centimeter deep unless passive mitigation systems are in place that serve to contain the... release rate that is the total quantity divided by 10 unless passive mitigation systems are in place. (ii...

  11. 14 CFR Appendix I to Part 417 - Methodologies for Toxic Release Hazard Analysis and Operational Procedures

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... interrelationships, such as application of detection methodologies to provide early warning of releases and... spreads to one centimeter deep unless passive mitigation systems are in place that serve to contain the... release rate that is the total quantity divided by 10 unless passive mitigation systems are in place. (ii...

  12. 14 CFR Appendix I to Part 417 - Methodologies for Toxic Release Hazard Analysis and Operational Procedures

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... interrelationships, such as application of detection methodologies to provide early warning of releases and... spreads to one centimeter deep unless passive mitigation systems are in place that serve to contain the... release rate that is the total quantity divided by 10 unless passive mitigation systems are in place. (ii...

  13. 7 CFR 1486.303 - What specific contracting procedures must be adhered to?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS EMERGING MARKETS PROGRAM Program Operations § 1486.303 What specific contracting procedures must be adhered to? (a... an open manner. Individuals who develop or draft specifications, requirements, statements of...

  14. 14 CFR 151.27 - Procedures: Application, plans, specifications, and appraisals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., specifications, and appraisals. 151.27 Section 151.27 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Development Projects § 151.27 Procedures: Application, plans, specifications, and appraisals. (a) Except as... makes or obtains an appraisal of the interest. If the appraised value is less than the value placed...

  15. A Telomerase-Specific Doxorubicin-Releasing Molecular Beacon for Cancer Theranostics.

    PubMed

    Ma, Yi; Wang, Zhaohui; Zhang, Min; Han, Zhihao; Chen, Dan; Zhu, Qiuyun; Gao, Weidong; Qian, Zhiyu; Gu, Yueqing

    2016-03-01

    A molecular beacon-based drug delivery system was designed for both detection of telomerase activity in living cells and telomerase-triggered drug release for precise cancer treatment. This system is composed of a gold nanoparticle core densely packed with FITC-labeled hairpin DNA sequences hybridized with telomerase primers. Molecules of the anticancer drug doxorubicin were intercalated into the stem region of the DNA sequence. The presence of telomerase will elongate the primers, leading to inner chain substitution followed by the release of the FITC fluorescence and the trapped doxorubicin. This molecular beacon could specifically distinguish tumor cells and normal cells based on telomerase activity, precisely release doxorubicin in response to telomerase activity in the tumor cells, and prevent toxicity to normal organs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Measurement of acetylcholine released from rabbit detrusor smooth muscle using HPLC with electro-chemical detection coupled with microdialysis procedure.

    PubMed

    Inadome, A; Yoshida, M; Takahashi, W; Wada, Y; Kitani, K; Kikukawa, H; Yono, M; Seshita, H; Ueda, S

    1998-01-01

    We measured the amount of acetylcholine (ACh) released from rabbit detrusor smooth muscles induced by electrical field stimulation (EFS) using microdialysis procedure. The dialysis probe was inserted through the detrusor muscle strip and was continuously perfused with a Ringer solution containing physostigmine sulfate, at a rate of 2 microl/min. The strip was suspended in an organ bath filled with the modified Krebs-Henseleit solution and then EFS was delivered. The isometric force was recorded and monitored in each muscle preparation. The dialysates were collected every 10 min. ACh was determined by a high performance liquid chromatography with electro-chemical detection. The contraction of the muscle strip and ACh release induced by EFS were increased in a frequency and duration dependent manner. There were some differences between frequency response curves of contraction and frequency dependent ACh release. In the contractile response, the maximum contractions were observed at lower frequencies, while ACh releases reached the maximum at higher frequencies. There was a significant, but not simple correlation between EFS-induced contraction and ACh release. The results suggest that this new method is useful to investigate the ACh release from rabbit detrusor smooth muscles, and that other neurotransmitters than ACh possibly contribute to EFS-induced contraction.

  17. Enzymatic triggered release of an HIV-1 entry inhibitor from prostate specific antigen degradable microparticles.

    PubMed

    Clark, Meredith R; Aliyar, Hyder A; Lee, Chang-won; Jay, Julie I; Gupta, Kavita M; Watson, Karen M; Stewart, Russell J; Buckheit, Robert W; Kiser, Patrick F

    2011-07-15

    This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were loaded with the HIV-1 entry inhibitor sodium poly(styrene-4-sulfonate) (pSS). The particles were composed of N-2-hydroxyproplymethacrylamide and bis-methacrylamide functionalized peptides based on the PSA substrates GISSFYSSK and GISSQYSSK. Exposure to human seminal plasma (HSP) degraded the microgel network and triggered the release of the entrapped antiviral polymer. Particles with the crosslinker composed of the substrate GISSFYSSK showed 17 times faster degradation in seminal plasma than that of the crosslinker composed of GISSQYSSK. The microgel particles containing 1 mol% GISSFYSSK peptide crosslinker showed complete degradation in 30 h in the presence of HSP at 37°C and pSS released from the microgels within 30 min reached a concentration of 10 μg/mL, equivalent to the published IC(90) for pSS. The released pSS inactivated HIV-1 in the presence of HSP. The solid phase synthesis of the crosslinkers, preparation of the particles by inverse microemulsion polymerization, HSP-triggered release of pSS and inactivation of HIV-1 studies are described. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Enzymatic Triggered Release of an HIV-1 Entry Inhibitor from Prostate Specific Antigen Degradable Microparticles

    PubMed Central

    Clark, Meredith R.; Aliyar, Hyder A.; Lee, Chang-won; Jay, Julie I.; Gupta, Kavita M.; Watson, Karen M.; Stewart, Russell J.; Buckheit, Robert W.; Kiser, Patrick F.

    2011-01-01

    This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were loaded with the HIV-1 entry inhibitor sodium poly(styrene-4-sulfonate) (pSS). The particles were composed of N-2-hydroxyproplymethacrylamide and bis-methacrylamide functionalized peptides based on the PSA substrates GISSFYSSK and GISSQYSSK. Exposure to human seminal plasma (HSP) degraded the microgel network and triggered the release of the entrapped antiviral polymer. Particles with the crosslinker composed of the substrate GISSFYSSK showed 17 times faster degradation in seminal plasma than that of the crosslinker composed of GISSQYSSK. The microgel particles containing 1 mol% GISSFYSSK peptide crosslinker showed complete degradation in 30 hours in the presence of HSP at 37 °C and pSS released from the microgels within 30 minutes reached a concentration of 10 µg/mL, equivalent to the published IC90 for pSS. The released pSS inactivated HIV-1 in the presence of HSP. The solid phase synthesis of the crosslinkers, preparation of the particles by inverse microemulsion polymerization, HSP-triggered release of pSS and inactivation of HIV-1 studies are described. PMID:21511017

  19. A modified release analysis procedure using advanced froth flotation mechanisms. Technical report, September 1--November 30, 1995

    SciTech Connect

    Honaker, R.Q.; Mohanty, M.K.

    1995-12-31

    The objective of this study is to reinvestigate the release analysis procedure, which is traditionally conducted using a laboratory Denver cell, and to develop a modified process that can be used for all froth flotation technologies. Recent studies have found that the separation performance achieved by multiple stage cleaning and, in some cases, single stage cleaning using column flotation is superior to the performance achieved by the traditional release procedure. These findings are a result of the advanced flotation mechanisms provided by column flotation, which will be incorporated into a modified release analysis procedure developed in this study. A fundamental model of an open column has been developed which incorporates the effects of system hydrodynamics, froth drop-back, selective and non-selective detachment, operating parameters, feed solids content, and feed component flotation kinetics. Simulation results obtained during this reporting period indicate that the ultimate separation that can be achieved by a column flotation process can only be obtained in a single cleaning stage if the detachment mechanism in the froth phase is highly selective, which does not appear to occur in practice based on experimental results. Two to three cleaning stages were found to be required to obtain the ultimate performance if non-selective detachment or kinetic limiting conditions are assumed. this simulated finding agrees well with the experimental results obtained from the multiple stage cleaning of an Illinois No. 5 seam coal using the Packed-Column. Simulated results also indicate that the separation performance achieved by column flotation improves with increasing feed solids content after carrying-capacity limiting conditions are realized. These findings will be utilized in the next reporting period to modify the traditional release analysis procedure.

  20. Literature Review of Cosmetic Procedures in Men: Approaches and Techniques are Gender Specific.

    PubMed

    Cohen, Brandon E; Bashey, Sameer; Wysong, Ashley

    2017-02-01

    The proportion of men receiving non-surgical cosmetic procedures has risen substantially in recent years. Various physiologic, anatomic, and motivational considerations differentiate the treatments for male and female patients. Nevertheless, research regarding approaches to the male cosmetic patient is scarce. We sought to provide an overview and sex-specific discussion of the most popular cosmetic dermatologic procedures pursued by men by conducting a comprehensive literature review pertaining to non-surgical cosmetic procedures in male patients. The most common and rapidly expanding non-surgical interventions in men include botulinum toxin, filler injection, chemical peels, microdermabrasion, laser resurfacing, laser hair removal, hair transplantation, and minimally invasive techniques for adipose tissue reduction. Important sex-specific factors associated with each of these procedures should be considered to best serve the male cosmetic patient.

  1. A modified release analysis procedure using advanced froth flotation mechanisms: Technical report, March 1, 1996-May 31, 1996

    SciTech Connect

    Honaker, R.Q., Mohanty, M.K.

    1997-04-01

    Recent studies indicate that the optimum separation performances achieved by multiple stage cleaning using various column flotation technologies and single stage cleaning using a Packed-Flotation Column are superior to the performance achieved by the traditional release procedure, especially in terms of pyritic sulfur rejection. This superior performance is believed to be the result of the advanced flotation mechanisms provided by column flotation technologies. Thus, the objective of this study is to develop a suitable process utilizing the advanced froth flotation mechanisms to characterize the true flotation response of a coal sample. Work in this reporting period concentrated on developing a modified coal flotation characterization procedure, termed as Advanced Flotation Washability (AFW) technique. The new apparatus used for this procedure is essentially a batch operated packed-column device equipped with a controlled wash water system. Several experiments were conducted using the AFW technique on a relatively high sulfur, -100 mesh Illinois No. 5 run-of-mine coal sample collected from a local coal preparation plant. Similar coal characterization experiments were also conducted using the traditional release and tree analysis procedures. The best performance curve generated using the AFW technique was found to be superior to the optimum curve produced by the traditional procedures. For example, at a combustible recovery of 80%, a 19% improvement in the reduction of the pyritic sulfur content was achieved by the AFW method while the ash reduction was also enhanced by 4%. Several tests are on-going to solidify the AFW procedure and verify the above finding by conducting Anova analyses to evaluate the repeatability of the AFW method and the statistical significance of the difference in the performance achieved from the traditional and modified coal characterization procedures.

  2. Evaluation of Approval Request 47; Call for Release Procedures for Charlotte Douglas International Airport

    NASA Technical Reports Server (NTRS)

    Stevens, Lindsay; Martin, Lynne; Jobe, Kimberly; Parke, Bonny; Chevalley, Eric; Lee, Hanbong; Verma, Savita; Dulchinos, Victoria

    2017-01-01

    NASA is collaborating with the Federal Aviation Administration (FAA) and aviation industry partners to develop and demonstrate new concepts and technologies for Integrated Arrival, Departure, and Surface (IADS) traffic management capabilities under the Airspace Technology Demonstration 2 (ATD-2) project. One of the goals of the IADS capabilities in the ATD-2 project is to increase predictability and throughput of airspace operations by improving Traffic Management Initiative (TMI) compliance. This paper focuses on the Approval Request (APREQ) procedures developed for the ATD-2 project between the Air Traffic Control (ATC) Tower at Charlotte Douglas International Airport and Washington Center. In March 2017, NASA conducted a Human-in-the-Loop (HITL) simulation to evaluate the operational procedures and information requirements for the APREQ procedures in the ATD-2 IADS system between ATC Tower and Center. The findings from the HITL are used to compare ATD-2 APREQ procedures with information about current day APREQ procedures.

  3. Multifunctional liposomes having target specificity, temperature-triggered release, and near-infrared fluorescence imaging for tumor-specific chemotherapy.

    PubMed

    Kono, Kenji; Takashima, Munenobu; Yuba, Eiji; Harada, Atsushi; Hiramatsu, Yoshie; Kitagawa, Hiroyuki; Otani, Takayuki; Maruyama, Kazuo; Aoshima, Sadahito

    2015-10-28

    We designed functional liposomes with target specificity, temperature-triggered drug release, and near-infrared fluorescence imaging. We prepared the liposomes by triple functionalization of stable pegylated liposomes with thermosensitive poly[2-(2-ethoxy)ethoxyethyl vinyl ether] chains (lower critical solution temperature around 38 °C) with conjugation of antibody trastuzumab (Herceptin, HER), which targets human epidermal growth factor 2, and with incorporation of indocyanine green for near-infrared fluorescence imaging. The liposomes retained DOX in the interior below physiological temperature but released DOX immediately at temperatures higher than 40 °C. The liposomes exhibited excellent ability for association and internalization to target cells overexpressing Her-2, such as SK-OV3 and SB-BR3 cells, and killed these cells when heated at 45 °C for 5 min. When administered intravenously to mice bearing SK-OV3 tumor, the liposomes having HER accumulated in the tumor more efficiently than the liposomes without HER. They stayed there more than 48 h, as judged with near-infrared fluorescence imaging. Furthermore, when the tumor sites of the mice being administered with the DOX-loaded liposomes were heated mildly at 44°C for 10 min at 7h after administration, tumor growth was suppressed strongly thereafter. Treatment with the HER-conjugated liposomes produced more efficient tumor-suppressive effects. Results demonstrate that the synergy of target-specific association, temperature-triggered drug release, and imaging is important for efficient tumor chemotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Hydrophobically modified alginate hydrogels as protein carriers with specific controlled release properties.

    PubMed

    Leonard, M; De Boisseson, M Rastello; Hubert, P; Dalençon, F; Dellacherie, E

    2004-08-27

    Amphiphilic derivatives of sodium alginate, prepared by chemical covalent binding of long alkyl chains onto the polysaccharide backbone via ester functions, form strong hydrogels in aqueous solutions. The shear-thinning and thixotropic behaviors of these hydrogels have been exploited to prepare particles (millimetric beads or microparticles) by dispersion in sodium chloride solutions. This all-aqueous procedure was used for the encapsulation of model proteins, such as bovine serum albumin (BSA) and human hemoglobin (Hb), or of a vaccine protein (Helicobacter pylori (H. pylori) urease). In all cases, the encapsulation yields were very high (70-100%). No release of model proteins was observed in water within several days, in contrast with protein-loaded calcium alginate particles, which exhibit an important release within only a few hours. The controlled release of proteins can, however, be achieved by inducing the dissociation of the physical hydrophobic network. This dissociation has been obtained either by addition of surfactants, acting as disrupting agents of intermolecular hydrophobic junctions, or of esterases such as lipases, which hydrolyze the ester bond between alkyl chains and the polysaccharide backbone. The level of immunization against H. pylori infection in mice, induced by encapsulated urease administrated by either systemic or mucosal routes, was also assessed.

  5. A framework to investigate drug release variability arising from hypromellose viscosity specifications in controlled release matrix tablets.

    PubMed

    Mitchell, Shawn A; Balwinski, Karen M

    2008-06-01

    Substitution level, particle size, and molecular weight are key properties of hypromellose (HPMC) known to be important to its performance in pharmaceutical-controlled release applications. The hypromellose monographs indirectly specify acceptable ranges for the molecular weight of HPMC products, expressed as the apparent viscosity of a 2% aqueous solution. The purpose of this study was to provide a framework to systematically investigate the amount of drug release variability that might be expected for typical controlled release formulations over the monograph viscosity ranges for hypromellose. An approach to estimate the expected drug release variability was developed based on scaling laws in the literature. New experimental data were generated with pentoxifylline, theophylline, and hydrochlorothiazide as model drugs to explore the applicability of this approach to a range of formulations. This methodology predicted that drug release variability over the United States Pharmacopeia (USP) viscosity ranges would be greatest for the lower viscosity grades of hypromellose, such as E50 and K100 LV. Drug release variability due to hypromellose viscosity variations is expected to be larger for formulations having substantial contributions from erosional drug release, and smaller for formulations with a predominantly diffusional drug release mechanism. These predictions need to be validated experimentally.

  6. Target-specific suppression of GABA release from parvalbumin interneurons in the basolateral amygdala by dopamine.

    PubMed

    Chu, Hong-Yuan; Ito, Wataru; Li, Jiayang; Morozov, Alexei

    2012-10-17

    Dopamine (DA) in the basolateral amygdala (BLA) promotes fear learning by disinhibiting principal neurons (PNs) and enabling synaptic plasticity in their sensory inputs. While BLA interneurons (INs) are heterogeneous, it is unclear which interneuron subtypes decrease GABAergic input to PNs in the presence of DA. Here, using cell type-selective photostimulation by channelrhodopsin 2 in BLA slices from mouse brain, we examined the role of parvalbumin-positive INs (PV-INs), the major interneuronal subpopulation in BLA, in the disinhibitory effect of DA. We found that DA selectively suppressed GABAergic transmission from PV-INs to PNs by acting on presynaptic D(2) receptors, and this effect was mimicked by Rp-cAMP, an inhibitor of cAMP-dependent signaling. In contrast, DA did not alter GABA release from PV-INs to INs. Furthermore, neither suppressing cAMP-dependent signaling by Rp-cAMP nor enhancing it by forskolin altered GABA release from PV-INs to BLA INs. Overall, DA disinhibits BLA, at least in part, by suppressing GABA release from PV-INs in the target cell-specific manner that results from differential control of this release by cAMP-dependent signaling.

  7. Murine macrophage interleukin-1 release by capsularlike serotype-specific polysaccharide antigens of Actinobacillus actinomycetemcomitans.

    PubMed Central

    Takahashi, T; Nishihara, T; Ishihara, Y; Amano, K; Shibuya, N; Moro, I; Koga, T

    1991-01-01

    Serotype-specific polysaccharide antigens (SPAs) were extracted from whole cells of Actinobacillus actinomycetemcomitans ATCC 29523 (serotype a), Y4 (serotype b), and NCTC 9710 (serotype c) by autoclaving and purified by chromatography on DEAE-Sephadex A-25 and Sephacryl S-300 columns. Y4 SPA induced interleukin-1 (IL-1) release by P388D1 murine macrophages. Polymyxin B had virtually no effect on the release of IL-1. Rabbit anti-murine IL-1 serum strongly suppressed the proliferation of C3H/HeJ mouse thymocytes induced with the culture supernatants of Y4 SPA-stimulated P388D1 cells and a submitogenic dose of concanavalin A. Gel filtration of the culture supernatants of Y4 SPA-stimulated macrophages on Sephacryl S-200 showed that an IL-1 peak at a point corresponding to approximately 16.5 kDa was eluted. The ability of SPAs from strains ATCC 29523 and NCTC 9710 to induce the release of IL-1 was lower than that of Y4 SPA. The IL-1-releasing ability of serotype a and c antigens was enhanced by deacetylation of both polysaccharides, suggesting that acetyl groups of these antigens might hinder the interaction between the antigens and macrophages. PMID:1987032

  8. 50 CFR Appendix F to Part 622 - Specifications for Sea Turtle Mitigation Gear and Sea Turtle Handling and Release Requirements

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Specifications for Sea Turtle Mitigation Gear and Sea Turtle Handling and Release Requirements F Appendix F to Part 622 Wildlife and Fisheries... 622—Specifications for Sea Turtle Mitigation Gear and Sea Turtle Handling and Release Requirements...

  9. Patient-specific endovascular simulation influences interventionalists performing carotid artery stenting procedures.

    PubMed

    Willaert, W I M; Aggarwal, R; Van Herzeele, I; O'Donoghue, K; Gaines, P A; Darzi, A W; Vermassen, F E; Cheshire, N J

    2011-04-01

    The ability to perform patient-specific simulated rehearsal of complex endovascular interventions is a technological advance with potential benefits to patient outcomes. This study aimed to evaluate whether patient-specific rehearsal of a carotid artery stenting (CAS) procedure has an influence on tool selection and the use of fluoroscopy. Following case note and computed tomography (CT) angiographic review of a real patient case, subjects performed the CAS procedure on a virtual reality simulator. Endovascular tool requirements and fluoroscopic angles were evaluated with a pre- and post-case questionnaire. Participants also rated the simulation from 1 (poor) to 5 (excellent). Thirty-three endovascular physicians with varying degrees of CAS experience were recruited: inexperienced (5-20 CAS procedures) n = 11, moderately (21-50 CAS procedures) n = 7 or highly experienced (>50 CAS procedures) n = 15. For all participants, 96 of a possible 363 changes (26%) were observed from pre- to post-case questionnaires. This was most notable for optimal fluoroscopy C-arm position 15/33 (46%), choice of selective catheter 13/33 (39%), choice of sheath or guiding catheter 11/33 (33%) and balloon dilatation strategy 10/33 (30%). Experience with the CAS procedure did not influence the degree of change significantly (p > 0.05), and all groups exhibited a considerable modification in tool and fluoroscopy preference. The model was considered realistic and useful as a tool to practice a real case (median score 4/5). Patient-specific simulated rehearsal of a complex endovascular procedure strongly influences tool selection and fluoroscopy preferences for the real case. Further research has to evaluate how this technology may transfer from in vitro to in vivo and if it can reduce the radiation dose and the number of endovascular tools used and improve outcomes for patients in the clinical setting. Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All

  10. 7 CFR 1486.303 - What specific contracting procedures must be adhered to?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS EMERGING MARKETS PROGRAM Program Operations § 1486.303 What specific contracting procedures must be adhered to? (a...) Perform some form of fee, price, or cost analysis, such as a comparison of price quotations to market...

  11. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Supplementary specific procedural... stoves. 200.936 Section 200.936 Housing and Urban Development Regulations Relating to Housing and Urban... HOUSING AND URBAN DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Minimum Property Standards §...

  12. Ohio Guidelines for the Identification of Children with Specific Learning Disabilities (Including Differentiated Referral Procedures).

    ERIC Educational Resources Information Center

    Cuyahoga Special Education Service Center, Maple Heights, OH.

    The guidelines focus on procedures for determining eligibility for services of children with specific learning disabilities. A 13-step process is delineated from the classroom teacher's response to individual learner needs through multifactored evaluation team function to annual review and reevaluation. Throughout the process, special emphasis is…

  13. 7 CFR 1484.35 - Must Cooperators follow specific contracting procedures?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Must Cooperators follow specific contracting procedures? 1484.35 Section 1484.35 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS PROGRAMS TO HELP DEVELOP...

  14. 7 CFR 1484.35 - Must Cooperators follow specific contracting procedures?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Must Cooperators follow specific contracting procedures? 1484.35 Section 1484.35 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS PROGRAMS TO HELP DEVELOP...

  15. 7 CFR 1484.35 - Must Cooperators follow specific contracting procedures?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Must Cooperators follow specific contracting procedures? 1484.35 Section 1484.35 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS PROGRAMS TO HELP DEVELOP...

  16. 40 CFR 63.7521 - What fuel analyses, fuel specification, and procedures must I use?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... fuel specification analyses for hydrogen sulfide and mercury according to the procedures in paragraphs... expected minimum detection levels, to be used for the measurement of hydrogen sulfide and mercury. (v) If... mercury, in units of microgram per cubic meter, and of hydrogen sulfide, in units of parts per million,...

  17. 40 CFR 63.7521 - What fuel analyses, fuel specification, and procedures must I use?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... fuel specification analyses for hydrogen sulfide and mercury according to the procedures in paragraphs... expected minimum detection levels, to be used for the measurement of hydrogen sulfide and mercury. (v) If... mercury, in units of microgram per cubic meter, and of hydrogen sulfide, in units of parts per million,...

  18. Field Operations and Enforcement Manual for Air Pollution Control. Volume III: Inspection Procedures for Specific Industries.

    ERIC Educational Resources Information Center

    Weisburd, Melvin I.

    The Field Operations and Enforcement Manual for Air Pollution Control, Volume III, explains in detail the following: inspection procedures for specific sources, kraft pulp mills, animal rendering, steel mill furnaces, coking operations, petroleum refineries, chemical plants, non-ferrous smelting and refining, foundries, cement plants, aluminum…

  19. Procedural and Declarative Memory in Children with and without Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Gelgic, Celin; Conti-Ramsden, Gina

    2010-01-01

    Background: Much evidence has accumulated to indicate memory deficits in children with specific language impairment. However, most research has focused on working memory impairments in these children. Less is known about the functioning of other memory systems in this population. Aims: This study examined procedural and declarative memory in young…

  20. Declarative and Procedural Memory in Danish Speaking Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Bleses, Dorthe

    2012-01-01

    It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge…

  1. Field Operations and Enforcement Manual for Air Pollution Control. Volume III: Inspection Procedures for Specific Industries.

    ERIC Educational Resources Information Center

    Weisburd, Melvin I.

    The Field Operations and Enforcement Manual for Air Pollution Control, Volume III, explains in detail the following: inspection procedures for specific sources, kraft pulp mills, animal rendering, steel mill furnaces, coking operations, petroleum refineries, chemical plants, non-ferrous smelting and refining, foundries, cement plants, aluminum…

  2. Evidence for specific secretion rather than autolysis in the release of some Helicobacter pylori proteins.

    PubMed

    Vanet, A; Labigne, A

    1998-03-01

    We investigated whether Helicobacter pylori cells actively secrete proteins such as the urease subunits UreA and UreB and the GroES and GroEL homologs HspA and HspB or whether these proteins were present in the extracellular compartment as a consequence of autolysis. Using a subcellular fractionation approach associated with quantitative Western blot analyses, we showed that the supernatant protein profiles were very different from those of the cell pellets, even for bacteria harvested in the late growth phase; this suggests that the release process is selective. A typical cytoplasmic protein, a beta-galactosidase homolog, was found exclusively associated with the pellet of whole-cell extracts, and no traces were found in the supernatant. In contrast, UreA, UreB, HspA, and HspB were mostly found in the pellet but significant amounts were also present in the supernatant. HspA and UreB were released into the supernatant at the same rate throughout the growth phase (3%), whereas large portions of HspB and UreA were released during the stationary phase (over 30 and 20%, respectively) rather than during the early growth phase (20% and 6, respectively). The profiles of protein obtained after water extraction of the bacteria with those of the proteins naturally released within the liquid culture supernatants demonstrated that water extraction led to the release of a large amount of protein due to artifactual lysis. Our data support the conclusion that a specific and selective mechanism(s) is involved in the secretion of some H. pylori antigens. A programmed autolysis process does not seem to make a major contribution.

  3. A Smart Capsule With GI-Tract-Location-Specific Payload Release.

    PubMed

    Yu, Wuyang; Rahimi, Rahim; Ochoa, Manuel; Pinal, Rodolfo; Ziaie, Babak

    2015-09-01

    In this paper, we present a smart capsule for location-specific drug release in the gastrointestinal tract. Once activated through a magnetic proximity fuse, the capsule opens up and releases its powdered payload in a location specified by an implanted miniature magnetic marker or an externally worn larger magnet. The capsule (9 mm × 26 mm) comprises of two compartments: one contains a charged capacitor and a reed switch, while the second one houses the drug reservoir capped by a taut nylon thread intertwined with a nichrome wire. The nichrome wire is connected to the capacitor through the reed switch. The capacitor is charged to 2.7 V before ingestion and once within the proximity of the permanent magnet; the reed switch closes, discharging the capacitor through the nichrome wire, melting the nylon thread, detaching the cap, and emptying the drug reservoir.

  4. Setting radon-specific release criteria and demonstrating compliance for land affected by NORM.

    PubMed

    García-Talavera, M; Martínez, M; Matarranz, J L M; Ramos, L

    2008-11-01

    Residues from industrial activities involving naturally occurring radioactive materials (NORMs) may cause radiation exposures to members of the public, particularly when NORM-affected land is brought into residential use. To provide an adequate protection against radiation in such situations, the following limiting criteria are currently required in Spain for releasing NORM-affected land: (i) no more than a 300 microSv yr(-1) increase (excluding radon doses) over the natural background; (ii) (222)Rn concentrations in hypothetical future dwellings lower than 200 Bq m(-3); and (iii) reduction of all radiation exposures to as low as reasonable achievable. This paper addresses some of the problems encountered in translating the (222)Rn criterion into site-specific release limits and in demonstrating compliance with them.

  5. A review of 105 consecutive uniport endoscopic plantar fascial release procedures for the treatment of chronic plantar fasciitis.

    PubMed

    Morton, Troy N; Zimmerman, Jeffrey P; Lee, Michael; Schaber, John D

    2013-01-01

    Plantar fasciitis is a common cause of heel pain in the U.S. Army soldier, resulting in a significant loss of man hours. Given the heavy operations tempo of the U.S. military, successful treatment options need to be considered and used as quickly as possible. Plantar fasciitis can be successfully treated in up to 90% of patients using conservative measures. Operative intervention might need to be considered for those in whom conservative measures have failed. The present report is a review of 105 consecutive uniport endoscopic plantar fascial release procedures performed by the principal investigator during a 9-year period. The following data were collected and analyzed: gender, age, weight, height, body mass index, medical treatment facility, procedure laterality, preoperative pain levels, postoperative pain levels at 3 months, first ambulatory day in the controlled ankle motion boot, return to activity as tolerated, and complications. Three major points were of interest: evidence of improvement in chronic plantar fasciitis when treated with uniport endoscopic procedures; the patient attributes associated with self-reported pain levels 90 days postoperatively; and the patient attributes associated with the average time until patients were able to return to activities as tolerated in a controlled ankle motion boot. It was noted that 44.5% of those with a body mass index of 29.80 kg/m(2) or greater reported a postoperative pain level of 0; and 96.3% of those with a body mass index of 25.53 kg/m(2) or less reported postoperative pain levels of 0. The analyzed data were used to characterize the clinical outcomes of the procedure, identify changes in outcome with surgeon experience, and identify whether certain patient subgroups have better outcomes, allowing surgeons to identify which patient might be the best candidates for an endoscopic release procedure.

  6. Release of vanadium from oxidized sediments: insights from different extraction and leaching procedures.

    PubMed

    Cappuyns, V; Swennen, R

    2014-02-01

    Although the attention for vanadium (V) as a potentially harmful element is growing and some countries adopted threshold values for V in soils, sediments, groundwater, or surface water, V is generally of little importance in environmental legislation and the knowledge about the behavior of V in the environment is still limited. In the present study, the release of V from oxidized sediments, sediment-derived soils, and certified reference materials was investigated by means of several types of leaching tests and extractions that are frequently used for soil and sediment characterization. The pHstat leaching tests and single and sequential extractions applied in this study show that V generally displays a very limited actual and potential mobility in sediment. "Mobile" V concentrations, as estimated by the amount of V released by a single extraction with CaCl2 0.01 mol L(-1), were low, even in the most contaminated sediment samples. Only under strongly acidifying conditions (pH 2), such as in the case of ingestion of soil or sediment or in accidental spills, a substantial release of V can be expected.

  7. Diazepam-induced release of behavior in an extinction procedure: its reversal by Ro 15-1788.

    PubMed

    Thiébot, M H; Childs, M; Soubrié, P; Simon, P

    1983-03-18

    The effects of the benzodiazepine receptor antagonist Ro 15-1788, an imidazobenzodiazepine derivative, were studied with respect to three pharmacological activities exerted by diazepam in rats. Two of these, release of shock-induced suppression of drinking and attenuation of non-reward-induced cessation of responding for food, reflect the anxiolytic property of benzodiazepines. The amnesic-like effect of diazepam was also investigated. Ro 15-1788 (in doses ranging from 4 to 16 mg/kg p.o.) completely reversed diazepam (2 mg/kg)-induced release of behavior in both punishment and non-reward procedures. In contrast, Ro 15-1788 reduced but did not completely abolish diazepam-induced amnesia. These data suggest that the anticonflict and anti-frustration effects of benzodiazepines probably involve similar receptor types which nevertheless differ from those chiefly implicated in the amnesic-like activity of benzodiazepines.

  8. 32 CFR 1656.16 - Early release-grounds and procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... based on a physical or mental examination at a MEPS or other location designated by Selective Service... Section 1656.16 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM ALTERNATIVE SERVICE § 1656.16 Early release—grounds and procedures. (a) General Rule of Service Completion....

  9. Parting ways: parasite release in nature leads to sex-specific evolution of defence.

    PubMed

    Dargent, F; Rolshausen, G; Hendry, A P; Scott, M E; Fussmann, G F

    2016-01-01

    We evaluated the extent to which males and females evolve along similar or different trajectories in response to the same environmental shift. Specifically, we used replicate experimental introductions in nature to consider how release from a key parasite (Gyrodactylus) generates similar or different defence evolution in male vs. female guppies (Poecilia reticulata). After 4-8 generations of evolution, guppies were collected from the ancestral (parasite still present) and derived (parasite now absent) populations and bred for two generations in the laboratory to control for nongenetic effects. These F2 guppies were then individually infected with Gyrodactylus, and infection dynamics were monitored on each fish. We found that parasite release in nature led to sex-specific evolutionary responses: males did not show much evolution of resistance, whereas females showed the evolution of increased resistance. Given that male guppies in the ancestral population had greater resistance to Gyrodactylus than did females, evolution in the derived populations led to reduction of sexual dimorphism in resistance. We argue that previous selection for high resistance in males constrained (relative to females) further evolution of the trait. We advocate more experiments considering sex-specific evolutionary responses to environmental change. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  10. The relation between receptive grammar and procedural, declarative, and working memory in specific language impairment.

    PubMed

    Conti-Ramsden, Gina; Ullman, Michael T; Lum, Jarrad A G

    2015-01-01

    What memory systems underlie grammar in children, and do these differ between typically developing (TD) children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which procedural, declarative, and working memory abilities predict receptive grammar in 45 primary school aged children with SLI (30 males, 15 females) and 46 TD children (30 males, 16 females), both on average 9;10 years of age. Regression analyses probed measures of all three memory systems simultaneously as potential predictors of receptive grammar. The model was significant, explaining 51.6% of the variance. There was a significant main effect of learning in procedural memory and a significant group × procedural learning interaction. Further investigation of the interaction revealed that procedural learning predicted grammar in TD but not in children with SLI. Indeed, procedural learning was the only predictor of grammar in TD. In contrast, only learning in declarative memory significantly predicted grammar in SLI. Thus, different memory systems are associated with receptive grammar abilities in children with SLI and their TD peers. This study is, to our knowledge, the first to demonstrate a significant group by memory system interaction in predicting grammar in children with SLI and their TD peers. In line with Ullman's Declarative/Procedural model of language and procedural deficit hypothesis of SLI, variability in understanding sentences of varying grammatical complexity appears to be associated with variability in procedural memory abilities in TD children, but with declarative memory, as an apparent compensatory mechanism, in children with SLI.

  11. The relation between receptive grammar and procedural, declarative, and working memory in specific language impairment

    PubMed Central

    Conti-Ramsden, Gina; Ullman, Michael T.; Lum, Jarrad A. G.

    2015-01-01

    What memory systems underlie grammar in children, and do these differ between typically developing (TD) children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which procedural, declarative, and working memory abilities predict receptive grammar in 45 primary school aged children with SLI (30 males, 15 females) and 46 TD children (30 males, 16 females), both on average 9;10 years of age. Regression analyses probed measures of all three memory systems simultaneously as potential predictors of receptive grammar. The model was significant, explaining 51.6% of the variance. There was a significant main effect of learning in procedural memory and a significant group × procedural learning interaction. Further investigation of the interaction revealed that procedural learning predicted grammar in TD but not in children with SLI. Indeed, procedural learning was the only predictor of grammar in TD. In contrast, only learning in declarative memory significantly predicted grammar in SLI. Thus, different memory systems are associated with receptive grammar abilities in children with SLI and their TD peers. This study is, to our knowledge, the first to demonstrate a significant group by memory system interaction in predicting grammar in children with SLI and their TD peers. In line with Ullman’s Declarative/Procedural model of language and procedural deficit hypothesis of SLI, variability in understanding sentences of varying grammatical complexity appears to be associated with variability in procedural memory abilities in TD children, but with declarative memory, as an apparent compensatory mechanism, in children with SLI. PMID:26284013

  12. National Trends in Carpal Tunnel Release and Hand Fracture Procedures Performed During Orthopaedic Residency: An Analysis of ACGME Case Logs

    PubMed Central

    Hinds, Richard M.; Gottschalk, Michael B.; Capo, John T.

    2016-01-01

    Background  Mastery in performing carpal tunnel release (CTR) and hand fracture procedures is an essential component of orthopaedic residency training. Objective  To assess orthopaedic resident case log data for temporal trends in CTR and hand fracture cases and to determine the degree of variability in case volume among residents. Methods  Accreditation Council for Graduate Medical Education orthopaedic surgery resident case logs were reviewed for graduation years 2007 through 2014. Annual data regarding the mean number of CTR and hand fracture/dislocation procedures were recorded, as well as the median number of procedures reported by the top and bottom 10% of residents (by case volume). Temporal trends were assessed using linear regression modeling. Results  There was no change in the mean number of CTRs performed per resident. Over the 8-year period, the top 10% of residents performed a significantly greater number of CTRs than the bottom 10% (62.1 versus 9.3, P < .001). Similarly, no change was noted in the mean number of total hand fracture/dislocation cases performed, with the top 10% of residents performing significantly more hand fracture cases than the bottom 10% (47.1 versus 9.3, P < .001). Conclusions  Our results indicate no change in CTR and hand fracture caseload for orthopaedic residents. However, as resident experience performing both procedures varies significantly, this variability likely has important educational implications. PMID:26913105

  13. An effect of modeling and imitation teaching procedures on children with and without specific language impairment.

    PubMed

    Connell, P J

    1987-03-01

    Following a treatment program in which an invented morpheme was taught through either imitation or modeling procedures, the generalization of 40 specific language-impaired children was compared to that of 40 children learning language normally. The results of the comparison indicated that the two teaching procedures have opposite relative effects on the two groups. The abnormal group generalized more extensively following imitation teaching while the normal group generalized more extensively following modeling teaching. The opposing results of the two procedures on the two groups suggest that language-impaired children will benefit more from teaching strategies that are adapted to their unique learning styles than from strategies fashioned after the styles of children who learn language normally.

  14. Developing patient-specific anatomic models for validation of cardiac ablation guidance procedures

    NASA Astrophysics Data System (ADS)

    Holmes, David, III; Rettmann, Maryam; Cameron, Bruce; Camp, Jon; Robb, Richard

    2008-03-01

    Image-guided cardiac ablation has the potential to decrease procedure times and improve clinical outcome for patients with cardiac arrhythmias. There are several proposed methods for integrating patient-specific anatomy into the cardiac ablation procedure; however, these methods require thorough validation. One of the primary challenges in validation is determining ground truth as a standard for comparison. Some validation protocols have been developed for animals models and even in patients; however, these methods can be costly to implement and may increase the risk to patients. We have developed an approach to building realistic patient-specific anatomic models at a low-cost in order to validate the guidance procedure without introducing additional risk to the patients. Using a pre-procedural cardiac computed tomography scan, the blood pool of the left and right atria of a patient are segmented semi-manually. In addition, several anatomical landmarks are identified in the image data. The segmented atria and landmarks are converted into a polygonalized model which is used to build a thin-walled patient-specific blood pool model in a stereo-lithography system. Thumbscrews are inserted into the model at the landmarks. The entire model is embedded in a platinum silicone material which has been shown to have tissue-mimicking properties relative to ultrasound. Once the pliable mold has set, the blood pool model is extracted by dissolving the rigid material. The resulting physical model correctly mimics a specific patient anatomy with embedded fiducals which can be used for validation experiments. The patient-specific anatomic model approach may also be used for pre-surgical practice and training of new interventionalists.

  15. Procedural specificity in laparoscopic simulator training: protocol for a randomised educational superiority trial.

    PubMed

    Bjerrum, Flemming; Sorensen, Jette Led; Konge, Lars; Lindschou, Jane; Rosthøj, Susanne; Ottesen, Bent; Strandbygaard, Jeanett

    2014-10-10

    The use of structured curricula for minimally invasive surgery training is becoming increasingly popular. However, many laparoscopic training programs still use basic skills and isolated task training, despite increasing evidence to support the use of training models with higher functional resemblance, such as whole procedural modules. In contrast to basic skills training, procedural training involves several cognitive skills such as elements of planning, movement integration, and how to avoid adverse events. The objective of this trial is to investigate the specificity of procedural practice in laparoscopic simulator training. A randomised single-centre educational superiority trial. Participants are 96 surgical novices (medical students) without prior laparoscopic experience. Participants start by practicing a series of basic skills tasks to a predefined proficiency level on a virtual reality laparoscopy simulator. Upon reaching proficiency, the participants are randomised to either the intervention group, which practices two procedures (an appendectomy followed by a salpingectomy) or to the control group, practicing only one procedure (a salpingectomy) on the simulator. 1:1 central randomisation is used and participants are stratified by sex and time to complete the basic skills. Data collection is done at a surgical skills centre.The primary outcome is the number of repetitions required to reach a predefined proficiency level on the salpingectomy module. The secondary outcome is the total training time to proficiency. The improvement in motor skills and effect on cognitive load are also explored. The results of this trial might provide new knowledge on how the technical part of surgical training curricula should be comprised in the future. To examine the specificity of practice in procedural simulator training is of great importance in order to develop more comprehensive surgical curricula. ClinicalTrials.gov: NCT02069951.

  16. [Recommendations for Releasing the Pelvic Binder After a Non-Invasive Pelvic Stabilisation Procedure Under Emergency Room Conditions].

    PubMed

    Schweigkofler, U; Wohlrath, B; Paffrath, T; Flohé, S; Wincheringer, D; Hoffmann, R; Trentzsch, H

    2016-10-01

    kinematics. 2) Assessment of the haemodynamic status. 3) Check of the need to open the pelvic binder for diagnostic/therapeutic measures before completing all diagnostic tests. 4) Assessment of the radiology diagnostic testing and release of the pelvic region. The result is a so-called "clear the pelvis algorithm" which describes a structured approach according to specific criteria and which specifies the circumstances under which the pelvic binder can be opened. Additional studies are necessary to analyse the applicability and safety of this algorithm in a clinical context. Our advice is not to "clear" the pelvis if no X-rays or CT scans of the pelvis have been carried out without (or with an opened) pelvic binder.

  17. Aspects of grammar sensitive to procedural memory deficits in children with specific language impairment.

    PubMed

    Sengottuvel, Kuppuraj; Rao, Prema K S

    2013-10-01

    Procedural deficit hypothesis claims that language deficit in children with specific language impairment is affiliated to sequence learning problems. However, studies did not explore on aspects of grammar vulnerable to sequence learning deficits. The present study makes predictions for aspects of grammar that could be sensitive to procedural deficits based on core ideas of procedural deficit hypothesis. The hypothesis for the present study was that the grammatical operations that require greater sequencing abilities (such as inflectional operations) would be more affected in children with language impairment. Further, the influence of sequencing difficulties would be even greater in agglutinating inflectional languages. An adapted serial reaction time task for sequence learning measurements along with grammatical tasks on derivation, inflection, and sentence complexity were examined on typically developing and language impaired children. Results were in favor of procedural deficit hypothesis and its close relation to non-adjacent grammatical operations. The findings were discussed using procedural deficits, declarative compensatory mechanism, and statistical learning deficits. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Comparison of 1997 Medicare relative value units for gender-specific procedures: is Adam still worth more than Eve?

    PubMed

    Goff, B A; Muntz, H G; Cain, J M

    1997-08-01

    On January 1, 1992, Congress implemented a Medicare payment system based on relative value units (RVUs). The total RVU (which is made up of work, practice, and malpractice RVUs) is multiplied by a dollar conversion factor to set the reimbursement for all procedures covered by Medicare. In a previous study, we found that significant gender bias exists in Medicare reimbursement for female-specific services. Recently, HCFA approved increases (beginning January 1997) in the work RVU for many gynecologic procedures. This study was undertaken to compare work and total RVUs for gender-specific procedures effective January 1, 1997. Using the May 1996 Federal Register, we compared work and total RVUs for 24 pairs of gender-specific procedures. The groups were matched so that the amount of work and level of difficulty would be similar, if not identical. We validated our selection of procedures for comparison by also evaluating the average time required to perform these procedures. Comparison of work RVUs for the 24 paired procedures revealed that in 19 cases (80%), male-specific procedures had a higher RVU; in 3 cases (12%), female-specific procedures were higher; and in 2 cases, there was no difference. On average, work RVUs were 49% higher for urologic procedures than for gynecologic procedures. Comparison of total RVUs revealed that in 20 cases (83%), urologic procedures had a higher total RVU and in 3 cases (12%), gynecologic procedures were higher. On average, male-specific surgeries are reimbursed at an amount which is 37% higher than that for female-specific surgeries. Recent increases in work RVUs for many gynecologic procedures have resulted in improved reimbursement. However, even with these improvements, significant gender bias still exists in the Medicare reimbursement of female-specific procedures. This gender bias is further magnified as more private insurance carriers use the system to set reimbursement.

  19. Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

    PubMed Central

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining the consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically-developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that

  20. Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment.

    PubMed

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D; Alm, Per; Jennische, Margareta; Bruce Tomblin, J; Ullman, Michael T

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these

  1. Molecular analysis of volatile metabolites released specifically by staphylococcus aureus and pseudomonas aeruginosa

    PubMed Central

    2012-01-01

    Background The routinely used microbiological diagnosis of ventilator associated pneumonia (VAP) is time consuming and often requires invasive methods for collection of human specimens (e.g. bronchoscopy). Therefore, it is of utmost interest to develop a non-invasive method for the early detection of bacterial infection in ventilated patients, preferably allowing the identification of the specific pathogens. The present work is an attempt to identify pathogen-derived volatile biomarkers in breath that can be used for early and non- invasive diagnosis of ventilator associated pneumonia (VAP). For this purpose, in vitro experiments with bacteria most frequently found in VAP patients, i.e. Staphylococcus aureus and Pseudomonas aeruginosa, were performed to investigate the release or consumption of volatile organic compounds (VOCs). Results Headspace samples were collected and preconcentrated on multibed sorption tubes at different time points and subsequently analyzed with gas chromatography mass spectrometry (GC-MS). As many as 32 and 37 volatile metabolites were released by S. aureus and P. aeruginosa, respectively. Distinct differences in the bacteria-specific VOC profiles were found, especially with regard to aldehydes (e.g. acetaldehyde, 3-methylbutanal), which were taken up only by P. aeruginosa but released by S. aureus. Differences in concentration profiles were also found for acids (e.g. isovaleric acid), ketones (e.g. acetoin, 2-nonanone), hydrocarbons (e.g. 2-butene, 1,10-undecadiene), alcohols (e.g. 2-methyl-1-propanol, 2-butanol), esters (e.g. ethyl formate, methyl 2-methylbutyrate), volatile sulfur compounds (VSCs, e.g. dimethylsulfide) and volatile nitrogen compounds (VNCs, e.g. 3-methylpyrrole). Importantly, a significant VOC release was found already 1.5 hours after culture start, corresponding to cell numbers of ~8*106 [CFUs/ml]. Conclusions The results obtained provide strong evidence that the detection and perhaps even identification of bacteria

  2. Mini-open blind procedure versus limited open technique for carpal tunnel release: a 30-month follow-up study.

    PubMed

    Cellocco, Paolo; Rossi, Constantino; Bizzarri, Francesco; Patrizio, Luigi; Costanzo, Giuseppe

    2005-05-01

    To evaluate prospectively the safety and effectiveness of a mini-open blind technique for carpal tunnel release (group A) when compared with a limited open technique (group B). From November 1999 to May 2001 (mean follow-up period, 30 mo) we performed 222 carpal tunnel release procedures on 185 consecutive patients. All patients were affected by mild to moderate median nerve compression. Patients in group A (82 patients, 99 procedures) had a short transverse incision at the wrist (length, 2 cm). We used a manual surgical instrument that helps in blindly dividing the flexor retinaculum because it has an integrated light source. The light makes it possible to locate precisely the tool blade by transillumination. Patients in group B (103 patients, 123 procedures) had a limited longitudinal incision (length, 3-4 cm). The preoperative and postoperative patient statuses were evaluated with an Italian modified version of the Boston Carpal Tunnel questionnaire with a mean of 30 months' follow-up after surgery (range, 24-39 mo). Group A patients showed better results than group B patients in all of the sections of the Italian modified version of the Boston Carpal Tunnel questionnaire at a mean follow-up period of 19 months, whereas after a mean of 30 months of follow-up evaluation the differences between groups A and B tended to decrease. Disease recurred in 7 group B patients, whereas only 1 patient in group A experienced symptom recurrence at the latest office evaluation. The blind mini-invasive technique has been shown to be as safe as traditional techniques but the recovery period is significantly shortened. With the technique we described a low recurrence rate was observed. All patients in group A reported great reduction in preoperative pain and numbness.

  3. Declarative and procedural memory in Danish speaking children with specific language impairment.

    PubMed

    Lum, Jarrad A G; Bleses, Dorthe

    2012-01-01

    It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge relatively unaffected. The current study examined memory and language functioning in 13 Danish-speaking children with SLI and 20 typically developing (TD) children. Participants were administered tasks assessing declarative, procedural and verbal working memory as well as knowledge of past tense and vocabulary. The SLI group performed significantly poorer than the TD group on the measure of verbal working memory. Non-significant differences between groups were observed on the measure of declarative memory, after controlling for verbal working memory. The groups were found to perform at comparable levels on the procedural memory task. On the language measures, the SLI group performed significantly poorer than the TD group on the past tense and vocabulary tasks. However, the magnitude of the difference was larger on the task assessing past tense. These results indicate grammatical knowledge is relatively more affected than lexical knowledge in Danish speaking children with SLI. However, the results were not consistent with the proposal linking impaired grammar to impairments with procedural memory. At the same time, the study does not rule out that other aspects of procedural learning and memory contribute to the language problems in SLI. The reader will be introduced to (1) different memory systems, in particular the declarative, procedural and working memory systems and (2) also research examining the relationship between these different memory systems and language in children with SLI. Copyright © 2011. Published by Elsevier Inc.

  4. Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release

    PubMed Central

    Chu, David S.H.; Johnson, Russell N.; Pun, Suzie H.

    2011-01-01

    Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK10, containing peptides composed of the linker phe-lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(l)-lysine for nucleic acid binding, (ii) pHCath(d)K10, containing the FKFL linker with oligo-(d)-lysine, and (iii) pH(d)Cath(d)K10, containing all (d) amino acids. Cathepsin B degraded copolymers pHCathK10 and pHCath(d)K10 within one hour while no degradation of pH(d)Cath(d)K10 was observed. Polyplexes formed with pHCathK10 copolymers show DNA release by 4 hrs of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(d)K10 and pH(d)Cath(d)K10 show no DNA release within 8 hrs. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK10 was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release. PMID:22036879

  5. A procedure for the analysis of site-specific and structure-specific fucosylation in alpha-1-antitrypsin

    PubMed Central

    Yin, Haidi; Zhu, Jianhui; Wu, Jing; Tan, Zhijing; An, Mingrui; Zhou, Shiyue; Mechref, Yehia; Lubman, David M.

    2016-01-01

    A MS-based methodology has been developed for analysis of core-fucosylated versus antennary-fucosylated glycosites in glycoproteins. This procedure is applied to the glycoprotein alpha-1-antitrypsin (A1AT), which contains both core- and antennary-fucosylated glycosites. The workflow involves digestion of intact glycoproteins into glycopeptides, followed by double digestion with sialidase and galactosidase. The resulting glycopeptides with truncated glycans were separated using an off-line HILIC (hydrophilic interaction liquid chromatography) separation where multiple fractions were collected at various time intervals. The glycopeptides in each fraction were treated with PNGase F and then divided into halves. One half of the sample was applied for peptide identification while the other half was processed for glycan analysis by derivatizing with a meladrazine reagent followed by MS analysis. This procedure provided site-specific identification of glycosylation sites and the ability to distinguish core fucosylation and antennary fucosylation via a double digestion and a mass profile scan. Both core and antennary fucosylation are shown to be present on various glycosites in A1AT. PMID:27439567

  6. Doxorubicin hydrochloride-oleic acid conjugate loaded nanostructured lipid carriers for tumor specific drug release.

    PubMed

    Zhao, Shuangni; Minh, Le Van; Li, Na; Garamus, Vasil M; Handge, Ulrich A; Liu, Jianwen; Zhang, Rongguang; Willumeit-Römer, Regine; Zou, Aihua

    2016-09-01

    The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment.

  7. Context-specific control in the single-prime negative-priming procedure.

    PubMed

    D'Angelo, Maria C; Milliken, Bruce

    2012-01-01

    The current paper examines the applicability of the context-specific control principle to the probe selection dependence of negative-priming effects using the single-prime procedure. In a series of experiments, we highlight the applicability of the context-specific control principle, first by illustrating a key result that implicates the role of context-specific control and challenges the contextual similarity principle. Following this, we show the importance of distinct probe contexts in the single-prime negative-priming procedure and report a novel finding that illustrates a learning effect that can occur within an experimental session. Finally, we test the relation of our novel learning effect to a related learning proposal offered by Frings and Wentura (2006), and we demonstrate that the learning involved in context-specific control is not dependent on contingency learning. Overall, the patterns of results highlight the role of context-sensitive memory in controlling how current perception and action are integrated with prior experience.

  8. Later learning stages in procedural memory are impaired in children with Specific Language Impairment.

    PubMed

    Desmottes, Lise; Meulemans, Thierry; Maillart, Christelle

    2016-01-01

    According to the Procedural Deficit Hypothesis (PDH), difficulties in the procedural memory system may contribute to the language difficulties encountered by children with Specific Language Impairment (SLI). Most studies investigating the PDH have used the sequence learning paradigm; however these studies have principally focused on initial sequence learning in a single practice session. The present study sought to extend these investigations by assessing the consolidation stage and longer-term retention of implicit sequence-specific knowledge in 42 children with or without SLI. Both groups of children completed a serial reaction time task and were tested 24h and one week after practice. Results showed that children with SLI succeeded as well as children with typical development (TD) in the early acquisition stage of the sequence learning task. However, as training blocks progressed, only TD children improved their sequence knowledge while children with SLI did not appear to evolve any more. Moreover, children with SLI showed a lack of the consolidation gains in sequence knowledge displayed by the TD children. Overall, these results were in line with the predictions of the PDH and suggest that later learning stages in procedural memory are impaired in SLI. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Improving the quality of procedure-specific operation reports in orthopaedic surgery

    PubMed Central

    Barritt, Andrew W; Clark, Laura; Cohen, Adam MM; Hosangadi-Jayedev, Naveen; Gibb, Paul A

    2010-01-01

    INTRODUCTION The objectives of this study were to: (i) assess whether handwritten operation reports for hip hemi-arthroplasties adhere to The Royal College of Surgeons of England (RCSE) guidelines on surgical documentation; (ii) improve adherence to these guidelines with procedure-specific computerised operation reports; and (iii) improve the quality of documentation in surgery. PATIENTS AND METHODS Thirty-three parameters based on RCSE guidelines were used to score hip hemi-arthroplasty operation reports. The first audit cycle was performed retrospectively to assess 50 handwritten operation reports, and the second cycle prospectively to assess 30 new computerised procedure-specific operation reports produced for hip hemi-arthroplasties. Eighty patients undergoing hip hemi-arthroplasty in a department of orthopaedic surgery within a UK hospital between September 2007 and August 2008 formed the study cohort. RESULTS The main outcome measure was the average scores attained by handwritten versus computerised operation reports. Handwritten reports scored an average of 58.7%, rising significantly (P < 0.01) to 92.8% following the introduction of detailed, computerised proformas for the operation note. Adherence to each RCSE parameter was improved. CONCLUSIONS Computerised proformas reduce variability between different operation reports for the same procedure and increase their content in line with RCSE recommendations. The proformas also constitute a more robust means of operative documentation. PMID:19995491

  10. A methodological, task-based approach to Procedure-Specific Simulations training.

    PubMed

    Setty, Yaki; Salzman, Oren

    2016-12-01

    Procedure-Specific Simulations (PSS) are 3D realistic simulations that provide a platform to practice complete surgical procedures in a virtual-reality environment. While PSS have the potential to improve surgeons' proficiency, there are no existing standards or guidelines for PSS development in a structured manner. We employ a unique platform inspired by game design to develop virtual reality simulations in three dimensions of urethrovesical anastomosis during radical prostatectomy. 3D visualization is supported by a stereo vision, providing a fully realistic view of the simulation. The software can be executed for any robotic surgery platform. Specifically, we tested the simulation under windows environment on the RobotiX Mentor. Using urethrovesical anastomosis during radical prostatectomy simulation as a representative example, we present a task-based methodological approach to PSS training. The methodology provides tasks in increasing levels of difficulty from a novice level of basic anatomy identification, to an expert level that permits testing new surgical approaches. The modular methodology presented here can be easily extended to support more complex tasks. We foresee this methodology as a tool used to integrate PSS as a complementary training process for surgical procedures.

  11. OBSERVATIONS ON THE RELEASE OF SERUM FIBRINOLYSIN BY SPECIFIC ANTIGEN, PEPTONE, AND CERTAIN POLYSACCHARIDES

    PubMed Central

    Ungar, Georges; Mist, Shirley H.

    1949-01-01

    Formation of fibrinolysin from its inactive precursor in serum was observed under the following conditions: (a) by adding the specific antigen to serum from sensitized guinea pigs; (b) by mixing normal guinea pig serum with peptone, agar, hyaluronic acid, chondroitinsulfuric acid, glycogen, pneumococcal polysaccharides, and heparin. Activation of profibrinolysin by these agents differs from chloroform or streptokinase activation in that it requires the presence of some serum constituent non-precipitable with the euglobulin fraction and destroyed by heating at 56°C. The bearing of these observations on the mechanism of anaphylactic and anaphylactoid reactions is discussed. The findings reported support the concept that proteolysis is part of the process determining the release of histamine and other toxic products. It is suggested that the presence of fibrinokinase may be responsible for the toxicity of serum induced in vitro by a number of agents. PMID:18152338

  12. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

    PubMed

    Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

    2017-08-22

    This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

  13. Reducing unnecessary preoperative blood orders and costs by implementing an updated institution-specific maximum surgical blood order schedule and a remote electronic blood release system.

    PubMed

    Frank, Steven M; Oleyar, Michael J; Ness, Paul M; Tobian, Aaron A R

    2014-09-01

    Using blood utilization data acquired from the anesthesia information management system, an updated institution-specific maximum surgical blood order schedule was introduced. The authors evaluated whether the maximum surgical blood order schedule, along with a remote electronic blood release system, reduced unnecessary preoperative blood orders and costs. At a large academic medical center, data for preoperative blood orders were analyzed for 63,916 surgical patients over a 34-month period. The new maximum surgical blood order schedule and the electronic blood release system (Hemosafe; Haemonetics Corp., Braintree, MA) were introduced mid-way through this time period. The authors assessed whether these interventions led to reductions in unnecessary preoperative orders and associated costs. Among patients having surgical procedures deemed not to require a type and screen or crossmatch (n = 33,216), the percent of procedures with preoperative blood orders decreased by 38% (from 40.4% [7,167 of 17,740 patients] to 25.0% [3,869 of 15,476 patients], P < 0.001). Among all hospitalized inpatients, the crossmatch-to-transfusion ratio decreased by 27% (from 2.11 to 1.54; P < 0.001) over the same time period. The proportion of patients who required emergency release uncrossmatched blood increased from 2.2 to 3.1 per 1,000 patients (P = 0.03); however, most of these patients were having emergency surgery. Based on the realized reductions in blood orders, annual costs were reduced by $137,223 ($6.08 per patient) for surgical patients, and by $298,966 ($6.20/patient) for all hospitalized patients. Implementing institution-specific, updated maximum surgical blood order schedule-directed preoperative blood ordering guidelines along with an electronic blood release system results in a substantial reduction in unnecessary orders and costs, with a clinically insignificant increase in requirement for emergency release blood transfusions.

  14. Population tailored modification of tuberculosis specific interferon-gamma release assay.

    PubMed

    Horvati, Kata; Bősze, Szilvia; Gideon, Hannah P; Bacsa, Bernadett; Szabó, Tamás G; Goliath, Rene; Rangaka, Molebogeng X; Hudecz, Ferenc; Wilkinson, Robert J; Wilkinson, Katalin A

    2016-02-01

    Blood-based Interferon-Gamma Release Assays (IGRA) identify Mycobacterium tuberculosis (MTB) sensitisation with increased specificity, but sensitivity remains impaired in human immunodeficiency virus (HIV) infected persons. The QuantiFERON-TB Gold In-Tube test contains peptide 38-55 of Rv2654c, based on data indicating differential recognition between tuberculosis patients and BCG vaccinated controls in Europe. We aimed to fine map the T cell response to Rv2654c with the view of improving sensitivity. Interferon-gamma ELISpot assay was used in HIV uninfected persons with latent and active tuberculosis to map peptide epitopes of Rv2654c. A modified IGRA was tested in two further groups of 55 HIV uninfected and 44 HIV infected persons, recruited in South Africa. The most prominently recognised peptide was between amino acids 51-65. Using p51-65 to boost the QuantiFERON-TB Gold In-Tube assay, the quantitative performance of the modified IGRA increased from 1.83 IU/ml (IQR 0.30-7.35) to 2.83 (IQR 0.28-12.2; p = 0.002) in the HIV uninfected group. In the HIV infected cohort the percentage of positive responders increased from 57% to 64% but only after 3 months of ART (p = ns). Our data shows the potential to population tailor detection of MTB sensitization using specific synthetic peptides and interferon-gamma release in vitro. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Degradation of tropoelastin by matrix metalloproteinases--cleavage site specificities and release of matrikines.

    PubMed

    Heinz, Andrea; Jung, Michael C; Duca, Laurent; Sippl, Wolfgang; Taddese, Samuel; Ihling, Christian; Rusciani, Anthony; Jahreis, Günther; Weiss, Anthony S; Neubert, Reinhard H H; Schmelzer, Christian E H

    2010-04-01

    To provide a basis for the development of approaches to treat elastin-degrading diseases, the aim of this study was to investigate the degradation of the natural substrate tropoelastin by the elastinolytic matrix metalloproteinases MMP-7, MMP-9, and MMP-12 and to compare the cleavage site specificities of the enzymes using complementary MS techniques and molecular modeling. Furthermore, the ability of the three proteases to release bioactive peptides was studied. Tropoelastin was readily degraded by all three MMPs. Eighty-nine cleavage sites in tropoelastin were identified for MMP-12, whereas MMP-7 and MMP-9 were found to cleave at only 58 and 63 sites, respectively. Cleavages occurred predominantly in the N-terminal and C-terminal regions of tropoelastin. With respect to the cleavage site specificities, the study revealed that all three MMPs similarly tolerate hydrophobic and/or aliphatic amino acids, including Pro, Gly, Ile, and Val, at P(1)'. MMP-7 shows a strong preference for Leu at P(1)', which is also well accepted by MMP-9 and MMP-12. Of all three MMPs, MMP-12 best tolerates bulky charged and aromatic amino acids at P(1)'. All three MMPs showed a clear preference for Pro at P(3) that could be structurally explained by molecular modeling. Analysis of the generated peptides revealed that all three MMPs show a similar ability to release bioactive sequences, with MMP-12 producing the highest number of these peptides. Furthermore, the generated peptides YTTGKLPYGYGPGG, YGARPGVGVGGIP, and PGFGAVPGA, containing GxxPG motifs that have not yet been proven to be bioactive, were identified as new matrikines upon biological activity testing.

  16. Fascial release effects on patients with non-specific cervical or lumbar pain.

    PubMed

    Tozzi, Paolo; Bongiorno, Davide; Vitturini, Claudio

    2011-10-01

    Myofascial Release (MFR) and Fascial Unwinding (FU) are widely used manual fascial techniques (MFTs), generally incorporated in treatment protocols to release fascial restrictions and restore tissue mobility. However, the effects of MFT on pain perception, and the mobility of fascial layers, have not previously been investigated using dynamic ultrasound (US) in patients with neck pain (NP) and low back pain (LBP). a) To show that US screening can be a useful tool to assess dysfunctional alteration of organ mobility in relation to their fascial layers, in people with non-specific NP or LBP, in the absence of any organ disease; b) To assess, by dynamic US screening, the change of sliding movements between superficial and deep fascia layers in the neck, in people with non-specific NP, before and after application of MFTs c) To assess, by dynamic US screening, the variation of right reno-diaphragmatic (RD) distance and of neck bladder (NB) mobility, in patients with non-specific LBP, before and after application of MFTs d) To evaluate 'if' and 'at what degree' pain perception may vary in patients with NP or LBP, after MFTs are applied, over the short term. An Experimental group of 60 subjects, 30 with non-specific NP and 30 with non-specific LBP, were assessed in the area of complaint, by Dynamic Ultrasound Topographic Anatomy Evaluation (D.US.T.A.-E.), before and after MFTs were applied in situ, in the corresponding painful region, for not more than 12 min. The results were compared with those from the respective Sham-Control group of 30 subjects. For the NP sub-groups, the pre- to post- US recorded videos of each subject were compared and assessed randomly and independently by two blinded experts in echographic screening. They were asked to rate the change observed in the cervical fascia sliding motions as 'none', 'discrete' or 'radical'. For the LBP sub-groups, a pre- to post- variation of the right RD distances and NB mobility were calculated on US imaging and

  17. Patient-specific atrium models for training and pre-procedure surgical planning

    NASA Astrophysics Data System (ADS)

    Laing, Justin; Moore, John; Bainbridge, Daniel; Drangova, Maria; Peters, Terry

    2017-03-01

    Minimally invasive cardiac procedures requiring a trans-septal puncture such as atrial ablation and MitraClip® mitral valve repair are becoming increasingly common. These procedures are performed on the beating heart, and require clinicians to rely on image-guided techniques. For cases of complex or diseased anatomy, in which fluoroscopic and echocardiography images can be difficult to interpret, clinicians may benefit from patient-specific atrial models that can be used for training, surgical planning, and the validation of new devices and guidance techniques. Computed tomography (CT) images of a patient's heart were segmented and used to generate geometric models to create a patient-specific atrial phantom. Using rapid prototyping, the geometric models were converted into physical representations and used to build a mold. The atria were then molded using tissue-mimicking materials and imaged using CT. The resulting images were segmented and used to generate a point cloud data set that could be registered to the original patient data. The absolute distance of the two point clouds was compared and evaluated to determine the model's accuracy. The result when comparing the molded model point cloud to the original data set, resulted in a maximum Euclidean distance error of 4.5 mm, an average error of 0.5 mm and a standard deviation of 0.6 mm. Using our workflow for creating atrial models, potential complications, particularly for complex repairs, may be accounted for in pre-operative planning. The information gained by clinicians involved in planning and performing the procedure should lead to shorter procedural times and better outcomes for patients.

  18. Specific disgust sensitivities differentially predict interest in careers of varying procedural-intensity among medical students.

    PubMed

    Consedine, Nathan S; Windsor, John A

    2014-05-01

    Mismatches between the needs of public health systems and student interests have led to renewed study on the factors predicting career specializations among medical students. While most work examines career and lifestyle values, emotional proclivities may be important; disgust sensitivity may help explain preferences for careers with greater and lesser degrees of procedural content. In the study, 294 students completed measures assessing: (1) demographics, (2) career interest or intention regarding emergency medicine, internal medicine, obstetrics/gynecology, and pediatric medicine, (3) traditional determinants of career intention/interest, and (4) core/bodily product, animal reminder, contamination, and sexual/moral disgust sensitivity. As predicted, logistic regressions controlling for demographics and traditional career predictors, showed that greater animal reminder disgust predicted reduced interest in emergency medicine but greater interest in pediatric medicine. Conversely, greater core/bodily product disgust predicted lower interest in obstetrics/gynecology and pediatric medicine; greater contamination and sexual/moral disgust both predicted increased odds of interest in internal medicine. Overall, specific disgust sensitivities were the best predictors of specialization intention in multivariate models. Specific disgust sensitivities appear to differentially deter and/or predispose self-selection into specific trajectories varying in procedural content. Such findings may permit the early identification of specialty fit and provide guidance in career counseling.

  19. Development and Validation of a Novel Robotic Procedure Specific Simulation Platform: Partial Nephrectomy.

    PubMed

    Hung, Andrew J; Shah, Swar H; Dalag, Leonard; Shin, Daniel; Gill, Inderbir S

    2015-08-01

    We developed a novel procedure specific simulation platform for robotic partial nephrectomy. In this study we prospectively evaluate its face, content, construct and concurrent validity. This hybrid platform features augmented reality and virtual reality. Augmented reality involves 3-dimensional robotic partial nephrectomy surgical videos overlaid with virtual instruments to teach surgical anatomy, technical skills and operative steps. Advanced technical skills are assessed with an embedded full virtual reality renorrhaphy task. Participants were classified as novice (no surgical training, 15), intermediate (less than 100 robotic cases, 13) or expert (100 or more robotic cases, 14) and prospectively assessed. Cohort performance was compared with the Kruskal-Wallis test (construct validity). Post-study questionnaire was used to assess the realism of simulation (face validity) and usefulness for training (content validity). Concurrent validity evaluated correlation between virtual reality renorrhaphy task and a live porcine robotic partial nephrectomy performance (Spearman's analysis). Experts rated the augmented reality content as realistic (median 8/10) and helpful for resident/fellow training (8.0-8.2/10). Experts rated the platform highly for teaching anatomy (9/10) and operative steps (8.5/10) but moderately for technical skills (7.5/10). Experts and intermediates outperformed novices (construct validity) in efficiency (p=0.0002) and accuracy (p=0.002). For virtual reality renorrhaphy, experts outperformed intermediates on GEARS metrics (p=0.002). Virtual reality renorrhaphy and in vivo porcine robotic partial nephrectomy performance correlated significantly (r=0.8, p <0.0001) (concurrent validity). This augmented reality simulation platform displayed face, content and construct validity. Performance in the procedure specific virtual reality task correlated highly with a porcine model (concurrent validity). Future efforts will integrate procedure specific

  20. Specific immunotherapy with mugwort pollen allergoid reduce bradykinin release into the nasal fluid

    PubMed Central

    Grzanka, Alicja; Jawor, Barbara; Czecior, Eugeniusz

    2016-01-01

    Introduction A pathomechanism of allergic rhinitis is complex. A neurogenic mechanism seems to play a significant role in this phenomenon. Aim The evaluation of influence of specific immunotherapy of mugwort pollen allergic patients on the bradykinin concentration in the nasal lavage fluid. Material and methods The study included 22 seasonal allergic rhinitis patients. Thirty persons with monovalent allergy to mugwort pollen, confirmed with skin prick tests and allergen-specific immunoglobulin E, underwent a 3-year-long allergen immunotherapy with the mugwort extract (Allergovit, Allergopharma, Germany). The control group was composed of 9 persons with polyvalent sensitivity to pollen, who were treated with pharmacotherapy. Before the allergen-specific immunotherapy (AIT) and in subsequent years before the pollen seasons, a provocation allergen test with the mugwort extract was performed, together with collection of nasal fluids, where bradykinin concentration was determined according to Proud method. Results There were similar levels of bradykinin in both groups at baseline prior to therapy (AIT group: 584.0 ±87.2 vs. controls 606.3 ±106.5 pg/ml) and changes after allergen challenge 1112.4 ±334.8 vs. 1013.3 ±305.9 pg/ml as well. The bradykinin concentration in nasal lavage fluid after mugwort challenge in 1 year was lower in the AIT group (824.1 ±184.2 pg/ml vs. 1000.4 ±411.5 pg/l; p < 005) with a further significant decrease after the 2nd and 3rd year of specific immunotherapy. Significant reduction of symptoms and medications use was observed in hyposensitized patients. Conclusions A decreased level of bradykinin as a result of AIT suggests that some of the symptomatic benefits of AIT may be related to the reduced release of bradykinin into nasal secretions. These values correlate with clinical improvement within the course of treatment. PMID:27605897

  1. Specific involvement of gonadal hormones in the functional maturation of growth hormone releasing hormone (GHRH) neurons.

    PubMed

    Gouty-Colomer, Laurie-Anne; Méry, Pierre-François; Storme, Emilie; Gavois, Elodie; Robinson, Iain C; Guérineau, Nathalie C; Mollard, Patrice; Desarménien, Michel G

    2010-12-01

    Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.

  2. New procedure for isolation of Rous sarcoma virus-specific RNA from infected cells.

    PubMed Central

    Bromley, P A; Spahr, P F; Darlix, J L

    1979-01-01

    The use of mercurated "strong stop" complementary DNA (complementary to the 5'-terminal 101 nucleotides of Rous sarcoma virus RNA) in the isolation of virus-specific RNA from infected chicken embryo fibroblasts is described. Strong stop Rous sarcoma virus complementary DNA was mercurated chemically, and, as a result of the low complexity of this DNA, short hybridization times (up to 15 min) and heating in the absence of formamide were found to be adequate conditions for the isolation of virus-specific RNA. The purity of the isolated RNA was demonstrated by analysis of labeled RNase T1-resistant oligonucleotides by two-dimensional polyacrylamide gel electrophoresis. The isolated RNA could be translated in the in vitro protein synthesis system derived from rabbit reticulocytes, and an analysis of polypeptides programmed by isolated RNA before and after immunoprecipitation further demonstrated both the purity of the isolated mRNA and the quantitative nature of the isolation procedure. Images PMID:228062

  3. Individual-specific transgenerational marking of fish populations based on a barium dual-isotope procedure.

    PubMed

    Huelga-Suarez, Gonzalo; Moldovan, Mariella; Garcia-Valiente, America; Garcia-Vazquez, Eva; Alonso, J Ignacio Garcia

    2012-01-03

    The present study focuses on the development and evaluation of an individual-specific transgenerational marking procedure using two enriched barium isotopes, (135)Ba and (137)Ba, mixed at a given and selectable molar ratio. The method is based on the deconvolution of the isotope patterns found in the sample into four molar contribution factors: natural xenon (Xe nat), natural barium (Ba nat), Ba135, and Ba137. The ratio of molar contributions between Ba137 and Ba135 is constant and independent of the contribution of natural barium in the sample. This procedure was tested in brown trout ( Salmo trutta ) kept in captivity. Trout were injected with three different Ba137/Ba135 isotopic signatures ca. 7 months and 7 days before spawning to compare the efficiency of the marking procedure at long and short term, respectively. The barium isotopic profiles were measured in the offspring by means of inductively coupled plasma mass spectrometry. Each of the three different isotopic signatures was unequivocally identified in the offspring in both whole eggs and larvae. For 9 month old offspring, the characteristic barium isotope signatures could also be detected in the otoliths even in the presence of a high and variable amount of barium of natural isotope abundance. In conclusion, it can be stated that the proposed dual-isotope marking is inheritable and can be detected after both long-term and short-term marking. Furthermore, the dual-isotope marking can be made individual-specific, so that it allows identification of offspring from a single individual or a group of individuals within a given fish group.

  4. RE-PERG, a new procedure for electrophysiologic diagnosis of glaucoma that may improve PERG specificity

    PubMed Central

    Mavilio, Alberto; Sisto, Dario; Ferreri, Paolo; Cardascia, Nicola; Alessio, Giovanni

    2017-01-01

    Purpose A significant variability of the second harmonic (2ndH) phase of steady-state pattern electroretinogram (SS-PERG) in intrasession retest has been recently described in glaucoma patients (GP), which has not been found in healthy subjects. To evaluate the reliability of phase variability in retest (a procedure called RE-PERG or REPERG) in the presence of cataract, which is known to affect standard PERG, we tested this procedure in GP, normal controls (NC), and cataract patients (CP). Methods The procedure was performed on 50 GP, 35 NC, and 27 CP. All subjects were examined with RE-PERG and SS-PERG and also with spectral domain optical coherence tomography and standard automated perimetry. Standard deviation of phase and amplitude value of 2ndH were correlated by means of one-way analysis of variance and Pearson correlation, with the mean deviation and pattern standard deviation assessed by standard automated perimetry and retinal nerve fiber layer and the ganglion cell complex thickness assessed by spectral domain optical coherence tomography. Receiver operating characteristics were calculated in cohort populations with and without cataract. Results Standard deviation of phase of 2ndH was significantly higher in GP with respect to NC (P<0.001) and CP (P<0.001), and it correlated with retinal nerve fiber layer (r=−0.5, P<0.001) and ganglion cell complex (r=−0.6, P<0.001) defects in GP. Receiver operating characteristic evaluation showed higher specificity of RE-PERG (86.4%; area under the curve 0.93) with respect to SS-PERG (54.5%; area under the curve 0.68) in CP. Conclusion RE-PERG may improve the specificity of SS-PERG in clinical practice in the discrimination of GP. PMID:28176965

  5. Density functional theory simulations of polyethylene: principal Hugoniot, specific heats, compression and release isentropes

    NASA Astrophysics Data System (ADS)

    Cochrane, K. R.; Desjarlais, M. P.; Mattsson, T. R.

    2011-06-01

    An accurate equation of state (EOS) for polyethylene is required in order to model high energy density experiments for CH2 densities above 1 g/cc, temperatures above 1 eV, and pressures above 1 Mbar. Density Functional Theory (DFT) based molecular dynamics has been established as a method capable of yielding high fidelity results for many materials at a wide range of pressures and temperatures and has recently been applied to complex polymers such as polyethylene. Using high density polyethylene as the reference state, we compute the principal Hugoniot to 350 GPa, compression isentrope, and several release isentropes from states on the principal Hugoniot. We also calculate the specific heat and the dissociation along the Hugoniot. Our simulation results are validated by comparing to experimental data and then used to construct a wide range EOS. Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corp., a subsidiary of Lockheed Martin Corp., for the U.S. Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000.

  6. Evaluation of a sustained-release oral tetracycline in non-specific urethritis.

    PubMed Central

    Perera, P M

    1975-01-01

    A double-blind trial of oxytetracycline (Imperacin-I.C.I.) and tetracycline hydrochloride in a sustained-release formulation (Tetrabid-Organon) was carried out on 259 men suffering from non-specific urethritis. Patients who had NSU in the preceeding 3 months were excluded from the trial. The response to treatment assessed at 10 days was favourable in ninety patients out of 129 (35 per cent.) who received oxytetracycline and in 89 patients out of 130 (34 per cent.) who received Tetrabid-Organon. Eight patients in each group required re-treatment and the remainder failed to attend for follow-up. At 4 weeks after treatment one (1-3 per cent.) of 74 patients treated with Tetrabid-Organon and twenty (37-7 per cent.) of patients treated with oxytetracycline required further treatment. A large proportion of patients who were free of signs and symptoms at the first follow-up failed to return at 4 weeks, so that the true rates of cure at 4 weeks are difficult to assess. In a field such as venereology, the twice-daily administration of medication offers distinct advantages over a four-times-daily regime. This study suggests that Tetrabid-Organon, a tetracycline designed specifically for twice-daily dosage, is more effective than standard oxytetracycline, given twice daily, in the treatment of NSU. It was satisfying to find that the traditional advice concerning abstention from sexual activity and alcohol consumption during the treatment of NSU has a sound basis. The study showed a close correlation between recurrence of NSU and failure to follow such advice. It would be interesting to investigate the means by which alcohol consumption may act to delay recovery. PMID:1104076

  7. Corticotropin-releasing hormone activates ERK1/2 MAPK in specific brain areas.

    PubMed

    Refojo, Damián; Echenique, Carlos; Müller, Marianne B; Reul, Johannes M H M; Deussing, Jan M; Wurst, Wolfgang; Sillaber, Inge; Paez-Pereda, Marcelo; Holsboer, Florian; Arzt, Eduardo

    2005-04-26

    Corticotropin-releasing hormone (CRH) coordinates hormonal and behavioral responses to stress. The mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2) mediates several functions in different forebrain structures and recently has been implicated in CRH signaling in cultured cells. To study in vivo CRH-mediated activation of central ERK1/2, we investigated the expression pattern of the phosphorylated ERK1/2(p-ERK1/2) in the mouse brain after intracerebroventricular CRH injections. As shown by immunohistochemistry and confocal microscopy analysis, CRH administration increased p-ERK1/2 levels specifically in the CA3 and CA1 hippocampal subfields and basolateral complex of the amygdala, both structures related to external environmental information processing and behavioral aspects of stress. Other regions such as hypothalamic nuclei and the central nucleus of the amygdala, also related to central CRH system but involved in the processing of the ascending visceral information and neuroendocrine-autonomic response to stress, did not show CRH-mediated ERK1/2 activation. To dissect the involvement of CRH receptor 1 (CRHR1) and CRHR2, we used conditional knockout mice in which Crhr1 is inactivated in the anterior forebrain and limbic structures. The conditional genetic ablation of Crhr1 inhibited the p-ERK1/2 increase, underlining the involvement of CRHR1 in the CRH-mediated activation. These findings underscore the fact that CRH activates p-ERK1/2 through CRHR1 only in selected brain regions, pointing to a specific role of this pathway in mediating behavioral adaptation to stress.

  8. Specific CD4+ T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis.

    PubMed

    Volz, Magdalena Sarah; Moos, Verena; Allers, Kristina; Luge, Enno; Mayer-Scholl, Anne; Nöckler, Karsten; Loddenkemper, Christoph; Jansen, Andreas; Schneider, Thomas

    2015-12-01

    Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4(+) T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4(+) T cells. The production of inflammatory cytokines such as TNF-α by CD4(+) T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease.

  9. Specific CD4+ T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

    PubMed Central

    Moos, Verena; Allers, Kristina; Luge, Enno; Mayer-Scholl, Anne; Nöckler, Karsten; Loddenkemper, Christoph; Jansen, Andreas; Schneider, Thomas

    2015-01-01

    Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4+ T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4+ T cells. The production of inflammatory cytokines such as TNF-α by CD4+ T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease. PMID:26491036

  10. GIS-based procedure for site-specific risk assessment of pesticides for aquatic ecosystems.

    PubMed

    Sala, Serenella; Vighi, Marco

    2008-01-01

    The EU Water Framework Directive states that the management of surface water must be based on a site-specific assessment of water quality, that is dependent on land use. As a result, to develop a robust chemical management policy for aquatic ecosystems, the ecotoxicological risk must be strictly related to the local conditions and characteristics of the system. This paper presents a methodology developed to assess the ecotoxicological risk of pesticides to site-specific aquatic ecosystems. Spatial and relational databases, provisional models and risk indices were integrated into Geographical Information Systems (GIS) to produce maps of exposure, effect and risk at watershed scale. Each active ingredient is characterised by a data set that includes input data as well as results represented by a risk assessment cartography. The aim of this procedure is to perform a site-specific risk assessment by integrating geographical distribution of predicted environmental concentrations (PECs), ecotoxicological effects and the potential/actual quality of the exposed ecosystem. Examples of pesticide risk maps for surface waters in Lombardia Region (Northern Italy) are shown.

  11. Specific low temperature release of 131Xe from irradiated MOX fuel

    NASA Astrophysics Data System (ADS)

    Hiernaut, J.-P.; Wiss, T.; Rondinella, V. V.; Colle, J.-Y.; Sasahara, A.; Sonoda, T.; Konings, R. J. M.

    2009-08-01

    A particular low temperature behaviour of the 131Xe isotope was observed during release studies of fission gases from MOX fuel samples irradiated at 44.5 GWd/tHM. A reproducible release peak, representing 2.7% of the total release of the only 131Xe, was observed at ˜1000 K, the rest of the release curve being essentially identical for all the other xenon isotopes. The integral isotopic composition of the different xenon isotopes is in very good agreement with the inventory calculated using ORIGEN-2. The presence of this particular release is explained by the relation between the thermal diffusion and decay properties of the various iodine radioisotopes decaying all into xenon.

  12. Procedure of recovery of pin-by-pin fields of energy release in the core of VVER-type reactor for the BIPR-8 code

    SciTech Connect

    Gordienko, P. V. Kotsarev, A. V.; Lizorkin, M. P.

    2014-12-15

    The procedure of recovery of pin-by-pin energy-release fields for the BIPR-8 code and the algorithm of the BIPR-8 code which is used in nodal computation of the reactor core and on which the recovery of pin-by-pin fields of energy release is based are briefly described. The description and results of the verification using the module of recovery of pin-by-pin energy-release fields and the TVS-M program are given.

  13. DNA intercalators induce specific release of HMG 14, HMG 17 and other DNA-binding proteins from chicken erythrocyte chromatin.

    PubMed Central

    Schröter, H; Maier, G; Ponstingl, H; Nordheim, A

    1985-01-01

    Chicken erythrocyte nuclei were incubated with DNA intercalating agents in order to isolate from chromatin specific DNA-binding proteins whose binding specificity may be determined by DNA secondary and/or tertiary structure. The intercalating agents ethidium bromide (EtBr) and propidium iodide induce the specific release of high mobility group proteins HMG 14 and HMG 17 under low ionic strength conditions. Chloroquine (CQ) intercalation also results in the selective liberation of HMG 14 and HMG 17, but, in addition, selectively releases other nuclear proteins (including histone H1A) in a pH- and ionic strength-dependent fashion. The use of this new 'elutive intercalation' technique for the isolation and purification of 'sequence-specific' and 'helix-specific' DNA-binding proteins is suggested. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. PMID:4092697

  14. Synaptic vesicle pool-specific modification of neurotransmitter release by intravesicular free radical generation.

    PubMed

    Afuwape, Olusoji A T; Wasser, Catherine R; Schikorski, Thomas; Kavalali, Ege T

    2017-02-15

    Synaptic transmission is mediated by the release of neurotransmitters from synaptic vesicles in response to stimulation or through the spontaneous fusion of a synaptic vesicle with the presynaptic plasma membrane. There is growing evidence that synaptic vesicles undergoing spontaneous fusion versus those fusing in response to stimuli are functionally distinct. In this study, we acutely probe the effects of intravesicular free radical generation on synaptic vesicles that fuse spontaneously or in response to stimuli. By targeting vesicles that preferentially release spontaneously, we can dissociate the effects of intravesicular free radical generation on spontaneous neurotransmission from evoked neurotransmission and vice versa. Taken together, these results further advance our knowledge of the synapse and the nature of the different synaptic vesicle pools mediating neurotransmission. Earlier studies suggest that spontaneous and evoked neurotransmitter release processes are maintained by synaptic vesicles which are segregated into functionally distinct pools. However, direct interrogation of the link between this putative synaptic vesicle pool heterogeneity and neurotransmission has been difficult. To examine this link, we tagged vesicles with horseradish peroxidase (HRP) - a haem-containing plant enzyme - or antibodies against synaptotagmin-1 (syt1). Filling recycling vesicles in hippocampal neurons with HRP and subsequent treatment with hydrogen peroxide (H2 O2 ) modified the properties of neurotransmitter release depending on the route of HRP uptake. While strong depolarization-induced uptake of HRP suppressed evoked release and augmented spontaneous release, HRP uptake during mild activity selectively impaired evoked release, whereas HRP uptake at rest solely potentiated spontaneous release. Expression of a luminal HRP-tagged syt1 construct and subsequent H2 O2 application resulted in a similar increase in spontaneous release and suppression as well as

  15. Functional specificity of amino acid at position 246 in the tRNA mimicry domain of bacterial release factor 2.

    PubMed

    Uno, M; Ito, K; Nakamura, Y

    1996-01-01

    The termination of protein synthesis in bacteria requires codon-specific polypeptide release factors RF-1 (UAG/UAA specific) and RF-2 (UGA/UAA specific). We have proposed that release factors mimic tRNA and recognize the stop codon for polypeptide release (Nakamura et al (1996) Cell 87, 147-150). In contrast to the textbook view, genetic experiments have indicated that Escherichia coli RF-2 terminates translation very weakly at UAA while Salmonella RF-2 decodes this signal efficiently. Moreover, an excess of E coli RF-2 was toxic to cells while an excess of Salmonella RF-2 was not. These two RF-2 proteins are identical except for 16 out of 365 amino acids. Fragment swap experiments and site-directed mutagenesis revealed that a residue at position 246 is solely responsible for these two phenotypes. Upon substituting Ala (equivalent to Salmonella RF-2) for Thr-246 of E coli RF-2, the protein acquired increased release activity for UAA as well as for UGA. These results led us to conclude that E coli RF-2 activity is potentially weak and that the amino acid at position 246 plays a crucial role, not for codon discrimination, but for stop codon recognition or polypeptide release, presumably constituting an essential moiety of tRNA mimicry or interacting with peptidyltransferase centers of the ribosome.

  16. Light-stimulated cargo release from a core–shell structured nanocomposite for site-specific delivery

    SciTech Connect

    Cai, Yun; Ling, Li; Li, Xiaofang; Chen, Meng; Su, Likai

    2015-03-15

    This paper reported a core–shell structured site-specific delivery system with a light switch triggered by low energy light (λ=510 nm). Its core was composed of supermagnetic Fe{sub 3}O{sub 4} nanoparticles for magnetic guiding and targeting. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for cargo capacity. A light switch N1-(4aH-cyclopenta[1,2-b:5,4-b′]dipyridin-5(5aH)-ylidene)benzene-1, 4-diamine (CBD) was covalently grafted into these hexagonal tunnels, serving as light stimuli acceptor with loading content of 1.1 μM/g. This composite was fully characterized and confirmed by SEM, TEM, XRD patterns, N{sub 2} adsorption/desorption, thermogravimetric analysis, IR, UV–vis absorption and emission spectra. Experimental data suggested that this composite had a core as wide as 150 nm and could be magnetically guided to specific sites. Its hexagonal tunnels were as long as 180 nm. Upon light stimuli of “on” and “off” states, controllable release was observed with short release time of ~900 s (90% capacity). - Graphical abstract: A core–shell structured site-specific delivery system with a light switch triggered by yellow light was constructed. Controllable release was observed with short release time of ~900 s (90% capacity). - Highlights: • A core–shell structured site-specific delivery system was constructed. • It consisted of Fe{sub 3}O{sub 4} core and MCM-41 shell grafted with light switch. • This delivery system was triggered by low energy light. • Controllable release was observed with short release time of ~900 s.

  17. A Monte Carlo procedure for the construction of complementary cumulative distribution functions for comparison with the EPA release limits for radioactive waste disposal

    SciTech Connect

    Helton, J.C.; Shiver, A.W.

    1994-10-01

    A Monte Carlo procedure for the construction of complementary cumulative distribution functions (CCDFs) for comparison with the US Environmental Protection Agency (EPA) release limits for radioactive waste disposal (40 CFR 191, Subpart B) is described and illustrated with results from a recent performance assessment (PA) for the Waste Isolation Pilot Plant (WIPP). The Monte Carlo procedure produces CCDF estimates similar to those obtained with stratified sampling in several recent PAs for the WIPP. The advantages of the Monte Carlo procedure over stratified sampling include increased resolution in the calculation of probabilities for complex scenarios involving drilling intrusions and better use of the necessarily limited number of mechanistic calculations that underlie CCDF construction.

  18. Reduced overnight consolidation of procedural learning in chronic medicated schizophrenia is related to specific sleep stages.

    PubMed

    Manoach, Dara S; Thakkar, Katharine N; Stroynowski, Eva; Ely, Alice; McKinley, Sophia K; Wamsley, Erin; Djonlagic, Ina; Vangel, Mark G; Goff, Donald C; Stickgold, Robert

    2010-01-01

    We previously reported that patients with schizophrenia failed to demonstrate normal sleep-dependent improvement in motor procedural learning. Here, we tested whether this failure was associated with the duration of Stage 2 sleep in the last quartile of the night (S2q4) and with spindle activity during this epoch. Fourteen patients with schizophrenia and 15 demographically matched controls performed a motor sequence task (MST) before and after a night of polysomnographically monitored sleep. Patients showed no significant overnight task improvement and significantly less than controls, who did show significant improvement. While there were no group differences in overall sleep architecture, patients showed significant reductions in fast sigma frequency power (45%) and in spindle density (43%) during S2q4 sleep at the electrode proximal to the motor cortex controlling the hand that performed the MST. Although spindle activity did not correlate with overnight improvement in either group, S2q4 sleep duration in patients significantly correlated with the plateau level of overnight improvement seen at the end of the morning testing session, and slow wave sleep (SWS) duration correlated with the delay in reaching this plateau. SWS and S2q4 sleep each predicted the initial level of overnight improvement in schizophrenia, and their product explained 77% of the variance, suggesting that both sleep stages are necessary for consolidation. These findings replicate our prior observation of reduced sleep-dependent consolidation of motor procedural learning in schizophrenia and link this deficit to specific sleep stages. They provide further evidence that sleep is an important contributor to cognitive deficits in schizophrenia.

  19. A systematic model specification procedure for an illness-death model without recovery.

    PubMed

    Eulenburg, Christine; Mahner, Sven; Woelber, Linn; Wegscheider, Karl

    2015-01-01

    Multi-state models are a flexible tool for analyzing complex time-to-event problems with multiple endpoints. Compared to the Cox regression model with a single endpoint or a summarizing composite endpoint, they can provide a more detailed insight into the disease process. Furthermore, prognosis can be improved by including information from intermediate events occurring during the course of the disease. Different model variants, options and additional assumptions provide many possibilities, but at the same time complicate the implementation of multi-state techniques. So far, no guiding literature is available to specify a multi-state model systematically. The objective of this work was to set up a general specification procedure for an illness-death model that optimizes the model fit and predictive accuracy by stepwise reduction of the model. As an application example, we reanalyzed data from an observational study of 434 ovarian cancer patients with progression as intermediate and death as absorbing state. The technique is described in general terms and can be applied to other illness-death models without recovery. The clock-reset approach was used, implicating that the time was reset to zero after progression. The non-homogeneous semi-Markov characteristic stated that the present time as well as the time between surgery and progression influenced survival after progression. Covariate effects on transitions were estimated and proportionality of transition baseline hazards was tested. The finally developed model optimized the accuracy of predictions for two simulated patients. This stepwise procedure yields parsimonious but targeted multi-state models with well interpretable coefficients and optimized predictive ability, even for smaller data sets.

  20. 40 CFR 63.7521 - What fuel analyses, fuel specification, and procedures must I use?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... composite fuel samples for each fuel type according to the procedures in paragraph (c)(1) or (2) of this... subpart. Gaseous and liquid fuels are exempt from the sampling requirements in paragraphs (c) and (d) of... procedures to be used for collecting and preparing the composite samples if your procedures are...

  1. Tunable Controlled Release of Bioactive SDF-1α via Protein Specific Interactions within Fibrin/Nanoparticle Composites.

    PubMed

    Dutta, D; Fauer, C; Mulleneux, H L; Stabenfeldt, S E

    2015-10-31

    The chemokine, stromal cell-derived factor 1α (SDF-1α), is a key regulator of the endogenous neural progenitor/stem cell-mediated regenerative response after neural injury. Increased and sustained bioavailability of SDF-1α in the peri-injury region is hypothesized to modulate this endogenous repair response. Here, we describe poly(lactic-co-glycolic) acid (PLGA) nanoparticles capable of releasing bioactive SDF-1α in a sustained manner over 60days after a burst of 23%. Moreover, we report a biphasic cellular response to SDF-1α concentrations thus the large initial burst release in an in vivo setting may result in supratherapeutic concentrations of SDF-1α. Specific protein-protein interactions between SDF-1α and fibrin (as well as its monomer, fibrinogen) were exploited to control the magnitude of the burst release. Nanoparticles embedded in fibrin significantly reduced the amount of SDF-1α released after 72 hrs as a function of fibrin density. Therefore, the nanoparticle/fibrin composites represented a means to independently tune the magnitude of the burst phase release from the nanoparticles while perserving a bioactive depot of SDF-1α for release over 60days.

  2. Tunable Controlled Release of Bioactive SDF-1α via Protein Specific Interactions within Fibrin/Nanoparticle Composites

    PubMed Central

    Dutta, D.; Fauer, C.; Mulleneux, H.L.; Stabenfeldt, S. E.

    2015-01-01

    The chemokine, stromal cell-derived factor 1α (SDF-1α), is a key regulator of the endogenous neural progenitor/stem cell-mediated regenerative response after neural injury. Increased and sustained bioavailability of SDF-1α in the peri-injury region is hypothesized to modulate this endogenous repair response. Here, we describe poly(lactic-co-glycolic) acid (PLGA) nanoparticles capable of releasing bioactive SDF-1α in a sustained manner over 60days after a burst of 23%. Moreover, we report a biphasic cellular response to SDF-1α concentrations thus the large initial burst release in an in vivo setting may result in supratherapeutic concentrations of SDF-1α. Specific protein-protein interactions between SDF-1α and fibrin (as well as its monomer, fibrinogen) were exploited to control the magnitude of the burst release. Nanoparticles embedded in fibrin significantly reduced the amount of SDF-1α released after 72 hrs as a function of fibrin density. Therefore, the nanoparticle/fibrin composites represented a means to independently tune the magnitude of the burst phase release from the nanoparticles while perserving a bioactive depot of SDF-1α for release over 60days. PMID:26660666

  3. Fatty acyl specificity of the receptor-mediated release of polyunsaturated fatty acids from vascular endothelial cells

    SciTech Connect

    Rosenthal, M.D.

    1987-05-01

    Histamine and bradykinin appear to exhibit the same fatty acid specificity as thrombin. Incubation of human umbilical vein endothelial cells with 10 ..mu..M histamine for 10 min in buffered saline containing 50 ..mu..M fat-free albumin stimulates the release of previously incorporated (/sup 14/C)arachidonate but not (/sup 14/C)22:4(n-6) or (/sup 14/C)20:3(n-6). Similarly calf pulmonary artery endothelial cells release (/sup 14/C)arachidonate but not (/sup 14/C)22:4(n-6) in response to either bradykinin (1 /sup +/g/ml) or histamine (10..mu..M). In both types of endothelial cells, the calcium ionophore A23187 (10 ..mu..M) exhibits the same pattern of fatty acyl specificity as the receptor-mediated agonists. By contrast, mellitin (2-4 ..mu..g/ml) stimulates the release of free 22:4(n-6) and oleate in addition to arachidonate; release of 22:4(n-6) is 30-70% that of arachidonate. These results suggest that histamine, bradykinin and thrombin stimulate a common calcium-dependent fatty acyl-specific phospholipase activity.

  4. 50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... refuge-specific hunting regulations? 32.3 Section 32.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM HUNTING AND FISHING General Provisions § 32.3 What are the procedures for publication of refuge-specific hunting...

  5. 50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... refuge-specific hunting regulations? 32.3 Section 32.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM HUNTING AND FISHING General Provisions § 32.3 What are the procedures for publication of refuge-specific hunting...

  6. 50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... refuge-specific hunting regulations? 32.3 Section 32.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM HUNTING AND FISHING General Provisions § 32.3 What are the procedures for publication of refuge-specific hunting...

  7. Surgical Site Infection following Cesarean Delivery: Patient, Provider, and Procedure-Specific Risk Factors.

    PubMed

    Shree, Raj; Park, Seo Young; Beigi, Richard H; Dunn, Shannon L; Krans, Elizabeth E

    2016-01-01

    This study aims to identify risk factors for cesarean delivery (CD) surgical site infection (SSI). study design: Retrospective analysis of 2,739 CDs performed at the University of Pittsburgh in 2011. CD SSIs were defined using National Healthcare Safety Network (NHSN) criteria. Chi-square test and t-test were used for bivariate analyses and multivariate logistic regression was used to identify SSI risk factors. Of 2,739 CDs, 178 (6.5%) were complicated by SSI. Patients with a SSI were more likely to have Medicaid, have resident physicians perform the CD, an American Society of Anesthesiologists (ASA) class of ≥ 3, chorioamnionitis, tobacco use, and labor before CD. In multivariable analysis, labor (odds ratio [OR], 2.35; 95% confidence interval [95% CI], 1.65-3.38), chorioamnionitis (OR, 2.24; 95% CI, 1.25-3.83), resident teaching service (OR, 2.15; 95% CI, 1.54-3.00), tobacco use (OR, 1.70; 95% CI, 1.04-2.70), ASA class ≥ 3 (OR, 1.61; 95% CI, 1.06-2.39), and CDs performed for nonreassuring fetal status (OR, 0.43; 95% CI, 0.26-0.67) were significantly associated with CD SSI. Multiple patient, provider, and procedure-specific risk factors contribute to CD SSI risk which may be targeted in infection-control efforts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. An augmented reality system for patient-specific guidance of cardiac catheter ablation procedures.

    PubMed

    De Buck, Stijn; Maes, Frederik; Ector, Joris; Bogaert, Jan; Dymarkowski, Steven; Heidbüchel, Hein; Suetens, Paul

    2005-11-01

    We present a system to assist in the treatment of cardiac arrhythmias by catheter ablation. A patient-specific three-dimensional (3-D) anatomical model, constructed from magnetic resonance images, is merged with fluoroscopic images in an augmented reality environment that enables the transfer of electrocardiography (ECG) measurements and cardiac activation times onto the model. Accurate mapping is realized through the combination of: a new calibration technique, adapted to catheter guided treatments; a visual matching registration technique, allowing the electrophysiologist to align the model with contrast-enhanced images; and the use of virtual catheters, which enable the annotation of multiple ECG measurements on the model. These annotations can be visualized by color coding on the patient model. We provide an accuracy analysis of each of these components independently. Based on simulation and experiments, we determined a segmentation error of 0.6 mm, a calibration error in the order of 1 mm and a target registration error of 1.04 +/- 0.45 mm. The system provides a 3-D visualization of the cardiac activation pattern which may facilitate and improve diagnosis and treatment of the arrhytmia. Because of its low cost and similar advantages we believe our approach can compete with existing commercial solutions, which rely on dedicated hardware and costly catheters. We provide qualitative results of the first clinical use of the system in 11 ablation procedures.

  9. Surgical site infection following cesarean delivery: patient, provider and procedure specific risk factors

    PubMed Central

    SHREE, Raj; Park, Seo Young; Beigi, Richard H.; Dunn, Shannon L.; Krans, Elizabeth E.

    2016-01-01

    Objective To identify risk factors for cesarean delivery (CD) surgical site infection (SSI). Study Design Retrospective analysis of 2739 CDs performed at the University of Pittsburgh in 2011. CD SSI’s were defined using National Healthcare Safety Network (NHSN) criteria. Chi-square and t tests were used for bivariate analyses and multivariate logistic regression was used to identify SSI risk factors. Results Of 2739 CDs, 178 (6.5%) were complicated by SSI. Patients with a SSI were more likely to have Medicaid, have resident physicians perform the CD, an ASA class of ≥3, chorioamnionitis, use tobacco and labor prior to CD. In multivariable analysis, labor (2.35;1.65–3.38), chorioamnionitis (2.24;1.25–3.83), resident teaching service (2.15;1.54–3.00), tobacco use (1.70; 1.04–2.70), ASA class ≥3 (1.61; 1.06–2.39) and CDs performed for non-reassuring fetal status (0.43; 0.26–0.67) were significantly associated with CD SSI. Conclusion Multiple patient, provider and procedure specific-risk factors contribute to CD SSI risk which may be targeted in infection control efforts. PMID:26344010

  10. Time-specific contribution of the supplementary motor area to intermanual transfer of procedural knowledge

    PubMed Central

    Perez, MA; Tanaka, S; Wise, SP; Willingham, DT; Cohen, LG

    2008-01-01

    The supplementary motor area (SMA) makes a crucial contribution to intermanual transfer: the ability to use one hand to perform a skill practiced and learned with the other hand. However, the timing of this contribution relative to movement remains unknown. Here, 33 healthy volunteers performed a 12-item sequence in the serial reaction time task (SRTT). During training, each participant responded to a sequence of visual cues presented at 1 Hz by pressing one of 4 keys with their right hand. The measure of intermanual transfer was response time (RT) during repetition of the trained sequence with the left hand, which was at rest during learning. Participants were divided into 3 groups, which did not differ in their learning rates or amounts. In 2 groups, 1 Hz repetitive transcranial magnetic stimulation (rTMS) induced transient virtual lesions of the SMA during training, either 100 ms before each cue (the premovement group) or during each key press (the movement group). The third group received sham stimulation (the sham group). After training with the right hand, RTs for performance with the left (transfer) hand were longer for the premovement group than for the movement or sham groups. Thus SMA’s most crucial contribution to intermanual transfer occurs in the interval between movements, when the memory of a prior movement plays a role in encoding specific sequences. These results provide insight into frontal-lobe contributions to procedural knowledge. PMID:18815252

  11. The angiosome concept in clinical practice: implications for patient-specific recanalization procedures.

    PubMed

    Brodmann, M

    2013-10-01

    Below-the-knee (BTK) disease with the clinical presentation of critical limb ischemia is associated with a high rate of limb loss due to minor and major amputations. The main problem is to find a way to optimize blood flow to the critical limb area. BTK joint the down-stream diverges into 3 arms which supply different areas. Different concepts exist how optimal blood flow to the critical ischemic areas BTK can be achieved, either by treating as many vessels as can be reopened by an endovascular procedure, or by going for the two main BTK vessels, or in an outstanding situation also to treat the inflow of collaterals to achieve as much blood flow down the foot as possible. Derived from plastic surgery for the purpose of healing of flaps, the angiosome concept has been developed. An angiosome is an anatomic unit of tissue (consisting of skin, subcutaneous tissue, fascia, muscle and bone) fed by a source artery and drained by specific veins. From that point of view it can be presumed that revascularization of the source artery to the angiosome might result in better wound healing and limb salvage rates. The angiosome treatment concept of BTK disease refers to the concept in cardiology, where discrimination of reversible ischemia areas is made and respective vessels leading to these areas are treated in a distinctive way.

  12. A sensitive and specific assay for superoxide anion released by neutrophils or macrophages based on bioluminescence of polynoidin.

    PubMed

    Colepicolo, P; Camarero, V C; Nicolas, M T; Bassot, J M; Karnovsky, M L; Hastings, J W

    1990-02-01

    Using the luminescent protein polynoidin, present in the bioluminescent system isolated from the marine annelid Harmothoe lunulata, we have developed a new method to measure, specifically, superoxide anion (O2-) released by macrophages or neutrophils. A small quantity of an aqueous crude extract of polynoidin is used to detect O2- released by stimulated cells. Light emission is linearly dependent on the number of cells over a wide range (10(3) to 10(7) cells), and the assay is thus more sensitive than either luminol or ferricytochrome c reduction. Luminescence is enhanced 20% by mannitol, 80% by catalase, and is totally quenched by superoxide dismutase. For the same number of cells, neutrophils showed a threefold higher release of O2- and a twofold faster first-order light decay than stimulated macrophages, in accordance with data obtained by other methods.

  13. PREVENTION REFERENCE MANUAL: CHEMICAL SPECIFIC, VOLUME 14: CONTROL OF ACCIDENTAL RELEASES OF PHOSGENE

    EPA Science Inventory

    The report, discussing phosgene, is one of a series addressing the prevention of accidental releases of toxic chemicals. Phosgene, a highly reactive and corrosive liquid that boils at room temperature has an Immediately Dangerous to Life and Health (lDLH) conctntration of 2 ppm, ...

  14. PREVENTION REFERENCE MANUAL: CHEMICAL SPECIFIC. VOL. 15: CONTROL OF ACCIDENTAL RELEASES OF SULFUR TRIOXIDE

    EPA Science Inventory

    The report, discussing sulfur trioxide (SO3), is one of a series addressing the prevention of accidental releases of toxic chemicals. SO3, a clear oily liquid or solid at typical ambient conditions, has an Immediately Dangerous to Life and Health (IDLH) concentration of 20 ppm, w...

  15. Establishing patient-specific criteria for selecting the optimal upper extremity vascular access procedure

    PubMed Central

    Woo, Karen; Ulloa, Jesus; Allon, Michael; Carsten, Christopher G.; Chemla, Eric S.; Henry, Mitchell L.; Huber, Thomas S.; Lawson, Jeffrey H.; Lok, Charmaine E.; Peden, Eric K.; Scher, Larry; Sidawy, Anton; Maggard-Gibbons, Melinda; Cull, David

    2017-01-01

    Objective The Kidney Disease Outcome Quality Initiative and Fistula First Breakthrough Initiative call for the indiscriminate creation of arteriovenous fistulas (AVFs) over arteriovenous grafts (AVGs) without providing patient-specific criteria for vascular access selection. Although the U.S. AVF rate has increased dramatically, several reports have found that this singular focus on increasing AVFs has resulted in increased AVF nonmaturation/early failure and a high prevalence of catheter dependence. The objective of this study was to determine the appropriateness of vascular access procedures in clinical scenarios constructed with combinations of relevant factors potentially influencing outcomes. Methods The RAND/UCLA Appropriateness Method was used. Accordingly, a comprehensive literature search was performed and a synthesis of results compiled. The RAND/UCLA Appropriateness Method was applied to 2088 AVF and 1728 AVG clinical scenarios with varying patient characteristics. Eleven international vascular access experts rated the appropriateness of each scenario in two rounds. On the basis of the distribution of the panelists’ scores, each scenario was determined to be appropriate, inappropriate, or indeterminate. Results Panelists achieved agreement in 2964 (77.7%) scenarios; 860 (41%) AVF and 588 (34%) AVG scenarios were scored appropriate, 686 (33%) AVF and 480 (28%) AVG scenarios were scored inappropriate, and 542 (26%) AVF and 660 (38%) AVG scenarios were indeterminate. Younger age, larger outflow vein diameter, normal or obese body mass index (vs morbidly obese), larger inflow artery diameter, and higher patient functional status were associated with appropriateness of AVF creation. Older age, dialysis dependence, and smaller vein size were associated with appropriateness of AVG creation. Gender, diabetes, and coronary artery disease were not associated with AVF or AVG appropriateness. Dialysis status was not associated with AVF appropriateness. Body mass

  16. Target-specific regulation of presynaptic release properties at auditory nerve terminals in the avian cochlear nucleus

    PubMed Central

    Ahn, J.

    2015-01-01

    Short-term synaptic plasticity (STP) acts as a time- and firing rate-dependent filter that mediates the transmission of information across synapses. In the auditory brain stem, the divergent pathways that encode acoustic timing and intensity information express differential STP. To investigate what factors determine the plasticity expressed at different terminals, we tested whether presynaptic release probability differed in the auditory nerve projections to the two divisions of the avian cochlear nucleus, nucleus angularis (NA) and nucleus magnocellularis (NM). Estimates of release probability were made with an open-channel blocker of N-methyl-d-aspartate (NMDA) receptors. Activity-dependent blockade of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) with application of 20 μM (+)-MK801 maleate was more rapid in NM than in NA, indicating that release probability was significantly higher at terminals in NM. Paired-pulse ratio (PPR) was tightly correlated with the blockade rate at terminals in NA, suggesting that PPR was a reasonable proxy for relative release probability at these synapses. To test whether release probability was similar across convergent inputs onto NA neurons, PPRs of different nerve inputs onto the same postsynaptic NA target neuron were measured. The PPRs, as well as the plasticity during short trains, were tightly correlated across multiple inputs, further suggesting that release probability is coordinated at auditory nerve terminals in a target-specific manner. This highly specific regulation of STP in the auditory brain stem provides evidence that the synaptic dynamics are tuned to differentially transmit the auditory information in nerve activity into parallel ascending pathways. PMID:26719087

  17. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines.

    PubMed

    Filho, Edismauro Garcia Freitas; da Silva, Elaine Zayas Marcelino; Zanotto, Camila Ziliotto; Oliver, Constance; Jamur, Maria Célia

    2016-01-01

    Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.

  18. Provision of specific dental procedures by general dentists in the National Dental Practice-Based Research Network: questionnaire findings.

    PubMed

    Gilbert, Gregg H; Gordan, Valeria V; Korelitz, James J; Fellows, Jeffrey L; Meyerowitz, Cyril; Oates, Thomas W; Rindal, D Brad; Gregory, Randall J

    2015-01-22

    Objectives were to: (1) determine whether and how often general dentists (GDs) provide specific dental procedures; and (2) test the hypothesis that provision is associated with key dentist, practice, and patient characteristics. GDs (n = 2,367) in the United States National Dental Practice-Based Research Network completed an Enrollment Questionnaire that included: (1) dentist; (2) practice; and (3) patient characteristics, and how commonly they provide each of 10 dental procedures. We determined how commonly procedures were provided and tested the hypothesis that provision was substantively related to the three sets of characteristics. Two procedure categories were classified as "uncommon" (orthodontics, periodontal surgery), three were "common" (molar endodontics; implants; non-surgical periodontics), and five were "very common" (restorative; esthetic procedures; extractions; removable prosthetics; non-molar endodontics). Dentist, practice, and patient characteristics were substantively related to procedure provision; several characteristics seemed to have pervasive effects, such as dentist gender, training after dental school, full-time/part-time status, private practice vs. institutional practice, presence of a specialist in the same practice, and insurance status of patients. As a group, GDs provide a comprehensive range of procedures. However, provision by individual dentists is substantively related to certain dentist, practice, and patient characteristics. A large number and broad range of factors seem to influence which procedures GDs provide. This may have implications for how GDs respond to the ever-changing landscape of dental care utilization, patient population demography, scope of practice, delivery models and GDs' evolving role in primary care.

  19. Arsenic release from Fe/Mn oxide-rich (model) soils/sediments - A comparison of single extraction procedures

    NASA Astrophysics Data System (ADS)

    Vanek, A.; Komarek, M.; Galuskova, I.

    2012-04-01

    Arsenic extractability in As-modified Fe(III) and Mn(III,IV) oxide-coated sands was tested using five widely used 2-h single extraction procedures: deionised water, 0.01 M CaCl2, 1 M NH4NO3, 0.1 M Na2HPO4 and 0.005 DTPA. In general, the highest As recoveries reaching 39-50% of total As concentration were observed for all extracting media in the birnessite (delta-MnO2) system, indicating relatively weak adsorption of As onto the Mn oxides. The Na2HPO4 extracts from the Fe oxide systems (i.e., associated with ferrihydrite and goethite) were highest in As, accounting for up to 34% of total As amount. Surprisingly, comparable recoveries of As (14-20%) yielded deionised water, CaCl2, NH4NO3, DTPA as extracting media for both ferrihydrite and goethite coatings. Deionised water and Na2HPO4 extractions are suggested for quick estimation of easily soluble, exchangeable and/or specifically adsorbed As in real soil/sediment samples.

  20. Operator competence in fetoscopic laser surgery for twin-twin transfusion syndrome: validation of a procedure-specific evaluation tool.

    PubMed

    Peeters, S H P; Akkermans, J; Bustraan, J; Middeldorp, J M; Lopriore, E; Devlieger, R; Lewi, L; Deprest, J; Oepkes, D

    2016-03-01

    Fetoscopic laser surgery for twin-twin transfusion syndrome is a procedure for which no objective tools exist to assess technical skills. To ensure that future fetal surgeons reach competence prior to performing the procedure unsupervised, we developed a performance assessment tool. The aim of this study was to validate this assessment tool for reliability and construct validity. We made use of a procedure-specific evaluation instrument containing all essential steps of the fetoscopic laser procedure, which was previously created using Delphi methodology. Eleven experts and 13 novices from three fetal medicine centers performed the procedure on the same simulator. Two independent observers assessed each surgery using the instrument (maximum score: 52). Interobserver reliability was assessed using Spearman correlation. We compared the performance of novices and experts to assess construct validity. The interobserver reliability was high (Rs  = 0.974, P < 0.001). Checklist scores for experts and novices were significantly different; the median score for novices was 28/52 (54%), whereas that for experts was 47.5/52 (91%) (P < 0.001). The procedure time and fetoscopy time were significantly shorter (P < 0.001) for experts. Residual anastomoses were found in 1/11 (9%) procedures performed by experts and in 9/13 (69%) procedures performed by novices (P = 0.005). Multivariable analysis showed that the checklist score, independent of age and gender, predicted competence. The procedure-specific assessment tool for fetoscopic laser surgery shows good interobserver reliability and discriminates experts from novices. This instrument may therefore be a useful tool in the training curriculum for fetal surgeons. Further intervention studies with reassessment before and after training may increase the construct validity of the tool. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  1. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons.

    PubMed

    Katona, I; Sperlágh, B; Sík, A; Käfalvi, A; Vizi, E S; Mackie, K; Freund, T F

    1999-06-01

    To understand the functional significance and mechanisms of action in the CNS of endogenous and exogenous cannabinoids, it is crucial to identify the neural elements that serve as the structural substrate of these actions. We used a recently developed antibody against the CB1 cannabinoid receptor to study this question in hippocampal networks. Interneurons with features typical of basket cells showed a selective, intense staining for CB1 in all hippocampal subfields and layers. Most of them (85.6%) contained cholecystokinin (CCK), which corresponded to 96.9% of all CCK-positive interneurons, whereas only 4.6% of the parvalbumin (PV)-containing basket cells expressed CB1. Accordingly, electron microscopy revealed that CB1-immunoreactive axon terminals of CCK-containing basket cells surrounded the somata and proximal dendrites of pyramidal neurons, whereas PV-positive basket cell terminals in similar locations were negative for CB1. The synthetic cannabinoid agonist WIN 55,212-2 (0.01-3 microM) reduced dose-dependently the electrical field stimulation-induced [3H]GABA release from superfused hippocampal slices, with an EC50 value of 0. 041 microM. Inhibition of GABA release by WIN 55,212-2 was not mediated by inhibition of glutamatergic transmission because the WIN 55,212-2 effect was not reduced by the glutamate blockers AP5 and CNQX. In contrast, the CB1 cannabinoid receptor antagonist SR 141716A (1 microM) prevented this effect, whereas by itself it did not change the outflow of [3H]GABA. These results suggest that cannabinoid-mediated modulation of hippocampal interneuron networks operate largely via presynaptic receptors on CCK-immunoreactive basket cell terminals. Reduction of GABA release from these terminals is the likely mechanism by which both endogenous and exogenous CB1 ligands interfere with hippocampal network oscillations and associated cognitive functions.

  2. Definition of Specific Functions and Procedural Skills Required by Cuban Specialists in Intensive Care and Emergency Medicine.

    PubMed

    Véliz, Pedro L; Berra, Esperanza M; Jorna, Ana R

    2015-07-01

    INTRODUCTION Medical specialties' core curricula should take into account functions to be carried out, positions to be filled and populations to be served. The functions in the professional profile for specialty training of Cuban intensive care and emergency medicine specialists do not include all the activities that they actually perform in professional practice. OBJECTIVE Define the specific functions and procedural skills required of Cuban specialists in intensive care and emergency medicine. METHODS The study was conducted from April 2011 to September 2013. A three-stage methodological strategy was designed using qualitative techniques. By purposive maximum variation sampling, 82 professionals were selected. Documentary analysis and key informant criteria were used in the first stage. Two expert groups were formed in the second stage: one used various group techniques (focus group, oral and written brainstorming) and the second used a three-round Delphi method. In the final stage, a third group of experts was questioned in semistructured in-depth interviews, and a two-round Delphi method was employed to assess priorities. RESULTS Ultimately, 78 specific functions were defined: 47 (60.3%) patient care, 16 (20.5%) managerial, 6 (7.7%) teaching, and 9 (11.5%) research. Thirty-one procedural skills were identified. The specific functions and procedural skills defined relate to the profession's requirements in clinical care of the critically ill, management of patient services, teaching and research at the specialist's different occupational levels. CONCLUSIONS The specific functions and procedural skills required of intensive care and emergency medicine specialists were precisely identified by a scientific method. This product is key to improving the quality of teaching, research, administration and patient care in this specialty in Cuba. The specific functions and procedural skills identified are theoretical, practical, methodological and social contributions to

  3. Introduction to Psychology and Leadership. Design Specifications Document Including Specifications for Product and Course Design System Management and Evaluation Procedures.

    ERIC Educational Resources Information Center

    Westinghouse Learning Corp., Annapolis, MD.

    The design specifications for the United States Naval Academy leadership course developed by Westinghouse Learning Corporation are presented in this report, covering course system design, management, and evaluation. EM 010 418 through EM 010 447 and EM 010 451 through EM 010 512 are related documents, with the final report appearing under EM 010…

  4. Specific features of sensorimotor cerebral cortex activity modulation by dopamine releaser amantadine.

    PubMed

    Storozhuk, Viktor M; Zinyuk, Larissa E

    2007-09-01

    The modulatory effects of amantadine (1-adamantanamine) on the activity of sensorimotor cerebral cortex neurones during microiontophoretic application of agonists of glutamatergic and GABA-ergic (gamma-aminobutyric acid) transmission were studied. In non-anaesthetised cats, dopamine (DA) released by amantadine application in a small area of the neocortex increased baseline and evoked neuronal activity, providing stabilization and optimum course of both the neuronal and the conditioned responses of the animal. Amantadine eliminates a decrease in the level of neuronal baseline and evoked activity and marked increase in the latency of neuronal activation and conditioned movement mediated by D2 receptor antagonist sulpiride ((S)-5-aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-methoamantadineybenzamide) or GABA. This is reflected by a proportionate decrease in the onset of neuronal impulse reaction and latency of conditioned movement. Combined NMDA (N-methyl-D: -aspartate) and amantadine application also caused a considerable increase in baseline and evoked activity, but produced a slightly weaker effect than that evoked by NMDA application alone. A decrease in the baseline and evoked neuronal activity after NMDA withdrawn lasted during next control session (up to 40 min). The ability of DA releaser amantadine to alleviate significant increase in the latency of neuronal responses and conditioned movement induced by sulpiride or GABA suggests that dopamine modulates the activity of GABA-ergic inhibitory fast spike interneurons in the cat sensorimotor cortex during conditioning.

  5. Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells.

    PubMed

    de Girolamo, L; Stanco, D; Galliera, E; Viganò, M; Colombini, A; Setti, S; Vianello, E; Corsi Romanelli, M M; Sansone, V

    2013-07-01

    Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells (TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs' proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model.

  6. Target cell-specific modulation of transmitter release at terminals from a single axon.

    PubMed

    Scanziani, M; Gähwiler, B H; Charpak, S

    1998-09-29

    In the hippocampus, a CA3 pyramidal cell forms excitatory synapses with thousands of other pyramidal cells and inhibitory interneurons. By using sequential paired recordings from three connected cells, we show that the presynaptic properties of CA3 pyramidal cell terminals, belonging to the same axon, differ according to the type of target cell. Activation of presynaptic group III metabotropic glutamate receptors decreases transmitter release only at terminals contacting CA1 interneurons but not CA1 pyramidal cells. Furthermore, terminals contacting distinct target cells show different frequency facilitation. On the basis of these results, we conclude that the pharmacological and physiological properties of presynaptic terminals are determined, at least in part, by the target cells.

  7. Target Cell-Specific Modulation of Transmitter Release at Terminals from a Single Axon

    NASA Astrophysics Data System (ADS)

    Scanziani, Massimo; Gahwiler, Beat H.; Charpak, Serge

    1998-09-01

    In the hippocampus, a CA3 pyramidal cell forms excitatory synapses with thousands of other pyramidal cells and inhibitory interneurons. By using sequential paired recordings from three connected cells, we show that the presynaptic properties of CA3 pyramidal cell terminals, belonging to the same axon, differ according to the type of target cell. Activation of presynaptic group III metabotropic glutamate receptors decreases transmitter release only at terminals contacting CA1 interneurons but not CA1 pyramidal cells. Furthermore, terminals contacting distinct target cells show different frequency facilitation. On the basis of these results, we conclude that the pharmacological and physiological properties of presynaptic terminals are determined, at least in part, by the target cells.

  8. Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

    PubMed

    Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

    2017-09-09

    In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

  9. Understanding calcium homeostasis in postnatal gonadotropin-releasing hormone neurons using cell-specific Pericam transgenics.

    PubMed

    Constantin, Stéphanie; Jasoni, Christine; Romanò, Nicola; Lee, Kiho; Herbison, Allan E

    2012-01-01

    The gonadotropin-releasing hormone (GnRH) neurons are the key output cells of a complex neuronal network controlling fertility in mammals. To examine calcium homeostasis in postnatal GnRH neurons, we generated a transgenic mouse line in which the genetically encodable calcium indicator ratiometric Pericam (rPericam) was targeted to the GnRH neurons. This mouse model enabled real-time imaging of calcium concentrations in GnRH neurons in the acute brain slice preparation. Investigations in GnRH-rPericam mice revealed that GnRH neurons exhibited spontaneous, long-duration (~8s) calcium transients. Dual electrical-calcium recordings revealed that the calcium transients were correlated perfectly with burst firing in GnRH neurons and that calcium transients in GnRH neurons regulated two calcium-activated potassium channels that, in turn, determined burst firing dynamics in these cells. Curiously, the occurrence of calcium transients in GnRH neurons across puberty or through the estrous cycle did not correlate well with the assumption that GnRH neuron burst firing was contributory to changing patterns of pulsatile GnRH release at these times. The GnRH-rPericam mouse was also valuable in determining differential mechanisms of GABA and glutamate control of calcium levels in GnRH neurons as well as effects of G-protein-coupled receptors for GnRH and kisspeptin. The simultaneous measurement of calcium levels in multiple GnRH neurons was hampered by variable rPericam fluorescence in different GnRH neurons. Nevertheless, in the multiple recordings that were achieved no evidence was found for synchronous calcium transients. Together, these observations show the great utility of transgenic targeting strategies for investigating the roles of calcium with specified neuronal cell types. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Interfaces for knowledge-base builders control knowledge and application-specific procedures

    SciTech Connect

    Hirsch, P.; Katke, W.; Meier, M.; Snyder, S.; Stillman, R.

    1986-01-01

    Expert System Environment/VM is an expert system shell-a general-purpose system for constructing and executing expert system applications. An application expert has both factual knowledge about an application and knowledge about how that factual knowledge should be organized and processed. In addition, many applications require application-dependent procedures to access databases or to do specialized processing. An important and novel part of Expert System Environment/VM is the technique used to allow the expert or knowledge-base builder to enter the control knowledge and to interface with application-dependent procedures. This paper discusses these high-level interfaces for the knowledge-base builder.

  11. Effects of Muscle-Specific Oxidative Stress on Cytochrome c Release and Oxidation-Reduction Potential Properties.

    PubMed

    Ke, Yiling; Mitacek, Rachel M; Abraham, Anupam; Mafi, Gretchen G; VanOverbeke, Deborah L; DeSilva, Udaya; Ramanathan, Ranjith

    2017-09-06

    Mitochondria play a significant role in beef color. However, the role of oxidative stress in cytochrome c release and mitochondrial degradation is not clear. The objective was to determine the effects of display time on cytochrome c content and oxidation-reduction potential (ORP) of beef longissimus lumborum (LL) and psoas major (PM) muscles. PM discolored by day 3 compared with LL. On day 0, mitochondrial content and mitochondrial oxygen consumption were greater in PM than LL. However, mitochondrial content and oxygen consumption were lower (P < 0.05) in PM than LL by day 7. Conversely, cytochrome c content in sarcoplasm was greater on days 3 and 7 for PM than LL. There were no significant differences in ORP for LL during display, but ORP increased for PM on day 3 when compared with day 0. The results suggest that muscle-specific oxidative stress can affect cytochrome c release and ORP changes.

  12. A Monte Carlo procedure for the construction of complementary cumulative distribution functions for comparison with the EPA release limits for radioactive waste disposal.

    PubMed

    Helton, J C; Shiver, A W

    1996-02-01

    A Monte Carlo procedure for the construction of complementary cumulative distribution functions (CCDFs) for comparison with the U.S. Environmental Protection Agency (EPA) release limits for radioactive waste disposal (40 CFR 191, Subpart B) is described and illustrated with results from a recent performance assessment (PA) for the Waste Isolation Pilot Plant (WIPP). The Monte Carlo procedure produces CCDF estimates similar to those obtained with importance sampling in several recent PAs for the WIPP. The advantages of the Monte Carlo procedure over importance sampling include increased resolution in the calculation of probabilities for complex scenarios involving drilling intrusions and better use of the necessarily limited number of mechanistic calculations that underlie CCDF construction.

  13. 24 CFR 200.937 - Supplementary specific procedural requirements under HUD building product standards and...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... requirements under HUD building product standards and certification program for plastic bathtub units, plastic shower receptors and stalls, plastic lavatories, plastic water closet bowls and tanks. 200.937 Section... procedural requirements under HUD building product standards and certification program for plastic bathtub...

  14. 24 CFR 200.937 - Supplementary specific procedural requirements under HUD building product standards and...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... requirements under HUD building product standards and certification program for plastic bathtub units, plastic shower receptors and stalls, plastic lavatories, plastic water closet bowls and tanks. 200.937 Section... procedural requirements under HUD building product standards and certification program for plastic bathtub...

  15. 24 CFR 200.937 - Supplementary specific procedural requirements under HUD building product standards and...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... requirements under HUD building product standards and certification program for plastic bathtub units, plastic shower receptors and stalls, plastic lavatories, plastic water closet bowls and tanks. 200.937 Section... procedural requirements under HUD building product standards and certification program for plastic bathtub...

  16. 24 CFR 200.937 - Supplementary specific procedural requirements under HUD building product standards and...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements under HUD building product standards and certification program for plastic bathtub units, plastic shower receptors and stalls, plastic lavatories, plastic water closet bowls and tanks. 200.937 Section... procedural requirements under HUD building product standards and certification program for plastic bathtub...

  17. 50 CFR 648.90 - NE multispecies assessment, framework procedures and specifications, and flexible area action...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...; survey results; stock status; current estimates of fishing mortality and overfishing levels; social and... that may result in overfishing for a particular stock. Any adjustments to the ACLs in year two will be... projects in the EEZ. This procedure may also be used to modify FMP overfishing definitions and...

  18. 50 CFR 648.90 - NE multispecies assessment, framework procedures and specifications, and flexible area action...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...; survey results; stock status; current estimates of fishing mortality and overfishing levels; social and... that may result in overfishing for a particular stock. Any adjustments to the ACLs in year two will be... of aquaculture projects in the EEZ. This procedure may also be used to modify FMP...

  19. VERIFICATION OF SIMPLIFIED PROCEDURES FOR SITE- SPECIFIC SO2 AND NOX CONTROL COST ESTIMATES

    EPA Science Inventory

    The report documents results of an evaluation to verify the accuracy of simplified procedures for estimating sulfur dioxide (S02) and nitrogen oxides (NOx) retrofit control costs and performance for 200 502-emitting coal-fired power plants in the 31-state eastern region. nitially...

  20. VERIFICATION OF SIMPLIFIED PROCEDURES FOR SITE- SPECIFIC SO2 AND NOX CONTROL COST ESTIMATES

    EPA Science Inventory

    The report documents results of an evaluation to verify the accuracy of simplified procedures for estimating sulfur dioxide (S02) and nitrogen oxides (NOx) retrofit control costs and performance for 200 502-emitting coal-fired power plants in the 31-state eastern region. nitially...

  1. 40 CFR Appendix A to Part 75 - Specifications and Test Procedures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... require) performing a flow profile study following the procedures in 40 CFR part 60, appendix A, method, 1... equal to 1/2 duct diameter upstream from a flow disturbance. If a flow profile study shows that cyclonic... flow profile study, if performed, are acceptable (i.e., there are no cyclonic (or swirling) or...

  2. The effects of timing of exposure to principles and procedural instruction specificity on learning an electrical troubleshooting skill.

    PubMed

    Eiriksdottir, Elsa; Catrambone, Richard

    2015-12-01

    Domain principles provided in task instructions are assumed to help performance as learners can later apply this knowledge when faced with new tasks. The goal of the research was to investigate whether the timing of the exposure to principles-studying the principles before or while completing training tasks-and the specificity in the accompanying step-by-step procedural instructions would influence learning to troubleshoot a simulated electrical circuit. The results of a pilot study suggested that timing of principle exposure and specificity might interact. This was investigated by comparing the performance of 4 groups of participants (n = 24) who received either general or detailed procedural instructions and were either exposed to the principles before or during the training. The results showed that studying the principles before training benefited test task performance when the procedural instructions were detailed but not when they were general. The results also showed that using general procedural instructions benefited test task performance while using detailed procedural instructions benefited training task performance. Overall the results reveal how the learning situation as a whole must be considered when determining the efficacy of instructional materials, and how conditions can be created where principles enhance learning. (c) 2015 APA, all rights reserved).

  3. Effects of superovulation with oFSH and norgestomet/GnRH-controlled release of the LH surge on hormone concentrations, and yield of oocytes and embryos at specific developmental stages.

    PubMed

    Knijn, H M; Fokker, W; van der Weijden, G C; Dieleman, S J; Vos, P L A M

    2012-04-01

    The objective of this study was to evaluate a new superovulation procedure with oFSH after temporary suppression of the endogenous LH surge by norgestomet followed by administration of GnRH, to collect bovine oocytes and embryos at specific developmental stages. Since 1999, our research group applies this superovulation procedure with controlled release of the endogenous LH surge. The objective of this study is to verify if this procedure is reliable for collection of oocytes and embryos at specific time points of development and if it produces a sufficient number of both oocytes and embryos of good quality. This procedure was validated regarding to hormonal characteristics, superovulatory response and both oocyte and embryo yield at different times of in vivo development. The results demonstrate that the procedure used to control the occurrence of the pre-ovulatory LH surge was effective in 92% of the animals (n = 238) and even in 99% of the animals the oocytes and embryos were collected at the intended stage of development. The superovulatory response and both oocyte, embryo yield and quality were similar to the average yield in Europe reported by Association Européenne de transfert embryonnaire (AETE). In conclusion, this superovulation procedure provides a valid tool to collect oocytes and embryos at specific time points of development. © 2008 Blackwell Verlag GmbH.

  4. A scalable architecture for incremental specification and maintenance of procedural and declarative clinical decision-support knowledge.

    PubMed

    Hatsek, Avner; Shahar, Yuval; Taieb-Maimon, Meirav; Shalom, Erez; Klimov, Denis; Lunenfeld, Eitan

    2010-01-01

    Clinical guidelines have been shown to improve the quality of medical care and to reduce its costs. However, most guidelines exist in a free-text representation and, without automation, are not sufficiently accessible to clinicians at the point of care. A prerequisite for automated guideline application is a machine-comprehensible representation of the guidelines. In this study, we designed and implemented a scalable architecture to support medical experts and knowledge engineers in specifying and maintaining the procedural and declarative aspects of clinical guideline knowledge, resulting in a machine comprehensible representation. The new framework significantly extends our previous work on the Digital electronic Guidelines Library (DeGeL) The current study designed and implemented a graphical framework for specification of declarative and procedural clinical knowledge, Gesher. We performed three different experiments to evaluate the functionality and usability of the major aspects of the new framework: Specification of procedural clinical knowledge, specification of declarative clinical knowledge, and exploration of a given clinical guideline. The subjects included clinicians and knowledge engineers (overall, 27 participants). The evaluations indicated high levels of completeness and correctness of the guideline specification process by both the clinicians and the knowledge engineers, although the best results, in the case of declarative-knowledge specification, were achieved by teams including a clinician and a knowledge engineer. The usability scores were high as well, although the clinicians' assessment was significantly lower than the assessment of the knowledge engineers.

  5. A Scalable Architecture for Incremental Specification and Maintenance of Procedural and Declarative Clinical Decision-Support Knowledge

    PubMed Central

    Hatsek, Avner; Shahar, Yuval; Taieb-Maimon, Meirav; Shalom, Erez; Klimov, Denis; Lunenfeld, Eitan

    2010-01-01

    Clinical guidelines have been shown to improve the quality of medical care and to reduce its costs. However, most guidelines exist in a free-text representation and, without automation, are not sufficiently accessible to clinicians at the point of care. A prerequisite for automated guideline application is a machine-comprehensible representation of the guidelines. In this study, we designed and implemented a scalable architecture to support medical experts and knowledge engineers in specifying and maintaining the procedural and declarative aspects of clinical guideline knowledge, resulting in a machine comprehensible representation. The new framework significantly extends our previous work on the Digital electronic Guidelines Library (DeGeL) The current study designed and implemented a graphical framework for specification of declarative and procedural clinical knowledge, Gesher. We performed three different experiments to evaluate the functionality and usability of the major aspects of the new framework: Specification of procedural clinical knowledge, specification of declarative clinical knowledge, and exploration of a given clinical guideline. The subjects included clinicians and knowledge engineers (overall, 27 participants). The evaluations indicated high levels of completeness and correctness of the guideline specification process by both the clinicians and the knowledge engineers, although the best results, in the case of declarative-knowledge specification, were achieved by teams including a clinician and a knowledge engineer. The usability scores were high as well, although the clinicians’ assessment was significantly lower than the assessment of the knowledge engineers. PMID:21611137

  6. ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

    PubMed Central

    Yamauchi, Yoshio; Yokoyama, Shinji; Chang, Ta-Yuan

    2016-01-01

    Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. PMID:26497474

  7. Ion-polycyclic aromatic hydrocarbon collisions: kinetic energy releases for specific fragmentation channels

    NASA Astrophysics Data System (ADS)

    Reitsma, G.; Zettergren, H.; Boschman, L.; Bodewits, E.; Hoekstra, R.; Schlathölter, T.

    2013-12-01

    We report on 30 keV He2 + collisions with naphthalene (C10H8) molecules, which leads to very extensive fragmentation. To unravel such complex fragmentation patterns, we designed and constructed an experimental setup, which allows for the determination of the full momentum vector by measuring charged collision products in coincidence in a recoil ion momentum spectrometer type of detection scheme. The determination of fragment kinetic energies is found to be considerably more accurate than for the case of mere coincidence time-of-flight spectrometers. In fission reactions involving two cationic fragments, typically kinetic energy releases of 2-3 eV are observed. The results are interpreted by means of density functional theory calculations of the reverse barriers. It is concluded that naphthalene fragmentation by collisions with keV ions clearly is much more violent than the corresponding photofragmentation with energetic photons. The ion-induced naphthalene fragmentation provides a feedstock of various small hydrocarbonic species of different charge states and kinetic energy, which could influence several molecule formation processes in the cold interstellar medium and facilitates growth of small hydrocarbon species on pre-existing polycyclic aromatic hydrocarbons.

  8. Influence of drying procedure and of low degree of substitution on the structural and drug release properties of carboxymethyl starch.

    PubMed

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2010-06-01

    The aim of this study was to investigate the influence of drying methods and low range of degrees of substitution (DS) on the structural, physicochemical, and drug-release properties of carboxymethyl high-amylose starch (CMS). CMS with three DS of 0.03, 0.14, and 0.25 was synthesized and dried by either solvent precipitation (SP), spray drying (SD), or lyophilization (Ly). DS had an influence on the crystalline structure of CMS. It was found that a DS of 0.14 or higher induced a modification of polymorphism. The drying method and the DS had both an impact on the physical properties of the CMS powder which can further influence the formulation characteristics and drug-release properties from monolithic tablets. The CMS with DS of 0.14 and 0.25 dried by SP or SD presented good excipient properties in terms of compressibility. With acetaminophen (20%) as tracer, the monolithic CMS tablets showed controlled drug release over 17 h for DS of 0.14 and 10 h for DS of 0.25, almost independent of pH, suggesting interesting properties for sustained release applications.

  9. Gas tungsten arc and shielded metal arc welding of chromium-nickel steel. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-303-ASME-3 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of 300 Series Cr-Ni steels (P-8-1), in thickness range 0.25 to 2 in.; filler metals are ER3XX (F-6, A-8) (GTAW) and E3XX-15 (F-5, A-8); shielding gas for GTAW is argon.

  10. Gas tungsten arc and shielded metal arc welding of AISI 41XX steels. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.

    1985-08-01

    Procedure WPS-127 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of AISI 4130 and 4142 steels (ASTM A519) (P-No: None), 0.438-in. wall pipe; filler metal is AMS 6457, Class 4130 MC (F-, A-No; None) (GTAW) and E8018-B2L (F-4, A-3) (GMAW); shielding gas is argon (GTAW).

  11. Gas tungsten arc and low hydrogen shielded metal arc welding of carbon steel. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-128-ASME-1 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and low hydrogen shielded metal arc welding of carbon steels (P-1-1), in thickness range 0.25 to 2 inch; filler metals are ER70S-3 (F-6, A-1) (GTAW) and E7018 (F-4, A-1); shielding gas is argon (GTAW).

  12. Manual gas tungsten arc and semiautomatic gas metal arc welding of carbon steel. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-107-ASME-1 is qualified under Section IX of the ASME Boiler and Vessel Code for manual gas tungsten arc and semiautomatic gas metal arc welding of carbon steel (P-1-1), in thickness range 0.237 to 2.0 inch; filler metal is ER70S-3 (F-6, A-1); shielding gas for GTAW is argon, and for GMAW is 95-5 argon-oxygen.

  13. Welding procedure specification: gas tungsten arc and shielded metal arc welding of carbon steel

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-104-ASME-2 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of carbon steels (P-1-1), in thickness range 0.25 to 1 in.; filler metals are E70S-3 (F-6, A-1) (GTAW) and E6010 (F-3, A-1) (SMAW); shielding gas is argon (GTAW).

  14. Acute Effect of Manganese on Hypothalamic Luteinizing Hormone Releasing Hormone Secretion in Adult Male Rats: Involvement of Specific Neurotransmitter Systems

    PubMed Central

    Prestifilippo, Juan Pablo; Fernández-Solari, Javier; De Laurentiis, Andrea; Mohn, Claudia Ester; de la Cal, Carolina; Reynoso, Roxana; Dees, W. Les; Rettori, Valeria

    2008-01-01

    Manganese chloride (MnCl2) is capable of stimulating luteinizing hormone releasing hormone (LHRH) secretion in adult male Sprague-Dawley rats through the activation of the hypothalamic nitric oxide/cyclic guanosine monophosphate (cGMP)/protein kinase G pathway. The present study aimed to determine the involvement of specific neurotransmitters involved in this action. Our results indicate that dopamine, but not glutamic acid and prostaglandinds, mediates the MnCl2 stimulated secretion of LHRH from medial basal hypothalami in vitro, as well as increases the activity of nitric oxide synthase. Furthermore, a biphasic response was observed in that gamma aminobutyric acid (GABA) release was also increased, which acts to attenuate the MnCl2 action to stimulate LHRH secretion. Although it is clear that manganese (Mn+2) can acutely induce LHRH secretion in adult males, we suggest that the additional action of MnCl2 to release GABA, a LHRH inhibitor, may ultimately contribute to suppressed reproductive function observed in adult animals following exposure to high chromic levels of Mn+2. PMID:18603625

  15. Negligible particle-specific toxicity mechanism of silver nanoparticles: the role of Ag+ ion release in the cytosol.

    PubMed

    De Matteis, Valeria; Malvindi, Maria Ada; Galeone, Antonio; Brunetti, Virgilio; De Luca, Elisa; Kote, Sachin; Kshirsagar, Prakash; Sabella, Stefania; Bardi, Giuseppe; Pompa, Pier Paolo

    2015-04-01

    Toxicity of silver nanoparticles (AgNPs) is supported by many observations in literature, but no mechanism details have been proved yet. Here we confirm and quantify the toxic potential of fully characterized AgNPs in HeLa and A549 cells. Notably, through a specific fluorescent probe, we demonstrate the intracellular release of Ag(+) ions in living cells after nanoparticle internalization, showing that in-situ particle degradation is promoted by the acidic lysosomal environment. The activation of metallothioneins in response to AgNPs and the possibility to reverse the main toxic pathway by Ag(+) chelating agents demonstrate a cause/effect relationship between ions and cell death. We propose that endocytosed AgNPs are degraded in the lysosomes and the release of Ag(+) ions in the cytosol induces cell damages, while ions released in the cell culture medium play a negligible effect. These findings will be useful to develop safer-by-design nanoparticles and proper regulatory guidelines of AgNPs. From the clinical editor: The authors describe the toxic potential of silver nanoparticles (AgNP) in human cancer cell lines. Cell death following the application of AgNPs is dose-dependent, and it is mostly due to Ag+ ions. Further in vivo studies should be performed to gain a comprehensive picture of AgNP-toxicity in mammals. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Specific Adsorption via Peptide Tags: Oriented Grafting and Release of Growth Factors for Tissue Engineering.

    PubMed

    Murschel, Frederic; Zaimi, Aldo; Noel, Samantha; Jolicoeur, Mario; De Crescenzo, Gregory

    2015-11-09

    Numerous strategies have been proposed to decorate biomaterials with growth factors (GFs) for tissue engineering applications; their practicability as clinical tools, however, remains uncertain. We previously presented two complementary amphipathic peptides, namely, E5 and K5, which could be utilized as tags to direct GF capture onto organic materials via E5/K5 coiled-coil interactions. We here investigated their potential as mediators of GF physical adsorption. Enzyme-linked immunosorbent assays highlighted that both electrostatic and hydrophobic interactions could contribute to the adsorption process, without interfering with the peptides propensity for coiled-coil interactions. E5-tagged vascular endothelial growth factor, in particular, was efficiently adsorbed to poly(allylamine)-functionalized polystyrene, was maintained in a bioactive state and was steadily liberated over several days with little initial burst. This simple immobilization procedure was successfully applied to poly(ethylene terephthalate) films. Altogether, our data demonstrated that coil-tag-directed adsorption is a tunable, versatile and straightforward strategy to decorate biomaterials with GFs.

  17. A Simple and Rapid Procedure for the Detection of Genes Encoding Shiga Toxins and Other Specific DNA Sequences

    PubMed Central

    Nejman-Faleńczyk, Bożena; Bloch, Sylwia; Januszkiewicz, Aleksandra; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2015-01-01

    A novel procedure for the detection of specific DNA sequences has been developed. This procedure is based on the already known method employing PCR with appropriate primers and a sequence-specific DNA probe labeled with the fluorescent agent 6-carboxylfluorescein (FAM) at the 5′ end and the fluorescence quencher BHQ-1 (black hole quencher) at the 3′ end. However, instead of the detection of the fluorescence signal with the use of real-time PCR cyclers, fluorescence/luminescence spectrometers or fluorescence polarization readers, as in all previously-reported procedures, we propose visual observation of the fluorescence under UV light directly in the reaction tube. An example for the specific detection of the Shiga toxin-producing Escherichia coli (STEC) strains, by detecting Shiga toxin genes, is demonstrated. This method appears to be specific, simple, rapid and cost effective. It may be suitable for use in research laboratories, as well as in diagnostic units of medical institutions, even those equipped only with a thermocycler and a UV transilluminator, particularly if rapid identification of a pathogen is required. PMID:26580652

  18. A simple and rapid procedure for the detection of genes encoding Shiga toxins and other specific DNA sequences.

    PubMed

    Nejman-Faleńczyk, Bożena; Bloch, Sylwia; Januszkiewicz, Aleksandra; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2015-11-13

    A novel procedure for the detection of specific DNA sequences has been developed. This procedure is based on the already known method employing PCR with appropriate primers and a sequence-specific DNA probe labeled with the fluorescent agent 6-carboxylfluorescein (FAM) at the 5' end and the fluorescence quencher BHQ-1 (black hole quencher) at the 3' end. However, instead of the detection of the fluorescence signal with the use of real-time PCR cyclers, fluorescence/luminescence spectrometers or fluorescence polarization readers, as in all previously-reported procedures, we propose visual observation of the fluorescence under UV light directly in the reaction tube. An example for the specific detection of the Shiga toxin-producing Escherichia coli (STEC) strains, by detecting Shiga toxin genes, is demonstrated. This method appears to be specific, simple, rapid and cost effective. It may be suitable for use in research laboratories, as well as in diagnostic units of medical institutions, even those equipped only with a thermocycler and a UV transilluminator, particularly if rapid identification of a pathogen is required.

  19. Arthroscopic biceps ulnar release procedure (BURP): technique description and in vitro assessment of the association of visual control and surgeon experience to regional damage and tenotomy completeness.

    PubMed

    Wilson, David M; Goh, Clara S S; Palmer, Ross H

    2014-08-01

    (1) Describe arthroscopic BURP surgical technique, (2) assess association of visual control and surgeon experience to tenotomy completeness and regional iatrogenic tissue damage. Cadaveric study. Canine cadavers weighing >20 kg (n = 16; 32 elbows). Phase 1 = dissection/anatomic description/procedural refinement (n = 6). Phase 2 = technique description (n = 6). Phase 3 = association of surgeon experience and procedural visual control to tenotomy completion and regional iatrogenic damage (n = 20). Elbows were randomly assigned via coin toss to an experienced- or inexperienced-arthroscopist. Using conventional medial portals, surgeons sought to identify the medial collateral ligament (MCL) and ulnar insertion of the biceps tendon (uBT) before attempting complete tenotomy. Upon procedural completion, surgeons assigned a standardized "visual control score" (VCS) describing viewing that governed procedure and predicted % uBT release, MCL, and median nerve damage. Post-procedural dissection determined actual tenotomy completion and iatrogenic tissue damage. Complete BURP was achieved in 16 of 19 elbows. VCS was associated with tenotomy completeness (P < .01). "Blind" BURP was incomplete in both elbows in which it was attempted. Perception of complete BURP was associated with complete release (P < .01). MCL damage occurred in 10% of elbows. Surgeon experience did not influence VCS, regional damage, or BURP completeness. In canine cadavers, arthroscopic BURP can be consistently performed using conventional arthroscopic instruments and portals by both experienced and inexperienced arthroscopists when visual control guides the tenotomy into the distal aspect of the tendon. © Copyright 2014 by The American College of Veterinary Surgeons.

  20. Impact of Technique-Specific Operative Videos on First-Year Dental Students' Performance of Restorative Procedures.

    PubMed

    Patel, Shalizeh A; Barros, Juliana A; Clark, Christina M; Frey, Gary N; Streckfus, Charles F; Quock, Ryan L

    2015-09-01

    The aim of this study was to examine the impact of psychomotor operative video demonstrations on first-year dental students who are performing specific procedures for the first time in a preclinical setting. The class was randomly divided into two groups, and three restorative procedures were selected. On the date on which each procedure was to be performed in the preclinical laboratory for the first time, one group (experimental, n=50) was shown a technique video for that specific procedure immediately before commencing the exercise; the control cohort (n=50) did not view the video. Technical performance on procedures was evaluated by students and two calibrated and blinded examiners. The students' perceptions of the experience were also collected in a survey. All first-year students participated in the study, for a 100% response rate. A Mann-Whitney U test did not show any group differences in technical performance (mean values on preparation: 77.1 vs. 77.8; amalgam: 82.7 vs. 82.8; composite: 79.7 vs. 78.0). A Spearman rho test revealed a significantly higher correlation in 13 out of 25 evaluation categories between student self-assessment and blinded examiner assessment for the experimental group. A chi-square test of questionnaire responses revealed a positive student perception of administering these videos for the preparation (X(2)=4.8, p<0.03), the amalgam restoration (X(2)=12.4, p<0.001), and the composite restoration (X(2)=11.3, p<0.001). The psychomotor video demonstrations did not immediately improve student performance on preclinical operative procedures, but they were well received by students and augmented self-assessment ability. These findings suggest that videos can be a useful teaching aid in a preclinical environment, especially regarding comprehension of concepts.

  1. Changes in antibody specificities and cytokine release after infection with lactate dehydrogenase-elevating virus.

    PubMed

    Aparicio, José L; Saxena, Anubha; Coutelier, Jean-Paul; Van Snick, Jacques; Retegui, Lilia A

    2013-03-01

    Lactate dehydrogenase-elevating virus (LDV) is an apparently innocuous and persistent virus that can modify mouse immune reactions. We have shown that LDV-infected mice immunized with human growth hormone (hGH) showed a deep modification of the specificity of the anti-hGH antibodies (Ab) in CBA/Ht mice but not BALB/c animals. The aim of this work was to extend the previous observations to another mouse strain, C57BL/6, as well as to an antigen unrelated to hGH, ovalbumin (OVA), and to explore at the same time the production of various cytokines at serum and cellular levels. The amount of Ab directed to hGH or OVA native antigenic determinants versus the concentration of Ab to cryptic epitopes was evaluated by ELISA competition experiments. Results indicated that LDV infection affected Ab specificity solely in CBA/Ht mice. In CBA/Ht the virus infection was associated with a reduction of the Ab titers to hGH native epitopes and with a decrease of IL-13 and IL-17 serum levels, but Ab to native OVA epitopes were increased with a simultaneous increase of IL-17. Accordingly, only lymph node cells from infected CBA/Ht mice immunized with OVA were found to produce INF-γ, IL-13 and IL-17. Thus, a correlation of cytokine production with a change in Ab specificity after a viral infection was found, although this phenomenon was restricted to a given antigen and to the genetic background of immunized animals. These observations suggest that an apparent harmless virus can affect some immunological mechanisms, which could lead, for example, to inflammatory or autoimmune disorders.

  2. Tissue-specific hormonal profiling during dormancy release in macaw palm seeds.

    PubMed

    Ribeiro, Leonardo M; Garcia, Queila S; Müller, Maren; Munné-Bosch, Sergi

    2015-04-01

    Little is known about the control exerted by hormones in specific tissues during germination and post-germinative development in monocot seeds, whose embryos have complex structures and can remain dormant for long periods of time. Here the tissue-specific hormonal profile of macaw palm (Acrocomia aculeata) seeds overcoming dormancy and seedling during initial development was examined. Endogenous hormonal concentrations were determined in the cotyledonary petiole, haustorium, operculum, endosperm adjacent to the embryo and peripheral endosperm of dry dormant seeds, imbibed seeds trapped in phase I of germination, and germinating (phase 2 and phase 3) seeds 2, 5, 10 and 15 days after sowing. Evaluations were performed on seeds treated for overcoming dormancy by removal of the operculum and by immersion in a gibberellic acid (GA3 ) solution. Removal of the operculum effectively helped in overcoming dormancy, which was associated with the synthesis of active gibberellins (GAs) and cytokinins (CKs), as well as reductions of abscisic acid (ABA) in the cotyledonary petiole. In imbibed seeds trapped in phase I of germination, exogenous GA3 caused an increase in active GAs in the cotyledonary petiole and operculum and reduction in ABA in the operculum. Initial seedling development was associated with increases in the CK/auxin ratio in the haustorium and GA levels in the endosperm which is possibly related to the mobilization of metabolic reserves. Increases in salicylic acid (SA) and jasmonic acid (JA) concentrations were associated with the development of the vegetative axis. Hormones play a crucial tissue-specific role in the control of dormancy, germination and initial development of seedlings in macaw palm, including a central role not only for GAs and ABA, but also for CKs and other hormones.

  3. Developing site-specific interactive environmental management tools: An exciting method of communicating training, procedures, and other information

    SciTech Connect

    Jaeckels, J.M.

    1999-07-01

    Environmental managers are faced with numerous programs that must be communicated throughout their organizations. Among these are regulatory training programs, internal environmental policy, regulatory guidance/procedures and internal guidance/procedures. Traditional methods of delivering this type of information are typically confined to written materials and classroom training. There are many challenges faced by environmental managers with these traditional approaches including: determining if recipients of written plans or procedures are reading and comprehending the information; scheduling training sessions to reach all affected people across multiple schedules/shifts; and maintaining adequate training records. In addition, current trends toward performance-based or competency-based training requires a more consistent method of measuring and documenting performance. The use of interactive computer applications to present training or procedural information is a new and exciting tool for delivering environmental information to employees. Site-specific pictures, text, sound, and even video can be combined with multimedia software to create informative and highly interactive applications. Some of the applications that can be produced include integrated environmental training, educational pieces, and interactive environmental procedures. They can be executed from a CD-ROM, hard drive, network or a company Intranet. Collectively, the authors refer to these as interactive environmental management tools (IEMTs). This paper focuses on site-specific, interactive training as an example of an IEMT. Interactive training not only delivers a highly effective message, but can also be designed to focus on site-specific environmental issues that are unique to each company. Interactive training also lends itself well to automated record keeping functions and to reaching all affected employees.

  4. Probing the intracellular organic matters released from the photocatalytic inactivation of bacteria using fractionation procedure and excitation-emission-matrix fluorescence.

    PubMed

    Huang, Guocheng; Ng, Tsz Wai; An, Taicheng; Li, Guiying; Xia, Dehua; Yip, Ho Yin; Zhao, Huijun; Wong, Po Keung

    2017-03-01

    Photocatalysis provides a "green" and effective strategy for water disinfection. During the photocatalytic disinfection process, intracellular organic matter (IOM) from bacterial cells may be released into the bulk solution. In this study, the role of released IOM in the photocatalytic bacterial inactivation was investigated by fractionation procedure and fluorescence excitation-emission-matrix (EEM) combined with parallel factor analysis (PARAFAC) approaches. The normal bacterial cells treated by TiO2-UVA in the presence and absence with fractionated IOM results implied that the released IOM would be either absorbed on the surface of the photocatalysts or reacted by the photo-generated reactive species, and thereby affecting the kinetics of photocatalytic bacterial inactivation. Fluorescence EEM-PARAFAC results showed that two components (C1 and C3) associated with tryptophan- and tyrosine-like proteins were released. While another two components (C2 and C4) were the oxidation products, and their intensities were found to negatively correlate with those of C1 and C3, respectively. Microtox(®) test results indicated that toxicity occurred during the photocatalytic bacterial inactivation process. The toxicity was found to decrease after the bacteria were completely inactivated, and completely removed if provided a sufficient reaction time. Of particular interest is that a significant high linear correlation was observed between the toxicity and the maximum fluorescence intensity of C4. The results and information obtained in this study will be important for further developing photocatalysis in water/wastewater disinfection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Estimation of peacock bass (Cichla spp.) mortality rate during catch-release fishing employing different post-capture procedures.

    PubMed

    Barroco, L S A; Freitas, C E C; Lima, Á C

    2017-08-17

    The effect of catch-and-release fishing on the survival of peacock bass (Cichla spp.) was evaluated by comparing two types of artificial bait (jig and shallow-diver plugs) and two types of post-catch confinement. Two experiments were conducted during the periods January-February and October-November 2012 in the Unini River, a right-bank tributary of the Negro River. In total, 191 peacock bass were captured. Both groups of fish were subjected to experimental confinement (collective and individual) for three days. Additionally, 11 fish were tagged with radio transmitters for telemetry monitoring. Mortality rate was estimated as the percentage of dead individuals for each type of bait and confinement. For peacock bass caught with jig baits, mortality was zero. The corresponding figure for shallow-diver bait was 1.66% for fish in collective containment, 18.18% for fish monitored by telemetry and 0% for individuals confined individually. Our results show low post-release mortality rates for peacock bass. Furthermore, neither the type of confinement nor the type of bait had a statistically significant influence on mortality rates. While future studies could include other factors in the analysis, our results show that catch-and-release fishing results in low mortality rates.

  6. Procedural learning deficits in specific language impairment (SLI): A meta-analysis of serial reaction time task performance☆

    PubMed Central

    Lum, Jarrad A.G.; Conti-Ramsden, Gina; Morgan, Angela T.; Ullman, Michael T.

    2014-01-01

    Meta-analysis and meta-regression were used to evaluate whether evidence to date demonstrates deficits in procedural memory in individuals with specific language impairment (SLI), and to examine reasons for inconsistencies of findings across studies. The Procedural Deficit Hypothesis (PDH) proposes that SLI is largely explained by abnormal functioning of the frontal-basal ganglia circuits that support procedural memory. It has also been suggested that declarative memory can compensate for at least some of the problems observed in individuals with SLI. A number of studies have used Serial Reaction Time (SRT) tasks to investigate procedural learning in SLI. In this report, results from eight studies that collectively examined 186 participants with SLI and 203 typically-developing peers were submitted to a meta-analysis. The average mean effect size was .328 (CI95: .071, .584) and was significant. This suggests SLI is associated with impairments of procedural learning as measured by the SRT task. Differences among individual study effect sizes, examined with meta-regression, indicated that smaller effect sizes were found in studies with older participants, and in studies that had a larger number of trials on the SRT task. The contributions of age and SRT task characteristics to learning are discussed with respect to impaired and compensatory neural mechanisms in SLI. PMID:24315731

  7. Longitudinal and transverse magnetic field program procedure and detailed specification for Sigma 5

    NASA Technical Reports Server (NTRS)

    Wang, C. K.

    1980-01-01

    A computer program and procedure for plotting the contour of the data transferred from the Marshall Space Flight Center solar magnetography is presented. The plotted data then can be easily compared with solar data from other sources, such as the Solar Maximum Mission. From the data file for circular polarization the longitudinal program plots the contours for filtered longitudinal plot and intensity plot by choosing the positive and negative contour levels, intensity levels, and also X,Y plotting ranges which need to be used. In a similar manner the transverse program generates the transverse contour plot, azimuth plot, and intensity plot from the linear polarization data files.

  8. Stomach-specific controlled release gellan beads of acid-soluble drug prepared by ionotropic gelation method.

    PubMed

    Narkar, Mrunalini; Sher, Praveen; Pawar, Atmaram

    2010-03-01

    The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using 3(2) factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful in H. pylori treatment.

  9. [Nutrient use efficiency and yield-increasing effect of single basal application of rice specific controlled release fertilizer].

    PubMed

    Chen, Jiansheng; Xu, Peizhi; Tang, Shuanhu; Zhang, Fabao; Xie, Chunsheng

    2005-10-01

    A series of pot and field experiments and field demonstrations showed that in comparing with the commonly used specific-fertilizers containing same amounts of nutrients, single basal application of rice-specific controlled release fertilizer could increase the use efficiency of N and P by 12.2% - 22.7% and 7.0% - 35.0%, respectively in pot experiment, and the use efficiency of N by 17.1% in field experiment. In 167 field demonstrations successively conducted for 3 years in various rice production areas of Guangdong Province, single basal application of the fertilizer saved the application rate of N and P by 22.1% and 21.8%, respectively, and increased the yield by 8.2%, compared with normal split fertilization.

  10. Procedure-specific Risks of Thrombosis and Bleeding in Urological Non-cancer Surgery: Systematic Review and Meta-analysis.

    PubMed

    Tikkinen, Kari A O; Craigie, Samantha; Agarwal, Arnav; Siemieniuk, Reed A C; Cartwright, Rufus; Violette, Philippe D; Novara, Giacomo; Naspro, Richard; Agbassi, Chika; Ali, Bassel; Imam, Maha; Ismaila, Nofisat; Kam, Denise; Gould, Michael K; Sandset, Per Morten; Guyatt, Gordon H

    2017-03-09

    Pharmacological thromboprophylaxis involves a trade-off between a reduction in venous thromboembolism (VTE) and increased bleeding. No guidance specific for procedure and patient factors exists in urology. To inform estimates of absolute risk of symptomatic VTE and bleeding requiring reoperation in urological non-cancer surgery. We searched for contemporary observational studies and estimated the risk of symptomatic VTE or bleeding requiring reoperation in the 4 wk after urological surgery. We used the GRADE approach to assess the quality of the evidence. The 37 eligible studies reported on 11 urological non-cancer procedures. The duration of prophylaxis varied widely both within and between procedures; for example, the median was 12.3 d (interquartile range [IQR] 3.1-55) for open recipient nephrectomy (kidney transplantation) studies and 1 d (IQR 0-1.3) for percutaneous nephrolithotomy, open prolapse surgery, and reconstructive pelvic surgery studies. Studies of open recipient nephrectomy reported the highest risks of VTE and bleeding (1.8-7.4% depending on patient characteristics and 2.4% for bleeding). The risk of VTE was low for 8/11 procedures (0.2-0.7% for patients with low/medium risk; 0.8-1.4% for high risk) and the risk of bleeding was low for 6/7 procedures (≤0.5%; no bleeding estimates for 4 procedures). The quality of the evidence supporting these estimates was low or very low. Although inferences are limited owing to low-quality evidence, our results suggest that extended prophylaxis is warranted for some procedures (eg, kidney transplantation procedures in high-risk patients) but not others (transurethral resection of the prostate and reconstructive female pelvic surgery in low-risk patients). The best evidence suggests that the benefits of blood-thinning drugs to prevent clots after surgery outweigh the risks of bleeding in some procedures (such as kidney transplantation procedures in patients at high risk of clots) but not others (such as prostate

  11. Efficient Noninferiority Testing Procedures for Simultaneously Assessing Sensitivity and Specificity of Two Diagnostic Tests.

    PubMed

    Shan, Guogen; Amei, Amei; Young, Daniel

    2015-01-01

    Sensitivity and specificity are often used to assess the performance of a diagnostic test with binary outcomes. Wald-type test statistics have been proposed for testing sensitivity and specificity individually. In the presence of a gold standard, simultaneous comparison between two diagnostic tests for noninferiority of sensitivity and specificity based on an asymptotic approach has been studied by Chen et al. (2003). However, the asymptotic approach may suffer from unsatisfactory type I error control as observed from many studies, especially in small to medium sample settings. In this paper, we compare three unconditional approaches for simultaneously testing sensitivity and specificity. They are approaches based on estimation, maximization, and a combination of estimation and maximization. Although the estimation approach does not guarantee type I error, it has satisfactory performance with regard to type I error control. The other two unconditional approaches are exact. The approach based on estimation and maximization is generally more powerful than the approach based on maximization.

  12. Light-stimulated cargo release from a core-shell structured nanocomposite for site-specific delivery

    NASA Astrophysics Data System (ADS)

    Cai, Yun; Ling, Li; Li, Xiaofang; Chen, Meng; Su, Likai

    2015-03-01

    This paper reported a core-shell structured site-specific delivery system with a light switch triggered by low energy light (λ=510 nm). Its core was composed of supermagnetic Fe3O4 nanoparticles for magnetic guiding and targeting. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for cargo capacity. A light switch N1-(4aH-cyclopenta[1,2-b:5,4-b‧]dipyridin-5(5aH)-ylidene)benzene-1,4-diamine (CBD) was covalently grafted into these hexagonal tunnels, serving as light stimuli acceptor with loading content of 1.1 μM/g. This composite was fully characterized and confirmed by SEM, TEM, XRD patterns, N2 adsorption/desorption, thermogravimetric analysis, IR, UV-vis absorption and emission spectra. Experimental data suggested that this composite had a core as wide as 150 nm and could be magnetically guided to specific sites. Its hexagonal tunnels were as long as 180 nm. Upon light stimuli of "on" and "off" states, controllable release was observed with short release time of ~900 s (90% capacity).

  13. Resistant starch film-coated microparticles for an oral colon-specific polypeptide delivery system and its release behaviors.

    PubMed

    Situ, Wenbei; Chen, Ling; Wang, Xueyu; Li, Xiaoxi

    2014-04-23

    For the delivery of bioactive components to the colon, an oral colon-specific controlled release system coated with a resistant starch-based film through aqueous dispersion coating process was developed. Starch was modified by a high-temperature-pressure reaction, enzymatic debranching, and retrogradation, resulting in a dramatic increase in the resistibility against enzymatic digestion (meaning the formation of resistant starch, specifically RS3). This increase could be associated with an increase in the relative crystallinity, a greater amount of starch molecular aggregation structure, and the formation of a compact mass fractal structure, resulting from the treatment. The microparticles coated with this RS3 film showed an excellent controlled release property. In streptozotocin (STZ)-induced type II diabetic rats, the RS3 film-coated insulin-loaded microparticles exhibited the ability to steadily decrease the plasma glucose level initially and then maintain the plasma glucose level within the normal range for total 14-22 h with different insulin dosages after oral administration; no glycopenia or glycemic fluctuation was observed. Therefore, the potential of this new RS3 film-coated microparticle system has been demonstrated for the accurate delivery of bioactive polypeptides or protein to the colon.

  14. Striatal neurones have a specific ability to respond to phasic dopamine release.

    PubMed

    Castro, Liliana R V; Brito, Marina; Guiot, Elvire; Polito, Marina; Korn, Christoph W; Hervé, Denis; Girault, Jean-Antoine; Paupardin-Tritsch, Danièle; Vincent, Pierre

    2013-07-01

      The cAMP/protein kinase A (PKA) signalling cascade is ubiquitous, and each step in this cascade involves enzymes that are expressed in multiple isoforms. We investigated the effects of this diversity on the integration of the pathway in the target cell by comparing prefrontal cortical neurones with striatal neurones which express a very specific set of signalling proteins. The prefrontal cortex and striatum both receive dopaminergic inputs and we analysed the dynamics of the cAMP/PKA signal triggered by dopamine D1 receptors in these two brain structures. Biosensor imaging in mouse brain slice preparations showed profound differences in the D1 response between pyramidal cortical neurones and striatal medium spiny neurones: the cAMP/PKA response was much stronger, faster and longer lasting in striatal neurones than in pyramidal cortical neurones. We identified three molecular determinants underlying these differences: different activities of phosphodiesterases, particularly those of type 4, which strongly damp the cAMP signal in the cortex but not in the striatum; stronger adenylyl cyclase activity in the striatum, generating responses with a faster onset than in the cortex; and DARPP-32, a phosphatase inhibitor which prolongs PKA action in the striatum. Striatal neurones were also highly responsive in terms of gene expression since a single sub-second dopamine stimulation is sufficient to trigger c-Fos expression in the striatum, but not in the cortex. Our data show how specific molecular elements of the cAMP/PKA signalling cascade selectively enable the principal striatal neurones to respond to brief dopamine stimuli, a critical process in incentive learning.

  15. Comparison of 2015 Medicare relative value units for gender-specific procedures: Gynecologic and gynecologic-oncologic versus urologic CPT coding. Has time healed gender-worth?

    PubMed

    Benoit, M F; Ma, J F; Upperman, B A

    2017-02-01

    In 1992, Congress implemented a relative value unit (RVU) payment system to set reimbursement for all procedures covered by Medicare. In 1997, data supported that a significant gender bias existed in reimbursement for gynecologic compared to urologic procedures. The present study was performed to compare work and total RVU's for gender specific procedures effective January 2015 and to evaluate if time has healed the gender-based RVU worth. Using the 2015 CPT codes, we compared work and total RVU's for 50 pairs of gender specific procedures. We also evaluated 2015 procedure related provider compensation. The groups were matched so that the procedures were anatomically similar. We also compared 2015 to 1997 RVU and fee schedules. Evaluation of work RVU's for the paired procedures revealed that in 36 cases (72%), male vs female procedures had a higher wRVU and tRVU. For total fee/reimbursement, 42 (84%) male based procedures were compensated at a higher rate than the paired female procedures. On average, male specific surgeries were reimbursed at an amount that was 27.67% higher for male procedures than for female-specific surgeries. Female procedure based work RVU's have increased minimally from 1997 to 2015. Time and effort have trended towards resolution of some gender-related procedure worth discrepancies but there are still significant RVU and compensation differences that should be further reviewed and modified as surgical time and effort highly correlate. Copyright © 2016. Published by Elsevier Inc.

  16. Association between polymorphisms in the prostate-specific antigen (PSA) promoter and release of PSA.

    PubMed

    Sävblom, C; Giwercman, A; Malm, J; Halldén, C; Lundin, K; Lilja, H; Giwercman, Y

    2009-10-01

    Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte DNA was extracted from 291 conscripts and genotyping performed with the Sequenom Mass Array System. PSA was measured with an immunofluorometric assay. Linear regression analysis was used to test the association of polymorphism frequencies with serum and seminal plasma levels of PSA. PSA gene polymorphisms at -158 bp or -4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in blood. Homozygotes for the A-allele at -158 bp in combination with CAG > 22 had significantly higher serum levels of tPSA than subjects carrying the G-allele (p = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by interactions between PSA promoter variants and AR CAG polymorphism.

  17. Site-specific cation release drives actin filament severing by vertebrate cofilin

    PubMed Central

    Kang, Hyeran; Bradley, Michael J.; Cao, Wenxiang; Zhou, Kaifeng; Grintsevich, Elena E.; Michelot, Alphée; Sindelar, Charles V.; Hochstrasser, Mark; De La Cruz, Enrique M.

    2014-01-01

    Actin polymerization powers the directed motility of eukaryotic cells. Sustained motility requires rapid filament turnover and subunit recycling. The essential regulatory protein cofilin accelerates network remodeling by severing actin filaments and increasing the concentration of ends available for elongation and subunit exchange. Although cofilin effects on actin filament assembly dynamics have been extensively studied, the molecular mechanism of cofilin-induced filament severing is not understood. Here we demonstrate that actin filament severing by vertebrate cofilin is driven by the linked dissociation of a single cation that controls filament structure and mechanical properties. Vertebrate cofilin only weakly severs Saccharomyces cerevisiae actin filaments lacking this “stiffness cation” unless a stiffness cation-binding site is engineered into the actin molecule. Moreover, vertebrate cofilin rescues the viability of a S. cerevisiae cofilin deletion mutant only when the stiffness cation site is simultaneously introduced into actin, demonstrating that filament severing is the essential function of cofilin in cells. This work reveals that site-specific interactions with cations serve a key regulatory function in actin filament fragmentation and dynamics. PMID:25468977

  18. Gender-specific differences in biomarkers responses to acute coronary syndromes and revascularization procedures.

    PubMed

    Sbarouni, Eftihia; Georgiadou, Panagiota; Voudris, Vassilis

    2011-09-01

    A growing body of gender-related research in coronary artery disease is beginning to gradually elucidate differences between women and men. In patients presenting with acute coronary syndromes (ACS), these sex differences include varying risk factor profiles, accuracy of diagnostic testing, clinical presentations, treatment practices and outcomes. There is also a differential expression of cardiac biomarkers by sex, which remains unexplained. This paper reviews all the available information on the effect of gender on cardiac biomarkers by search of MEDLINE using the terms gender differences, biomarkers, ACS and revascularization procedures. A better understanding of the sex disparities in biomarkers along with all other clinical information is essential to optimal management and patient care in the future.

  19. A new procedure for the specific high-performance liquid chromatographic determination of hydroxyproline.

    PubMed

    Biondi, P A; Chiesa, L M; Storelli, M R; Renon, P

    1997-11-01

    A procedure suitable for a selective high-performance liquid chromatographic (HPLC) analysis of the imino acid hydroxyproline in the presence of a large excess of amino acids is proposed. To deaminate the amino acids, the well-known reaction with nitrous acid is exploited. The N-nitroso derivatives of imino acids obtained are extracted in ethyl acetate, denitrosated by hydrobromic acid, and treated with dabsyl-chloride. The final HPLC separations are carried out on a reversed-phase column in a rapid isocratic run. The use of the cis isomer of hydroxyproline as an internal standard allows good reproducibility. As an application of the described method, the hydroxyproline content in samples containing collagen and an excess of bovine serum albumine (up to 20:1) is determined.

  20. 7 CFR 1484.35 - Must Cooperators follow specific contracting procedures?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS PROGRAMS TO HELP DEVELOP FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Program Operations § 1484.35 Must Cooperators...) Conduct all contracting in an open manner. Individuals who develop or draft specifications,...

  1. 24 CFR 200.937 - Supplementary specific procedural requirements under HUD building product standards and...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... following standards, which are incorporated by reference: ANSI Z124.1—(1980)Plastic Bathtub Units ANSI Z124... requirements under HUD building product standards and certification program for plastic bathtub units, plastic... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Minimum Property Standards § 200.937 Supplementary specific...

  2. 7 CFR 1484.35 - Must Cooperators follow specific contracting procedures?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... HELP DEVELOP FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Program Operations § 1484.35 Must Cooperators...) Conduct all contracting in an open manner. Individuals who develop or draft specifications, requirements...; (5) Perform some form of price or cost analysis, such as a comparison of price quotations to...

  3. Inositol 1,4,5-trisphosphate binds to a specific receptor and releases microsomal calcium in the arterior pituitary gland

    SciTech Connect

    Guillemette, G.; Balla, T.; Baukal, A.J.; Catt, K.J.

    1987-12-01

    The properties of inositol 1,4,5-trisphosphate (InsP/sub 3/) receptor sites in the anterior pituitary were evaluated by binding studies with InsP/sub 3/ labeled with /sup 32/P to high specific radioactivity. Specific binding of Ins(/sup 32/P)P/sub 3/ was demonstrable in pituitary membrane preparations and was linearly proportional to the amount of membrane added over the range 0.5-2 mg of protein. Kinetic studies showed that specific InsP/sub 3/ binding was half-maximal in about 40 sec and reached a plateau after 15 min at 0/sup 0/C. Scatchard analysis of the binding data was consistent with a single set of high affinity sites. The specificity of Ins(/sup 32/P)P/sub 3/ binding to these sites was illustrated by the much weaker affinity for structural analogs such as inositol 1-phosphate, phytic acid, 2,3-bisphosphoglycerate, and fructose 1,6-bisphosphate. To assess the functional relevance of the InsP/sub 3/ binding sites, the Ca/sup 2 +/-releasing activity of InsP/sub 3/ was measured in pituitary membrane preparations. Under physiological conditions within the cytosol, the high-affinity InsP/sub 3/ binding sites characterized in pituitary membranes could serve as the putative receptors through which InsP/sub 3/ triggers Ca/sup 2 +/ mobilization in the anterior pituitary gland.

  4. Minimizing soil remediation volume through specification of excavation and materials handling procedures

    SciTech Connect

    Oresik, W.L.S.; Otten, M.T.; Nelson, M.D.

    1994-12-31

    The technologies currently available for treating soils contaminated with the explosives 2,4,6-trinitroluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazene (RDX) are both limited and expensive. Therefore, an important consideration in soils remediation is the preparation of construction specifications and contract drawings which limit the volume of soil that will be required to undergo treatment. Construction specifications and contract drawings were developed for the Contaminated Soil Remediation of the Explosives Washout Lagoons at Umatilla Depot Activity (UMDA) with the following primary objectives: (1) limit the volume of soil excavated from the Explosives Washout Lagoons and Explosives Washout Plant Areas, (2) minimize materials handling, and (3) reduce the excavated volume of soil which will undergo treatment.

  5. An automated procedure for the simultaneous determination of specific conductance and pH in natural water samples

    USGS Publications Warehouse

    Eradmann, D.E.; Taylor, H.E.

    1978-01-01

    An automated, continuous-flow system is utilized to determine specific conductance and pH simultaneously in natural waters. A direct electrometric procedure is used to determine values in the range pH 4-9. The specific conductance measurements are made with an electronically modified, commercially available conductivity meter interfaced to a separate module containing the readout control devices and printer. The system is designed to switch ranges automatically to accommodate optimum analysis of widely varying conductances ranging from a few ??mhos cm-1 to 15,000 ??mho cm-1. Thirty samples per hour can be analyzed. Comparison of manual and automated procedures for 40 samples showed that the average differences were 1.3% for specific conductance and 0.07 units for pH. The relative standard deviation for 25 replicate values for each of five samples was significantly less than 1% for the specific conductance determination; the standard deviation for the pH determination was ??? 0.06 pH units. ?? 1978.

  6. A fast and efficient procedure to produce scFvs specific for large macromolecular complexes.

    PubMed

    Wu, Si; Ke, Ailong; Doudna, Jennifer A

    2007-01-10

    We have expanded the application of antibody phage display to a new type of antigen: ribonucleoprotein (RNP) complexes. We describe a simple and efficient method for screening antibodies specific for large intact RNPs and individual components. We also describe a fast and easy method to overcome the abundance of amber stop codons in the positive phage clones. The resulting antibodies have been used in ELISA and Western blot analysis.

  7. High neuropeptide Y release associates with Ewing sarcoma bone dissemination - in vivo model of site-specific metastases.

    PubMed

    Hong, Sung-Hyeok; Tilan, Jason U; Galli, Susana; Izycka-Swieszewska, Ewa; Polk, Taylor; Horton, Meredith; Mahajan, Akanksha; Christian, David; Jenkins, Shari; Acree, Rachel; Connors, Katherine; Ledo, Phuong; Lu, Congyi; Lee, Yi-Chien; Rodriguez, Olga; Toretsky, Jeffrey A; Albanese, Chris; Kitlinska, Joanna

    2015-03-30

    Ewing sarcoma (ES) develops in bones or soft tissues of children and adolescents. The presence of bone metastases is one of the most adverse prognostic factors, yet the mechanisms governing their formation remain unclear. As a transcriptional target of EWS-FLI1, the fusion protein driving ES transformation, neuropeptide Y (NPY) is highly expressed and released from ES tumors. Hypoxia up-regulates NPY and activates its pro-metastatic functions. To test the impact of NPY on ES metastatic pattern, ES cell lines, SK-ES1 and TC71, with high and low peptide release, respectively, were used in an orthotopic xenograft model. ES cells were injected into gastrocnemius muscles of SCID/beige mice, the primary tumors excised, and mice monitored for the presence of metastases. SK-ES1 xenografts resulted in thoracic extra-osseous metastases (67%) and dissemination to bone (50%) and brain (25%), while TC71 tumors metastasized to the lungs (70%). Bone dissemination in SK-ES1 xenografts associated with increased NPY expression in bone metastases and its accumulation in bone invasion areas. The genetic silencing of NPY in SK-ES1 cells reduced bone degradation. Our study supports the role for NPY in ES bone invasion and provides new models for identifying pathways driving ES metastases to specific niches and testing anti-metastatic therapeutics.

  8. Release of 5-amino salicylic acid from acrylic type polymeric prodrugs designed for colon-specific drug delivery.

    PubMed

    Davaran, S; Hanaee, J; Khosravi, A

    1999-04-19

    New acrylic type polymeric systems having degradable ester or amide bonds linked to the bioactive agent 5-amino salicylic acid (5-ASA), were prepared and evaluated as materials for colon-specific drug delivery. Methacryloyloxyethyl 5-amino salicylate (MOES), and N-methacryloylaminoethyl 5-amino salicylamide (MAES) were prepared as the polymerizable derivatives of 5-ASA using activated ester methodology. The drug-containing monomers were free radically copolymerized with methacrylic acid or hydroxyethyl methacrylate, utilizing azobisisobutyronitrile as initiator. The polymer bearing 5-ASA units as side substituents of the acrylic backbone were obtained in the form of poly pendent esters or poly pendent amides. The drug release studies were performed by hydrolysis in buffered solutions (pH 1, 7.2, 8.5), or simulated intestinal fluid containing pancreatin to measure the chemical degradation expected to occur in the intestinal tract. The release profiles indicated that the hydrolytic behavior of polymers strongly depends on their degree of swelling, type of comonomer, and the nature of hydrolyzable bond. Implication of the results for use of these polymers for colon targeting are discussed.

  9. Chemical identification, emission pattern and function of male-specific pheromones released by a rarely swarming locust, Schistocerca americana.

    PubMed

    Stahr, Christiane; Svatoš, Aleš; Seidelmann, Karsten

    2013-01-01

    Pheromones serve key functions in the biology of swarming locusts. However, research has focused largely on the mass-swarming desert locust, Schistocerca gregaria. We extended these investigations to the pheromonal profile of the rarely swarming American bird grasshopper, S. americana (Drury). The headspace of mature gregarious S. americana males contained three characteristic electroantennogram-active components: (Z)-3-nonen-1-ol, (Z)-2-octen-1-ol, and nonanal. These substances were accompanied by aromatics such as phenol that are also released by females and immatures. Male-specific pheromone components were released independently from epidermal gland cells, with the highest emission rate being for (Z)-3-nonen-1-ol from the abdomen and legs. The emission of the major compound, (Z)-3-nonen-1-ol, is stress-sensitive, and coincides with sexual maturity and crowding. The emission pattern strongly supports a role of (Z)-3-nonen-1-ol in the reproductive biology of S. americana. The pheromone is involved in courtship-inhibition and is used as mate assessment pheromone in cryptic female choice. In double mating experiments, females choose sperm of males with high (Z)-3-nonen-1-ol emission. Furthermore the pheromone accelerated maturation of immature adults and supports synchronization of sexual development.

  10. Development of quality control procedures for mass produced and released Bactrocera Philippinensis (Diptera: Tephritidae) for sterile insect technique programs

    SciTech Connect

    Resilva, S.; Obra, G.; Zamora, N.; Gaitan, E.

    2007-03-15

    Quality control procedures for Bactrocera philippinensis Drew and Hancock 1994 (Diptera: Tephritidae) used in sterile insect technique (SIT) programs were established in the mass rearing facility at the Philippine Nuclear Research Institute. Basic studies on pupal irradiation, holding/packaging systems, shipping procedures, longevity, sterility studies, and pupal eye color determination in relation to physiological development at different temperature regimes were investigated. These studies will provide baseline data for the development of quality control protocols for an expansion of B. philippinensis field programs with an SIT component in the future. (author) [Spanish] Los procedimientos de control de calidad para Bactrocera philippinensis Drew y Hancock 1994 (Diptera: Tephritidae) usados en programas de la tecnica de insecto esteril (TIE) fueron establecidos en la facilidad de cria en masa del Instituto Filipino de Investigacion Nuclear. Estudios basicos sobre la irradiacion de las pupas, sistemas de almacenaje/empaque, procedimientos del envio, longevidad, estudios de esterilidad y la determinacion del color de ojo de la pupa en relacion con el desarrollo fisiologico en regimenes diferentes de temperatura fueron investigados. Estos estudios proveeran una linea de informacion basica para el desarrollo de protocolos de control de calidad para una expansion de los programas de campo para B. philippinensis con un componente de TIS en el futuro. (author)

  11. Specific mesenchymal/epithelial induction of olfactory receptor, vomeronasal, and gonadotropin-releasing hormone (GnRH) neurons

    PubMed Central

    Rawson, N.E; Lischka, F. W.; Yee, K.K.; Peters, A.Z.; Tucker, E.S.; Meechan, D.W.; Zirlinger, M.; Maynard, T.M.; Burd, G.B.; Dulac, C.; Pevny, L.; LaMantia, A-S.

    2013-01-01

    We asked whether specific mesenchymal/epithelial (M/E) induction generates olfactory receptor neurons (ORNs), vomeronasal neurons (VRNs) and gonadotropin releasing hormone (GnRH) neurons—the major neuron classes associated with the olfactory epithelium (OE). To assess specificity of M/E-mediated neurogenesis, we compared the influence of frontonasal mesenchyme on frontonasal epithelium, which becomes the OE, with that of the forelimb bud. Despite differences in position, morphogenetic and cytogenic capacity, both mesenchymal tissues support neurogenesis, expression of several signaling molecules and neurogenic transcription factors in the frontonasal epithelium. Only frontonasal mesenchyme, however, supports OE-specific patterning and activity of a subset of signals and factors associated with OE differentiation. Moreover, only appropriate pairing of frontonasal epithelial and mesenchymal partners yields ORNs, VRNs, and GnRH neurons. Accordingly, the position and molecular identity of specialized frontonasal epithelia and mesenchyme early in gestation and subsequent inductive interactions, specifies the genesis and differentiation of peripheral chemosensory and neuroendocrine neurons. PMID:20503368

  12. A Good Manufacturing Practice procedure to engineer donor virus-specific T cells into potent anti-leukemic effector cells.

    PubMed

    van Loenen, Marleen M; de Boer, Renate; van Liempt, Ellis; Meij, Pauline; Jedema, Inge; Falkenburg, J H Frederik; Heemskerk, Mirjam H M

    2014-04-01

    A sequential, two-step procedure in which T-cell-depleted allogeneic stem cell transplantation is followed by treatment with donor lymphocyte infusion at 6 months can significantly reduce the risk and severity of graft-versus-host disease, with postponed induction of the beneficial graft-versus-leukemia effect. However, patients with high-risk leukemia have a substantial risk of relapse early after transplantation, at a time when administration of donor lymphocytes has a high likelihood of resulting in graft-versus-host disease, disturbing a favorable balance between the graft-versus-leukemia effect and graft-versus-host disease. New therapeutic modalities are, therefore, required to allow early administration of T cells capable of exerting a graft-versus-leukemia effect without causing graft-versus-host disease. Here we describe the isolation of virus-specific T cells using Streptamer-based isolation technology and subsequent transfer of the minor histocompatibility antigen HA-1-specific T-cell receptor using retroviral vectors. Isolation of virus-specific T cells and subsequent transduction with HA-1-T-cell receptor resulted in rapid in vitro generation of highly pure, dual-specific T cells with potent anti-leukemic reactivity. Due to the short production procedure of only 10-14 days and the defined specificity of the T cells, administration of virus-specific T cells transduced with the HA-1-T-cell receptor as early as 8 weeks after allogeneic stem cell transplantation is feasible. (This clinical trial is registered at www.clinicaltrialsregister.eu as EudraCT number 2010-024625-20).

  13. Assessing the adequacy of procedure-specific consent forms in orthopaedic surgery against current methods of operative consent

    PubMed Central

    Barritt, Andrew W; Clark, Laura; Teoh, Victoria; Cohen, Adam MM; Gibb, Paul A

    2010-01-01

    INTRODUCTION This is an audit of patient understanding following their consent for orthopaedic procedures and uses information on new Orthoconsent forms endorsed by the British Orthopaedic Association as the set standard. The objectives were to: (i) assess whether patients& understanding of knee arthroscopy (KA) and total knee replacement (TKR) at the point of confirming their consent reaches the set standard; and (ii) to ascertain whether issuing procedure-specific Orthoconsent forms to patients can improve this understanding. SUBJECTS AND METHODS This was a prospective audit using questionnaires consisting of 26 (for KA) or 35 (for TKR) questions based on the appropriate Orthoconsent form in a department of orthopaedic surgery within a UK hospital. Participants were 100 patients undergoing KA and 60 patients undergoing TKR between February and July 2008. Participants were identified from sequential operating lists and all had capacity to give consent. During the first audit cycle, consent was discussed with the patient and documented on standard yellow NHS Trust approved generic consent forms. During the second audit cycle, patients were additionally supplied with the appropriate procedure-specific consent form downloaded from which they were required to read at home and sign on the morning of surgery. RESULTS Knee arthroscopy patients consented with only the standard yellow forms scored an average of 56.7%, rising to 80.5% with use of Orthoconsent forms. Similarly, total knee replacement patients& averages rose from 57.6% to 81.6%. CONCLUSIONS Providing patients with an Orthoconsent form significantly improves knowledge of their planned procedure as well as constituting a more robust means of information provision and consent documentation. PMID:20412675

  14. Toward a consolidation of the CPV-specific-test procedures for inverters

    NASA Astrophysics Data System (ADS)

    Voarino, Philippe; Dominguez, César; Bier, Anthony; Roujol, Yannick; Mangeant, Christophe; Baudrit, Mathieu

    2015-09-01

    The inverter in a photovoltaic system assures two essential functions. The first is to track the maximum power point of the system IV curve throughout variable environmental conditions. The second is to convert DC power delivered by the PV panels into AC power. Nowadays, in order to qualify inverters, manufacturers and certifying organisms use mainly European and/or CEC efficiency standards. The question arises if these are still representative of CPV system behaviour. We propose to use a set of CPV - specific weighted average and a representative dynamic response to have a better determination of the static and dynamic MPPT efficiencies. Four string-sized commercial inverters used in real CPV plants have been tested.

  15. Curtailing patient-specific IMRT QA procedures from 2D dose error distribution.

    PubMed

    Kurosu, Keita; Sumida, Iori; Mizuno, Hirokazu; Otani, Yuki; Oda, Michio; Isohashi, Fumiaki; Seo, Yuji; Suzuki, Osamu; Ogawa, Kazuhiko

    2016-06-01

    A patient-specific quality assurance (QA) test is conducted to verify the accuracy of dose delivery. It generally consists of three verification processes: the absolute point dose difference, the planar dose differences at each gantry angle, and the planar dose differences by 3D composite irradiation. However, this imposes a substantial workload on medical physicists. The objective of this study was to determine whether our novel method that predicts the 3D delivered dose allows certain patient-specific IMRT QAs to be curtailed. The object was IMRT QA for the pelvic region with regard to point dose and composite planar dose differences. We compared measured doses, doses calculated in the treatment planning system, and doses predicted by in-house software. The 3D predicted dose was reconstructed from the per-field measurement by incorporating the relative dose error distribution into the original dose grid of each beam. All point dose differences between the measured and the calculated dose were within ±3%, whereas 93.3% of them between the predicted and the calculated dose were within ±3%. As for planar dose differences, the gamma passing rates between the calculated and the predicted dose were higher than those between the calculated and the measured dose. Comparison and statistical analysis revealed a correlation between the predicted and the measured dose with regard to both point dose and planar dose differences. We concluded that the prediction-based approach is an accurate substitute for the conventional measurement-based approach in IMRT QA for the pelvic region. Our novel approach will help medical physicists save time on IMRT QA.

  16. Curtailing patient-specific IMRT QA procedures from 2D dose error distribution

    PubMed Central

    Kurosu, Keita; Sumida, Iori; Mizuno, Hirokazu; Otani, Yuki; Oda, Michio; Isohashi, Fumiaki; Seo, Yuji; Suzuki, Osamu; Ogawa, Kazuhiko

    2016-01-01

    A patient-specific quality assurance (QA) test is conducted to verify the accuracy of dose delivery. It generally consists of three verification processes: the absolute point dose difference, the planar dose differences at each gantry angle, and the planar dose differences by 3D composite irradiation. However, this imposes a substantial workload on medical physicists. The objective of this study was to determine whether our novel method that predicts the 3D delivered dose allows certain patient-specific IMRT QAs to be curtailed. The object was IMRT QA for the pelvic region with regard to point dose and composite planar dose differences. We compared measured doses, doses calculated in the treatment planning system, and doses predicted by in-house software. The 3D predicted dose was reconstructed from the per-field measurement by incorporating the relative dose error distribution into the original dose grid of each beam. All point dose differences between the measured and the calculated dose were within ±3%, whereas 93.3% of them between the predicted and the calculated dose were within ±3%. As for planar dose differences, the gamma passing rates between the calculated and the predicted dose were higher than those between the calculated and the measured dose. Comparison and statistical analysis revealed a correlation between the predicted and the measured dose with regard to both point dose and planar dose differences. We concluded that the prediction-based approach is an accurate substitute for the conventional measurement-based approach in IMRT QA for the pelvic region. Our novel approach will help medical physicists save time on IMRT QA. PMID:26661854

  17. European Union regulators and industry agree on improving specific environmental release categories: Report from the exchange network for exposure scenarios specific environmental release category workshop on May 13, 2016.

    PubMed

    Ahrens, Andreas; Moilanen, Marianne; Martin, Sara; Garcia-John, Enrique; Sättler, Daniel; Bakker, Joost; Reihlen, Antonia; Wind, Thorsten; Tolls, Johannes

    2017-09-01

    Specific environmental release categories (SPERCs) are an instrument for lower-tier environmental emissions assessments. They support chemical safety assessments under the European Union (EU) regulation Registration, Evaluation, Authorisation, and Restriction of Chemicals. SPERCs have been developed by industry and subjected to regulatory review. Within the framework of the Chemical Safety Report/Exposure Scenario Roadmap, the EU Chemicals Agency (ECHA), the EU Member State authorities, and European industry sector associations collaborate to improve the quality of the SPERCs. Following up on the outcome of ECHA's SPERC Best Practice Project, industry, together with ECHA, developed an updated SPERC factsheet template and guidance on how to fill it out. In addition, industry developed 2 sets of SPERC factsheet examples and the corresponding SPERC background documents. These documents were submitted to a multistakeholder review process. The comments from the review were discussed at a workshop in spring 2016. The workshop participants acknowledged the revised factsheet format including the corresponding guidance, the 2 SPERC factsheets, and the 2 SPERC background documents as best practice examples. The package is expected to support further improvement of the quality of the SPERCs. A common understanding was achieved of the need to match the level of detail of the use conditions description with the risk to be controlled (i.e., the emission intensity and hazard profile of the substances) and with the level of conservatism of SPERC release factors. The complete and transparent documentation of the derivation of the release factors and of their conservatism is conceived as crucial for the credibility of the SPERCs, such that they can be trusted by partners in the chemicals supply chain and by regulators. To that end, background documents will include a dedicated section describing the conservatism of SPERCs. The workshop concluded with an outline of the practical way

  18. Graphical procedures for evaluating overall and subject-specific incremental values from new predictors with censored event time data.

    PubMed

    Uno, Hajime; Cai, Tianxi; Tian, Lu; Wei, L J

    2011-12-01

    Quantitative procedures for evaluating added values from new markers over a conventional risk scoring system for predicting event rates at specific time points have been extensively studied. However, a single summary statistic, for example, the area under the receiver operating characteristic curve or its derivatives, may not provide a clear picture about the relationship between the conventional and the new risk scoring systems. When there are no censored event time observations in the data, two simple scatterplots with individual conventional and new scores for "cases" and "controls" provide valuable information regarding the overall and the subject-specific level incremental values from the new markers. Unfortunately, in the presence of censoring, it is not clear how to construct such plots. In this article, we propose a nonparametric estimation procedure for the distributions of the differences between two risk scores conditional on the conventional score. The resulting quantile curves of these differences over the subject-specific conventional score provide extra information about the overall added value from the new marker. They also help us to identify a subgroup of future subjects who need the new predictors, especially when there is no unified utility function available for cost-risk-benefit decision making. The procedure is illustrated with two data sets. The first is from a well-known Mayo Clinic primary biliary cirrhosis liver study. The second is from a recent breast cancer study on evaluating the added value from a gene score, which is relatively expensive to measure compared with the routinely used clinical biomarkers for predicting the patient's survival after surgery. © 2011, The International Biometric Society.

  19. Procedure-specific Cardiac Surgeon Volume associated with Patient outcome following Valve Surgery, but not Isolated CABG Surgery.

    PubMed

    Ch'ng, Stephanie L; Cochrane, Andrew D; Wolfe, Rory; Reid, Christopher; Smith, Catherine I; Smith, Julian A

    2015-06-01

    Trends towards surgical sub-specialisation to improve patient-outcomes are well-documented and largely supported by evidence. However few studies have examined whether this benefit exists within adult-cardiac surgery. To answer whether sub-specialisation within adult-cardiac surgery improves patient-outcomes, this study assessed the relationship between procedure-specific and total-cardiac surgeon-volume and mortality and morbidity in cardiac-valve and coronary artery bypass grafting (CABG) surgery. Data came from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registry from 2001 to 2010 and included 23 hospitals, 109 surgeons, 20,619 patients with isolated-CABG-surgery and 11,536 patients with a valve-procedure. Hierarchical logistic regression using generalised estimating equations was used to analyse outcomes. Measures included operative-mortality and occurrence of a complication (deep sternal wound infection, new stroke, acute kidney injury). Crude operative mortality (and complication rates) were 1.7% (4.9%) and 4% (11%) in the isolated-CABG and valve-surgical populations respectively. A greater procedure-specific surgeon volume was associated with reduced mortality and complication rates in valve-surgery but not isolated-CABG. There was a 33% decrease in odds of dying for every additional 50 valve procedures performed [OR 0.67, p=0.003]. Conversely, greater total-cardiac surgical volume for individual surgeons did not result in improved outcomes, for both isolated-CABG and valve populations. Our finding of an association between increased valve-specific surgeon volumes with improved valve-surgery outcomes, and absence of an association between these outcomes and annual total-cardiac surgical experience supports the case for sub-specialisation specifically within the field of valve surgery. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and

  20. Simple procedure for the synthesis of high specific activity tritiated (6S)-5-formyltetrahydrofolate

    SciTech Connect

    Moran, R.G.; Colman, P.D.

    1982-05-01

    The 5-position of tetrahydrofolate was found to be unusually reactive with low concentrations of formic acid in the presence of a water-soluble carbodiimide. The product of this reaction has neutral and acid ultraviolet spectra and chromatographic behavior consistent with its identity as 5-formyltetrahydrofolate (leucovoriun). When enzymatically synthesized (6S)-tetrahydrofolate was used as starting material, the product supported the growth of folate-depleted L1210 cells at one-half the concentration required for authentic (6R,S)-leucovorin. This reaction has been used to produce high specific activity (44 Ci/mmol) (/sup 3/H)(6S)-5-formyltetrahydrofolate in high yield. Experiments with (/sup 14/C)formic acid indicate that 1 mol of formate reacted per mol of tetrahydrofolate but that no reaction occurred with a variety of other folate compounds. (6S)-5-Formyltetrahydrofolate, labeled in the formyl group with /sup 14/C, has also been synthesized using this reaction. These easily produced, labeled folates should allow close examination of the transport and utilization of leucovorin and of the mechanism of reversal of methotrexate toxicity by reduced folate cofactors.

  1. CMV specific cytokine release assay in whole blood is optimized by combining synthetic CMV peptides and toll like receptor agonists.

    PubMed

    Dammermann, Werner; Bochmann, David; Bentzien, Frank; Komorowski, Lars; Steinhagen, Katja; Ullrich, Sebastian; van Lunzen, Jan; Lüth, Stefan

    2014-12-01

    Interferon gamma release assays (IGRAs) are widely used to detect pathogen specific cellular immunity. Cytomegalovirus (CMV) is the foremost problematic viral infection in immunocompromised patients such as transplant or HIV infected patients. CMV antibody ELISAs are not able to predict CMV specific cellular immunity during immunosuppression. We developed a CMV specific IGRA comparing synthetic CMV peptides, native lysate and recombinant antigen. In addition, TLR agonists were tested to enhance CMV antigen immunogenicity. 397 healthy controls (HC) were stratified according to CMV IgM and IgG serostatus and subsequently tested for IFNγ- and IL2-secretion in whole blood after challenge with synthetic, native or recombinant CMV antigens and TLR agonists by ELISA. The selected TLR agonists were lipopolysaccharide (LPS), lipoteichoic acid (LTA), peptidoglycan (PGN), zymosan (Zym), polyinosinic-polycytidylic acid (Poly(I:C)), flagellin (Fla), R848, loxoribine (Lox) and bropirimine (Bro). Synthetic pp65 peptides elicited strong IFNγ responses in CMV seropositive, but not seronegative HC (6418 vs. 13 pg/ml). Native lysates and recombinant pp65 induced equally high IFNγ responses in seropositive (35,877 and 26,428 pg/ml) and increased background IFNγ expression in seronegative HC (43 and 1148 pg/ml). Diagnostic sensitivity and specificity with regard to anti-CMV serology reached 100% for synthetic pp65 and native CMV lysate, but 57% and 100% for recombinant pp65, respectively. TLR agonists LTA and Poly(I:C) augmented IFNγ responses after challenge with synthetic pp65 peptide, native lysate or recombinant pp65 in seropositive HC. Seronegative HC remained unaffected. IL2 production was negligible compared to IFNγ. IGRAs using synthetic CMV peptides or native lysate showed the best cytokine signal to noise ratio compared to recombinant antigen and TLR agonists LTA and Poly(I:C) constitute potential costimulating reagents. Copyright © 2014 Elsevier B.V. All rights

  2. Formalising multidisciplinary peer review: developing a haematological malignancy-specific electronic proforma and standard operating procedure to facilitate procedural efficiency and evidence-based clinical practice.

    PubMed

    Trotman, Judith; Trinh, Jimmy; Kwan, Yiu Lam; Estell, Jane A; Fletcher, Julie; Archer, Kate; Lee, Kenneth; Foo, Kerwin; Curnow, Jennifer; Bianchi, Alessandra; Wignall, Lynda; Verner, Emma; Gasiorowski, Robin; Siedlecka, Elizabeth; Cunningham, Ilona

    2017-05-01

    Multidisciplinary team (MDT) meetings aimed at facilitating peer review have become standard practice in oncology. However, there is scant literature on the optimal structure and conduct of such meetings. To develop a process for formal peer review of patients with haematological malignancies and to audit any resulting changes made to the management recommendations of the treating physician. A standard operating procedure (SOP) for MDT meetings was developed essentially to integrate clinical peer review with weekly pathology and radiology meetings. The centrepiece is the electronic submission of a patient-specific proforma (Microsoft InfoPath) prior to the meeting. It serves as the template for presentation, discussion and recording of recommendations and conclusions. The final verified document is stored in the electronic patient record, and a copy is sent to the general practitioner. The proposed management plans were compared to the consensus recommendations of the meeting for the first 4 years since inception. Both SOP and proforma underwent continual improvements. These provided the framework for the conduct of a robust weekly MDT meeting for peer review of the management of patients with haematological malignancies. On 20% of occasions, patient management plans were altered to optimise patient care as a direct consequence on peer review at the MDT. Our streamlined process, in its ultimate format, has provided a mature and efficient forum for formal peer review in a genuine multidisciplinary environment. Both initial data and informal feedback support its ongoing activity as an integral component of delivering quality patient care. © 2016 Royal Australasian College of Physicians.

  3. Reliability of procedures used in the physical examination of non-specific low back pain: a systematic review.

    PubMed

    May, Stephen; Littlewood, Chris; Bishop, Annette

    2006-01-01

    The purpose of this systematic review was to determine the quality of the research and to assess the reliability of different types of physical examination procedures used in the assessment of patients with non-specific low back pain. A search of electronic databases (MEDLINE, PEDro, AMED, EMBASE, Cochrane, and CINAHL) up to August 2005 identified 48 relevant studies which were analysed for quality and reliability. Pre-established criteria were used to judge the quality of the studies and satisfactory reliability, and conclusions emphasised high quality studies (> or = 60% methods score). The mean quality score of the studies was 52% (range 0 to 88%), indicating weak to moderate methodology. Based on the upper threshold used (kappa/ICC > 0.85) most procedures demonstrated either conflicting evidence or moderate to strong evidence of low reliability. When the lower threshold was used (kappa/ICC > 0.70) evidence about pain response to repeated movements changed from contradictory to moderate evidence for high reliability. Most procedures commonly used by clinicians in the examination of patients with back pain demonstrate low reliability.

  4. Generation and functional analysis of T cell lines and clones specific for schistosomula released products (SRP-A).

    PubMed Central

    Damonneville, M; Velge, F; Verwaerde, C; Pestel, J; Auriault, C; Capron, A

    1987-01-01

    Antigens present in the products released by the larval stage of schistosome (SRP-A) were shown to induce a strong cytotoxic and protective IgE response both in the rat and the monkey. T cell lines and clones specific for SRP-A or 26 kD antigens which are the main target of the cytotoxic IgE have been derived. The passive transfer of SRP-A specific T lymphocytes into infected rats led to an increase of the IgE response, conferring a significant level of protection to the rats. In coculture assays in vitro, these cell lines significantly enhanced the production of IgE by SRP-A sensitized rat spleen cells. This helper effect on the IgE response was confirmed with 26 kD T cell clone supernatants. Moreover, supernatants obtained after stimulation with phorbol myristate acetate were able to enhance the IgE production of a hybridoma B cell line (B48-14) producing a monoclonal IgE antibody, cytotoxic for the schistosomula. PMID:3498590

  5. Codon-reading specificities of mitochondrial release factors and translation termination at non-standard stop codons

    NASA Astrophysics Data System (ADS)

    Lind, Christoffer; Sund, Johan; Åqvist, Johan

    2013-12-01

    A key feature of mitochondrial translation is the reduced number of transfer RNAs and reassignment of codons. For human mitochondria, a major unresolved problem is how the set of stop codons are decoded by the release factors mtRF1a and mtRF1. Here we present three-dimensional structural models of human mtRF1a and mtRF1 based on their homology to bacterial RF1 in the codon recognition domain, and the strong conservation between mitochondrial and bacterial ribosomal RNA in the decoding region. Sequence changes in the less homologous mtRF1 appear to be correlated with specific features of the mitochondrial rRNA. Extensive computer simulations of the complexes with the ribosomal decoding site show that both mitochondrial factors have similar specificities and that neither reads the putative vertebrate stop codons AGA and AGG. Instead, we present a structural model for a mechanism by which the ICT1 protein causes termination by sensing the presence of these codons in the A-site of stalled ribosomes.

  6. Resources and procedures in the treatment of heavy menstrual bleeding with the levonorgestrel-releasing intrauterine system (LNG-IUS) or hysterectomy in Brazil.

    PubMed

    Bahamondes, M Valeria; de Lima, Yuri; Teich, Vanessa; Bahamondes, Luis; Monteiro, Ilza

    2012-09-01

    Heavy menstrual bleeding (HMB) is the most common complaint of women seeking gynecological care. Treatments included surgical or medical options including hysterectomy and the levonorgestrel-releasing intrauterine system (LNG-IUS) due to the profound suppression of endometrial growth that intrauterine LNG exerts which results in amenorrhea or in a reduction of blood loss. The study was conducted to evaluate the resources and procedures involved in inserting an LNG-IUS compared to performing hysterectomy in women with HMB in a public sector hospital in Brazil. Two cohorts of women were studied: women who accepted an LNG-IUS (n=124) and matched women who underwent hysterectomy on the same day (n=122). We evaluate the number of procedures carried out in each group of women, including those performed before the decision was made to insert an LNG-IUS or to perform hysterectomy, the insertion of the device itself and the surgical procedure, in addition to the procedures and complications registered up to 1 year after LNG-IUS insertion or hysterectomy. Age and the duration of HMB were significantly lower in the LNG-IUS acceptors than women at the hysterectomy group. The numbers of gynecological consultations and Pap smears were similar in both groups; however, women in the hysterectomy group also underwent laboratory tests, ultrasonography, chest X-ray and electrocardiogram. In the hysterectomy group, the main complications were hemorrhage (six), bladder/bowel perforation (four), complications with anesthesia (one), ureteral reimplantation required (one) and abdominal pain (two). At 1 year, HMB was controlled in 83.1% of women in the LNG-IUS group, and 106 women continued with the device. Both treatments were effective in HMB control. Fewer resources and complications were observed in LNG-IUS acceptors when compared to hysterectomy. The LNG-IUS represents a good strategy for reducing the number of hysterectomies and the resources required for women with HMB. Copyright

  7. Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses

    PubMed Central

    Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W. R.; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

    2015-01-01

    Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to

  8. Association of Otolaryngology Resident Duty Hour Restrictions With Procedure-Specific Outcomes in Head and Neck Endocrine Surgery.

    PubMed

    Smith, Aaron; Braden, Lauren; Wan, Jim; Sebelik, Merry

    2017-06-01

    Graduate medical education has undergone a transformation from traditional long work hours to a restricted plan to allow adequate rest for residents. The initial goal of this restriction is to improve patient outcomes. To determine whether duty hour restrictions had any impact on surgery-specific outcomes by analyzing complications following thyroid and parathyroid procedures performed before and after duty hour reform. Retrospective cross-sectional analysis of the National Inpatient Sample (NIS).The NIS was queried for procedure codes associated with thyroid and parathyroid procedures for the years 2000 to 2002 and 2006 to 2008. Hospitals were divided based on teaching status into 3 groups: nonteaching hospitals (NTHs), teaching hospitals without otolaryngology programs (THs), and teaching hospitals with otolaryngology programs (THs-OTO). Procedure-specific complication rates, length of stay, and mortality rates were collected. SAS statistical software (version 9.4) was used for analysis with adjustment using Charlson comorbidity index. Total numbers of head and neck endocrine procedures were 34 685 and 39 770 (a 14.7% increase), for 2000 to 2002 and 2006 to 2008, respectively. THs-OTO contributed a greater share of procedures in 2006 to 2008 (from 18% to 25%). With the earlier period serving as the reference, length of stay remained constant (2.1 days); however, total hospital charges increased (from $12 978 to $23 708; P < .001). Rates of postoperative hematoma (odds ratio [OR], 1.21; 95% CI, 1.06-1.38), hypoparathyroidism (OR, 1.27; 95% CI, 1.06-1.52), and unintentional vessel lacerations (OR, 1.36; 95% CI, 1.02-1.83) increased overall with NTHs (OR, 1.26; 95% CI, 1.04-1.52), THs (OR, 1.65; 95% CI, 1.15-2.37), and THs-OTO (OR, 1.98; 95% CI, 1.09-3.61) accounting for these differences, respectively. Overall mortality decreased (OR, 0.66; 95% CI, 0.47-0.94) following a decrease in the TH-OTO mortality rate (OR, 0.34; 95% CI, 0.12-0.93). While

  9. Dual-portal endoscopic release of the transverse ligament in carpal tunnel syndrome: results of 411 procedures with special reference to technique, efficacy, and complications.

    PubMed

    Oertel, Joachim; Schroeder, Henry W S; Gaab, Michael R

    2006-08-01

    Endoscopic release of carpal tunnel syndrome is still under debate. The main advantages of the technique are considered to be minor postoperative pain and a more rapid postoperative recovery. Disadvantages are thought to be the impossibility of a direct median nerve neurolysis and a higher surgical complication rate, including injury to the median nerve. The results of 411 consecutive endoscopic carpal tunnel procedures performed between March 1995 and September 2004 are presented. All patients were prospectively followed. In the present series, a success rate of 98.05% was observed. There was no permanent morbidity and, in particular, there was no injury of the median nerve. In four (0.97%) patients, the preoperative symptoms did not improve. In two (0.49%) of these patients, an incomplete release of the carpal ligament occurred. In another four patients (0.97%), a switch to open surgery was required. The present data prove that the endoscopic technique is a safe and reliable technique for carpal tunnel surgery. The data do not support the current discussion of a higher risk of median nerve injury with endoscopic carpal tunnel surgery. Thus, for our group, the endoscopic technique represents the therapy of choice for the primary idiopathic carpal tunnel syndrome.

  10. 46 CFR 160.062-6 - Procedure for approval.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Releases. Lifesaving Equipment, Hydraulic and Manual § 160.062-6 Procedure for approval. General. Hydraulic releases for use on lifesaving equipment for merchant vessels are approved only by the Commandant, U.S. Coast Guard. In order to be approved, the hydraulic releases must...

  11. 46 CFR 160.062-6 - Procedure for approval.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Releases. Lifesaving Equipment, Hydraulic and Manual § 160.062-6 Procedure for approval. General. Hydraulic releases for use on lifesaving equipment for merchant vessels are approved only by the Commandant, U.S. Coast Guard. In order to be approved, the hydraulic releases must...

  12. 46 CFR 160.062-6 - Procedure for approval.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Releases. Lifesaving Equipment, Hydraulic and Manual § 160.062-6 Procedure for approval. General. Hydraulic releases for use on lifesaving equipment for merchant vessels are approved only by the Commandant, U.S. Coast Guard. In order to be approved, the hydraulic releases must...

  13. 46 CFR 160.062-6 - Procedure for approval.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Releases. Lifesaving Equipment, Hydraulic and Manual § 160.062-6 Procedure for approval. General. Hydraulic releases for use on lifesaving equipment for merchant vessels are approved only by the Commandant, U.S. Coast Guard. In order to be approved, the hydraulic releases must...

  14. Copper retention, calcium release and ultrastructural evidence indicate specific Cuprolinic Blue uptake and peculiar modifications in mineralizing aortic valves.

    PubMed

    Ortolani, F; Tubaro, F; Petrelli, L; Gandaglia, A; Spina, M; Marchini, M

    2002-01-01

    Previously, reactions with copper phthalocyanines at 0.05 M critical electrolyte concentration were found to cause demineralization in calcifying porcine aortic valves after subdermal implantation in rat, as well as simultaneous visualization of peculiar phthalocyanine-positive layers around cells and cell-derived matrix vesicles. In the present investigation, an appraisal was made of the mechanism and specificity of reactions with Cuprolinic Blue by comparing quantitatively calcium release and copper retention by calcified aortic valves reacted with this phthalocyanine under different critical electrolyte concentration conditions, and the corresponding ultrastructural patterns. It was found that (i) decalcifying properties are inversely proportional to salt molarity; (ii) reactivity to Cuprolinic Blue is critical electrolyte concentration-dependent, since the greatest copper retention occurred in 0.05 M critical electrolyte concentration Cuprolinic Blue-reacted samples, the only ones that also exhibited phthalocyanine-positive layers; (iii) the appearance of phthalocyanine-positive layers depends on Cuprolinic Blue uptake, revealing pericellular clustering of calcium-binding, anionic molecules; and (iv) minor Cuprolinic Blue uptake occurs by residual proteoglycans which still remain in the extracellular matrix after 6-week-long subdermal implantation. The present results indicate that this method is appropriate for the study of mineralized tissues and illustrate peculiar tissue modifications occurring at least in the experimental conditions used here.

  15. Specific Association of Growth-associated Protein 43 with Calcium Release Units in Skeletal Muscles of Lower Vertebrates

    PubMed Central

    Caprara, G.A.; Perni, S.; Morabito, C.; Mariggiò, M.A.; Guarnieri, S.

    2014-01-01

    Growth-associated protein 43 (GAP43), is a strictly conserved protein among vertebrates implicated in neuronal development and neurite branching. Since GAP43 structure contains a calmodulin-binding domain, this protein is able to bind calmodulin and gather it nearby membrane network, thus regulating cytosolic calcium and consequently calcium-dependent intracellular events. Even if for many years GAP43 has been considered a neuronal-specific protein, evidence from different laboratories described its presence in myoblasts, myotubes and adult skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized between calcium release units (CRUs) and mitochondria in mammalian skeletal muscle suggesting that, also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis. However, the previous studies could not clearly distinguish between a mitochondrion- or a triad-related positioning of GAP43. To solve this question, the expression and localization of GAP43 was studied in skeletal muscle of Xenopus and Zebrafish known to have triads located at the level of the Z-lines and mitochondria not closely associated with them. Western blotting and immunostaining experiments revealed the expression of GAP43 also in skeletal muscle of lower vertebrates (like amphibians and fishes), and that the protein is localized closely to the triad junction. Once more, these results and GAP43 structural features, support an involvement of the protein in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species. PMID:25578978

  16. Simple dual-spotting procedure enhances nLC-MALDI MS/MS analysis of digests with less specific enzymes.

    PubMed

    Baeumlisberger, Dominic; Rohmer, Marion; Arrey, Tabiwang N; Mueller, Benjamin F; Beckhaus, Tobias; Bahr, Ute; Barka, Guenes; Karas, Michael

    2011-06-03

    The beneficial effect of high mass accuracy in mass spectrometry is especially pronounced when using less specific enzymes as the number of theoretically possible peptides increases dramatically without any cleavage specificity defined. Together with a preceding chromatographic separation, high-resolution mass spectrometers such as the MALDI-LTQ-Orbitrap are therefore well suited for the analysis of protein digests with less specific enzymes. A combination with fast, automated, and informative MALDI-TOF/TOF analysis has already been shown to yield increased total peptide and protein identifications. Here, a simple method for nLC separation and subsequent alternating spotting on two targets for both a MALDI-LTQ-Orbitrap and a MALDI-TOF/TOF instrument is introduced. This allows for simultaneous measurements on both instruments and subsequent combination of both data sets by an in-house written software tool. The performance of this procedure was evaluated using a mixture of four standard proteins digested with elastase. Three replicate runs were examined concerning repeatability and the total information received from both instruments. A cytosolic extract of C. glutamicum was used to demonstrate the applicability to more complex samples. Database search results showed that an additional 32.3% of identified peptides were found using combined data sets in comparison to MALDI-TOF/TOF data sets.

  17. Serum concentrations of prostate-specific antigen after diagnostic procedures and transurethral microwave thermotherapy of benign prostatic hyperplasia.

    PubMed

    Daehlin, L; Frugård, J; Farstad, M

    1996-05-01

    The objective was to study the effects of diagnostic and therapeutic procedures on serum prostate-specific antigen (PSA) concentration. Urethrocystoscopy in combination with digital rectal examination was followed by a moderate increase of serum PSA for 7-10 days. At 1 day after transurethral microwave thermotherapy (TUMT), an acute and pronounced effect on PSA was observed, which returned to baseline level after 4 weeks. The initial rise in serum PSA corresponded to a PSA density of 1.11, compared to 0.07 at baseline. The present data should be taken into consideration in conjunction with endoscopic evaluation of the lower urinary tract. Additionally, the acute effect on PSA after TUMT strongly suggests the ability of thermotherapy to induce cellular injury and death. One-year follow-up, however, was associated with increased PSA levels, indicating that only a minor part of the PSA-producing compartment was lost in the acute phase.

  18. A Modeling Procedure by Means of Multicriteria Analysis: Application in the Case of Specific Surface Estimation of Anodized Aluminium

    NASA Astrophysics Data System (ADS)

    Fotilas, Panayiotis; Batzias, Athanasios F.

    2009-08-01

    A methodological framework designed/developed under the form of an algorithmic procedure (including 20 activity stages and 10 decision nodes) has been applied for multicriteria ranking of models. The criteria used are: fitting to experimental data, agreement with theoretical aspects, model simplicity, experimental falsifiability, progressiveness, and relation to other ISs, as proved by a common path/rationale of deduction. An implementation is presented referring to the selection of pore ideal structure of anodized aluminium among the alternatives: cylindrical (A1), truncated-cone-like (A2), trumpet-like (A3), vesica-like (A4), multiple-base (A5), and tilted-cylinder-like (A6). The alternative A2 (implying corresponding specific surface estimation of the anodic film) was ranked first and the solution was proved to be robust.

  19. A morphologic and semi-quantitative technique to analyze synthesis and release of specific proteins in cells.

    PubMed

    Huang, Guowei; Wang, Yun; Wang, Juping; Yang, Chunzhang; Huang, Tao; Zhuang, Zhengping; Gu, Jiang

    2014-12-05

    With the rapid advancement of cell biology, the evaluation of a given protein's synthesis and release in cells becomes critical. However, up to now there has been no technique available to morphologically visualize and measure a newly synthesized protein in cells, nor can we measure the protein's release from the cells. In this study, we developed a set of assays combining pulse chase amino acid substitution, non-radioactive labeling, and immunofluorescence co-localization to visualize newly synthesized proteins in individual cells and then to detect their release using modified ELISA. We demonstrated the synthesis and release of Bcl-2, MMP-9, and immunoglobulin G (IgG) in a human trophoblast cell line, of which the last finding has not been reported previously. This new technique offers a powerful tool to evaluate the dynamics of the synthesis and release of target proteins in individual cultured cells with wide applications in genetic and protein analysis.

  20. Preparation and characterization of luteinising-hormone releasing hormone nanoliposomal microbubbles specifically targeting ovarian cancer cells in vitro.

    PubMed

    Zhang, Jinyi; Liu, Sisun; Zhu, Yuanfang; Zhang, Liping; Li, Wenjuan; Wang, Fen; Huang, Shuying

    2014-07-01

    The aim of the present study was to prepare luteinizing-hormone releasing hormone (LHRH) nanoliposomal microbubbles specifically targeting ovarian cancer cells. The lyophilization/sonication method was used to prepare non-targeting nanoliposomal microbubbles (N-N-Mbs). Using the biotin-avidin bridge method, conjugated LHRH antibodies to N-N-Mbs generated LHRH nanoliposomal microbubbles (LHRH-N-Mbs) specifically targeting ovarian cancer cells. The morphology and physicochemical properties of the microbubbles was detected using an optical microscope and zeta detector. The binding affinity between the secondary antibody and LHRH-N-Mbs or N-N-Mbs was determined by flow cytometry. The binding of LHRH-N-Mb to human ovarian cancer cells (OVCAR-3) was detected by light microscopy. The rounded and uniformly distributed N-N-Mbs and LHRH-N-Mbs were successfully generated. The particle size ranged from 295-468 nm with a mean of 360 nm for N-N-Mbs or 369-618 nm with a mean of 508 nm for LHRH-N-Mbs. There was a significant difference in size between the two groups (P<0.05), although the surface potential of the two microbubbles remained the same (-14.6 mV). Following being kept at room temperature for 14 days, no significant difference in the physicochemical properties of the LHRH-N-Mbs was detected compared with that of freshly prepared microbubbles. The secondary antibody binding rate of LHRH-N-Mbs and N-N-Mbs was 75.6 and 0.83%, respectively. Furthermore, the formation of a rosette-like structure surrounding OVCAR-3 cells was observed after the cells were incubated with LHRH-N-Mbs, whereas pre-incubation with LHRH antibody blocked this rosette formation. In conclusion, LHRH-N-Mbs specifically targeting ovarian cancer cells were successfully prepared through biotin-avidin mediation and the lyophilization/sonication method. The key feature of LHRH-N-Mbs is their small size, stability and high efficiency in targeting human OVCAR-3 cells in vitro.

  1. Polymeric drugs with prolonged sustained delivery of specific anti-aggregant agents for platelets: kinetic analysis of the release mechanism.

    PubMed

    Gallardo, Alberto; Rodríguez, Gema; Fernández, Mar; Aguilar, María Rosa; San Román, Julio

    2004-01-01

    The in vitro aqueous behaviour of a metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate (THEMA)/N,N'-dimethylacrylamide (DMA) copolymer with a THEMA molar content of 39% (labeled THDMA39) has been investigated. This composition has been selected to achieve a system able to keep both the non-water solubility during the release and the resorbability (and the water solubility) after the completion of the drug release. This copolymer exhibited, at pH 7.4, a constant release during several months, very interesting for a long term treatments required for the application of some cardiovascular devices. A kinetic model has been developed to explain the pseudo-zero-order kinetics of the release process. This model, which considers (from the aqueous studies) a linear increase with time of the amount of water present in the polymeric matrix, has been able to fit adequately the experimental data.

  2. Product-specific validation of a serological potency test for release of Leptospira vaccines in the European Union.

    PubMed

    Stirling, Catrina; Novokova, Viera

    2013-09-01

    Historically in the European Union, all Leptospira vaccines were released using the European Pharmacopoeia (Ph. Eur.) hamster potency assay. Recently, there has been a shift toward alternatives that offer either refinement of testing or replacement of animals for product release. This is being driven by animal welfare concerns but also by a drive to have more consistent, cheaper, and faster batch release tests. This publication discusses one such example of a multicomponent canine vaccine that includes three Leptospira serovars and has recently been registered in the European Union. The potency release test is a refinement because it uses rabbit serology rather than hamster challenge. This publication covers the principles of the test method, challenges faced during its development and registration, and discussion about benefits and limitations of this method. It concludes with a view of how the use of serology testing could fit into an overall strategy to move to fully in vitro testing by adopting a consistency approach.

  3. Welding procedure specification. Supplement 1. Records of procedure qualification tests. Manual gas tungsten arc (DC) and semiautomatic gas metal arc welding of 6XXX aluminum. [6061 and 6063

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1986-06-01

    Procedure WPS-1009 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for manual gas tungsten arc (DC) and semiautomatic gas metal arc (DC) welding of aluminum alloys 6061 and 6063 (P-23), in thickness range 0.187 to 2,0 inch; filler metal is ER4043 (F-23); shielding gases are helium (GTAW) and argon (GMAW).

  4. Assessing surgical quality: comparison of general and procedure-specific morbidity estimation models for the risk adjustment of pancreaticoduodenectomy outcomes.

    PubMed

    Ansorge, C; Lindström, P; Strömmer, L; Blomberg, J; Lundell, L; Andrén-Sandberg, A; Del Chiaro, M; Segersvärd, R

    2014-09-01

    The use of outcomes to evaluate surgical quality implies the need for detailed risk adjustment. The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) is a generally applicable risk adjustment model suitable for pancreatic surgery. A pancreaticoduodenectomy (PD)-specific intraoperative pancreatic risk assessment (IPRA) estimates the risk of postoperative pancreatic fistula (POPF) and associated morbidity based on factors that are not incorporated into POSSUM. The aim of the study was to compare the risk estimations of POSSUM and IPRA in patients undergoing PD. An observational single-center cohort study was conducted including 195 patients undergoing PD in 2008-2010. POSSUM and IPRA data were recorded prospectively. Incidence and severity of postoperative morbidity was recorded according to established definitions. The cohort was grouped by POSSUM and IPRA risk groups. The estimated and observed outcomes and morbidity profiles of POSSUM and IPRA were scrutinized. POSSUM-estimated risk (62 %) corresponded with observed total morbidity (65 %). Severe morbidity was 17 % and in-hospital-mortality 3.1 %. Individual and grouped POSSUM risk estimates did not reveal associations with incidence (p = 0.637) or severity (p = 0.321) of total morbidity or POPF. The IPRA model identified patients with high POPF risk (p < 0.001), but was even associated with incidence (p < 0.001) and severity (p < 0.001) of total morbidity. The risk factors defined by a PD-specific model were significantly stronger predictive indicators for the incidence and severity of postoperative morbidity than the factors incorporated in POSSUM. If available, reliable procedure-specific risk factors should be utilized in the risk adjustment of surgical outcomes. For pancreatic surgery, generally applicable tools such as POSSUM still have to prove their relevance.

  5. Lexical training through modeling and elicitation procedures with late talkers who have specific language impairment and developmental delays.

    PubMed

    Kouri, Theresa A

    2005-02-01

    Late talkers with specific language impairment and developmental delay make up a large portion of our early childhood caseloads; therefore, an understanding of best clinical practices for these populations is essential. Early lexical learning was examined in 2 interactive treatment approaches with 29 late-talking preschoolers with language and developmental disabilities. Children were randomly assigned to either a mand-elicited imitation (MEI) condition in which elicitations and imitative prompts were used or to a modeling with auditory bombardment (Mod-AB) condition in which auditory bombardment and play modeling were incorporated with no response demands on participants. Lexical production of target vocabulary words already comprehended was measured during a 10-session training period and then during two 50-min play interactions with a parent/caretaker in the home after treatment was completed. Results indicated that the MEI procedure was relatively more effective in facilitating frequency and rate of target word learning in the treatment setting, but no significant differences were found between conditions in the number or percentage of target words generalized to the home setting. Mod-AB children produced more target words that were limited to the home setting than did MEI children, whose productivity was more balanced across settings. Treatment by aptitude regression analyses indicated that none of the preintervention language, cognitive, or total development aptitude scores were predictive of child performance in 1 treatment condition or the other, although Battelle Developmental Inventory communication scores and sizes of preintervention lexicons were predictive of child performance across conditions. Empirical and clinical issues pertaining to the efficacy of modeling- and elicitation-based procedures for late-talking preschoolers are discussed.

  6. Adaptation of the Carrez procedure for the purification of ferulic and p-coumaric acids released from lignocellulosic biomass prior to LC/MS analysis.

    PubMed

    Culhaoglu, Tanya; Zheng, Dan; Méchin, Valérie; Baumberger, Stéphanie

    2011-10-15

    The objective of this study was to adapt and improve an environmentally friendly and fast routine method for the analysis of ferulic and p-coumaric acids released from grass cell-walls by alkaline hydrolysis. This methodological development was performed on maize samples selected for their contrasted contents in ferulic and p-coumaric acids as a consequence of their different maturity stages (from stage of 7th leaf with visible ligule to stage of silage harvest). We demonstrate that the Carrez method is an efficient substitute to the common solvent-consuming extraction by ethyl acetate for the preparation of samples suitable for HPLC-ESI-MS analysis. We prove that it is possible to replace methanol by ethanol in the Carrez step and at last we propose a scale reduction of this procedure that offer a first step towards high throughput determinations. The new method leads to a solvent consumption reduced by a factor 100 and only requires ethanol as organic solvent. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Welding procedure specification. Supplement 1. Records of procedure qualification tests. Gas tungsten arc and low hydrogen shielded metal arc welding of carbon steel

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1986-06-01

    Procedure WPS-128-ASME-1 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and low hydrogen shielded metal arc welding of carbon steels (P-1-1), in thickness range 0.25 to 2.0 inch; filler metals are ER70S-3) (F-6, A-1) (GTAW) and E7018 (F-4, A-1); shielding gas is argon (GTAW).

  8. Welding procedure specification. Supplement 1. Records of procedure qualification tests. Gas tungsten arc and shielded metal arc welding of chromium-nickel steel. [300 series

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1986-06-01

    Procedure WPS-303-ASME-3 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of 300 Series Cr-Ni steels (P-8-1), in thickness range 0.25 to 2.0 inch; filler metals are ER3XX (F-6, A-8) (GTAW) and ER3XX-15 (F-5, A-8); shielding gas for GTAW is argon.

  9. Welding procedure specification: gas tungsten arc and shielded metal arc welding of carbon steel. Supplement 1. Records of procedure qualification tests

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1986-06-01

    Procedure WPS-2103-ASME-1 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of carbon steels (P-1-1) to 300 series Cr-Ni steels (P-8-1), in thickness range 0.25 to 2.0 inch; filler metals are ERNiCr-3 (F-43 (GTAW) and ENiCrFe-3 (F-43) (SMAW); shielding gas is argon (GTAW).

  10. Welding procedure specification. Supplement 1. Records of procedure qualification tests. Gas tungsten arc and shielded metal arc welding of AISI 41XX steels. [4130 and 4142 steels

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.

    1986-06-01

    Procedure WPS-127 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of AISI 4130 and 4142 steels (ASTM A519) (P-No: None), 0.438-inch wall pipe; filler metal is AMS 6457, Class 4130 MC (F-, A-No: None) (GTAW) and E8018-B2L (F-4, A-3) (GMAW): shielding gas is argon (GTAW).

  11. Gas tungsten arc and shielded metal arc welding of carbon steel. Welding procedure specification. Supplement 1. Records of procedure qualification tests

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1986-06-01

    Procedure WPS-104-ASME-2 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of carbon steels (P-1-1), in thickness range 0.25 to 1.0 inch; filler metals are E70S-3 (F-6, A-1) (GTAW) and E6010 (F-3, A-1) (SMAW): shielding gas is argon (GTAW).

  12. Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system.

    PubMed

    Xu, Yongmei; Zhan, Changyou; Fan, Lihong; Wang, Le; Zheng, Hua

    2007-05-24

    Alginate-chitosan (ALG-CS) blend gel beads were prepared based on Ca2+ or dual crosslinking with various proportions of alginate and chitosan. The homogeneous solution of alginate and chitosan was dripped into the solution of calcium chloride; the resultant Ca2+ single crosslinked beads were dipped in the solution of sodium sulfate sequentially to prepare dual crosslinked beads. The dual crosslinkage effectively promoted the stability of beads under gastrointestinal tract conditions. The sustained release profiles of single and dual crosslinked gel beads loaded bovine serum albumin (BSA), a model protein drug, were investigated in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). In SGF, compared to Ca2+ single crosslinked beads, from which BSA released fast and the cumulative drug release percentages were about 80% of all formations in 4 h, the BSA total release from dual crosslinked gel beads was no more than 3% in 8 h. In SIF and SCF, Ca2+ single crosslinked beads were disrupted soon associating with the fast drug release. As to the dual crosslinked beads, the BSA total release from the ALG-CS mass ratio 9:1 (81.24%) was higher than that of 7:3 and 5:5 (less than 60%) in 8 h in SIF; the BSA release from all beads was much faster in SCF than in SIF. The dual crosslinked beads incubated in gastrointestinal tract conditions, the BSA cumulative release of ALG-CS mass ratios 9:1, 7:3 and 5:5 were respectively 2.35, 1.96, 1.76% (in SGF 4 h), 82.86, 78.83, 52.91% (in SIF 3 h) and 97.84, 96.81, 87.26% (in SCF 3 h), which suggested that the dual crosslinked beads have potential small intestine or colon site-specific drug delivery property.

  13. Accurate and Simple Screw Insertion Procedure With Patient-Specific Screw Guide Templates for Posterior C1-C2 Fixation.

    PubMed

    Sugawara, Taku; Higashiyama, Naoki; Kaneyama, Shuichi; Sumi, Masatoshi

    2017-03-15

    Prospective clinical trial of the screw insertion method for posterior C1-C2 fixation utilizing the patient-specific screw guide template technique. To evaluate the efficacy of this method for insertion of C1 lateral mass screws (LMS), C2 pedicle screws (PS), and C2 laminar screws (LS). Posterior C1LMS and C2PS fixation, also known as the Goel-Harms method, can achieve immediate rigid fixation and high fusion rate, but the screw insertion carries the risk of injury to neuronal and vascular structures. Dissection of venous plexus and C2 nerve root to confirm the insertion point of the C1LMS may also cause problems. We have developed an intraoperative screw guiding method using patient-specific laminar templates. Preoperative bone images of computed tomography (CT) were analyzed using three-dimensional (3D)/multiplanar imaging software to plan the trajectories of the screws. Plastic templates with screw guiding structures were created for each lamina using 3D design and printing technology. Three types of templates were made for precise multistep guidance, and all templates were specially designed to fit and lock on the lamina during the procedure. Surgery was performed using this patient-specific screw guide template system, and placement of the screws was postoperatively evaluated using CT. Twelve patients with C1-C2 instability were treated with a total of 48 screws (24 C1LMS, 20 C2PS, 4 C2LS). Intraoperatively, each template was found to exactly fit and lock on the lamina and screw insertion was completed successfully without dissection of the venous plexus and C2 nerve root. Postoperative CT showed no cortical violation by the screws, and mean deviation of the screws from the planned trajectories was 0.70 ± 0.42 mm. The multistep, patient-specific screw guide template system is useful for intraoperative screw navigation in posterior C1-C2 fixation. This simple and economical method can improve the accuracy of screw insertion, and reduce operation time and

  14. Kinetics of a tuberculosis-specific gamma interferon release assay in military personnel with a positive tuberculin skin test.

    PubMed

    van Brummelen, Sigrid E; Bauwens, Anja M; Schlösser, Noël J; Arend, Sandra M

    2010-06-01

    Treatment of latent Mycobacterium tuberculosis infection on the basis of the tuberculin skin test (TST) result is inaccurate due to the false-positive TST results that occur after Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (NTM). Gamma interferon release assays (IGRAs) are based on M. tuberculosis-specific antigens. In a previous study among BCG-naïve military employees, a positive TST result after deployment was mostly associated with a negative IGRA result, suggesting exposure to NTM. Data regarding the kinetics of IGRAs are limited and controversial. The present study aimed to reassess the rate of false-positive TST results and to evaluate the kinetics of the Quantiferon TB Gold In-Tube assay (QFT-Git) in military personnel with a positive TST result. QFT-Git was performed at the time of inclusion in the study and was repeated after 2, 6, 12, and 18 or 24 months. Of 192 participants, 17 were recruits and 175 were screened after deployment (n = 169) or because of travel or health care work. Baseline positive QFT-Git results were observed in 7/17 (41.2%) and 12/174 (6.9%) participants, respectively. During follow-up, a negative QFT-Git result remained negative in 163/165 (98.8%) participants. Of 18 subjects with an initial positive QFT-Git result, reversion to a negative result occurred in 1/6 (16%) recruits, whereas it occurred in 8/12 (66%) subjects after deployment or with other risk factors (P = 0.046). The quantitative result was significantly lower in subjects with reversion than in those with consistent positive results (P = 0.017). This study confirmed a low rate of positive QFT-Git results among military personnel with a positive TST result after deployment, supporting the hypothesis of exposure to NTM. Reversion of the majority of initially low-positive QFT-Git results indicates that QFT-Git may be useful for the diagnosis of later reinfections.

  15. Kinetics of a Tuberculosis-Specific Gamma Interferon Release Assay in Military Personnel with a Positive Tuberculin Skin Test▿ †

    PubMed Central

    van Brummelen, Sigrid E.; Bauwens, Anja M.; Schlösser, Noël J.; Arend, Sandra M.

    2010-01-01

    Treatment of latent Mycobacterium tuberculosis infection on the basis of the tuberculin skin test (TST) result is inaccurate due to the false-positive TST results that occur after Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (NTM). Gamma interferon release assays (IGRAs) are based on M. tuberculosis-specific antigens. In a previous study among BCG-naïve military employees, a positive TST result after deployment was mostly associated with a negative IGRA result, suggesting exposure to NTM. Data regarding the kinetics of IGRAs are limited and controversial. The present study aimed to reassess the rate of false-positive TST results and to evaluate the kinetics of the Quantiferon TB Gold In-Tube assay (QFT-Git) in military personnel with a positive TST result. QFT-Git was performed at the time of inclusion in the study and was repeated after 2, 6, 12, and 18 or 24 months. Of 192 participants, 17 were recruits and 175 were screened after deployment (n = 169) or because of travel or health care work. Baseline positive QFT-Git results were observed in 7/17 (41.2%) and 12/174 (6.9%) participants, respectively. During follow-up, a negative QFT-Git result remained negative in 163/165 (98.8%) participants. Of 18 subjects with an initial positive QFT-Git result, reversion to a negative result occurred in 1/6 (16%) recruits, whereas it occurred in 8/12 (66%) subjects after deployment or with other risk factors (P = 0.046). The quantitative result was significantly lower in subjects with reversion than in those with consistent positive results (P = 0.017). This study confirmed a low rate of positive QFT-Git results among military personnel with a positive TST result after deployment, supporting the hypothesis of exposure to NTM. Reversion of the majority of initially low-positive QFT-Git results indicates that QFT-Git may be useful for the diagnosis of later reinfections. PMID:20375241

  16. Cell type-specific release of matrix-metallo-proteinase-9 by bacterial chemoattractant in human blood phagocytic leukocytes.

    PubMed

    Doerner, Astrid M; Chen, Ling-Yu; Ye, Richard D; Yong, Jiang; Huang, Shuang; Pan, Zhixing K

    2011-01-01

    Stimulation of phagocytic leukocytes with bacterial chemoattractant resulted in the release of matrix metal-loproteinases (MMPs). Little is known about the mechanisms of bacterial chemoattractant regulation of MMP in phagocytic leukocytes. We report here that the mechanisms of the bacterial chemotactic peptidefMLP-induced MMP -9 release in monocytes appeared to be different from fMLP-stimulated MMP-9 release in neutrophils. In freshly prepared peripheral blood monocytes, fMLP induces MMP-9 release, starting at 8 h after stimulation. These functions of fMLP is accompanied by an increase in TNFα expression, and mediated through the phosphorylation of ERK1/2 in monocytes. However, neutrophil preparations that responded to fMLP with MMP-9 release did not require activation of ERK1/2 and TNFα expression. These results suggest a different role of fMLP in MMP-9 expression in neutrophils and monocytes, and the signal molecules involved in mediating this effect in human blood monocytes stimulated by bacterial chemoattractant.

  17. Delay-specific stimuli and genotype interact to determine temporal discounting in a rapid-acquisition procedure.

    PubMed

    Pope, Derek A; Newland, M Christopher; Hutsell, Blake A

    2015-05-01

    The importance of delay discounting to many socially important behavior problems has stimulated investigations of biological and environmental mechanisms responsible for variations in the form of the discount function. The extant experimental research, however, has yielded disparate results, raising important questions regarding Gene X Environment interactions. The present study determined the influence of stimuli that uniquely signal delays to reinforcement on delay discounting in two inbred mouse strains using a rapid-acquisition procedure. BALB/c and C57BL/6 mice responded under a six-component, concurrent-chained schedule in which the terminal-link delays preceding the larger-reinforcer were presented randomly across components of an individual session. Across conditions, components were presented either with or without delay-specific auditory stimuli, i.e., as multiple or mixed schedules. A generalized matching-based model was used to incorporate the impact of current and previous component reinforcer-delay ratios on current component response allocation. Sensitivity to reinforcer magnitude and delay were higher for BALB/c mice, but within-component preference reached final levels faster for C57Bl/6 mice. For BALB/c mice, acquisition of preference across blocks of a component was faster under the multiple than the mixed schedule, but final levels of sensitivity to reinforcement were unaffected by schedule. The speed of acquisition of preference was not different across schedules for C57Bl/6 mice, but sensitivity to reinforcement was higher under the multiple than the mixed schedule. Overall, differences in the acquisition and final form of the discount function were determined by a Gene X Environment interaction, but the presence of delay-specific stimuli attenuated genotype-dependent differences in magnitude and delay sensitivity.

  18. Nanospheres Encapsulating Anti-Leishmanial Drugs for Their Specific Macrophage Targeting, Reduced Toxicity, and Deliberate Intracellular Release

    PubMed Central

    Shukla, Anil Kumar; Patra, Sanjukta

    2012-01-01

    Abstract The current work focuses on the study of polymeric, biodegradable nanoparticles (NPs) for the encapsulation of doxorubicin and mitomycin C (anti-leishmanial drugs), and their efficient delivery to macrophages, the parasite's home. The biodegradable polymer methoxypoly-(ethylene glycol)-b-poly (lactic acid) (MPEG-PLA) was used to prepare polymeric NPs encapsulating doxorubicin and mitomycin C. The morphology, mean diameter, and surface area of spherical NPs were determined by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and BET surface area analysis. X-ray diffraction was performed to validate drug encapsulation. An in vitro release profile of the drugs suggested a fairly slow release. These polymeric NPs were efficiently capable of releasing drug inside macrophages at a slower pace than the free drug, which was monitored by epi-fluorescence microscopy. Encapsulation of doxorubicin and mitomycin C into NPs also decreases cellular toxicity in mouse macrophages (J774.1A). PMID:22925019

  19. Characterization of size-specific particulate matter emission rates for a simulated medical laser procedure--a pilot study.

    PubMed

    Lopez, Ramon; Lacey, Steven E; Lippert, Julia F; Liu, Li C; Esmen, Nurtan A; Conroy, Lorraine M

    2015-05-01

    Prior investigation on medical laser interaction with tissue has suggested device operational parameter settings influence laser generated air contaminant emission, but this has not been systematically explored. A laboratory-based simulated medical laser procedure was designed and pilot tested to determine the effect of laser operational parameters on the size-specific mass emission rate of laser generated particulate matter. Porcine tissue was lased in an emission chamber using two medical laser systems (CO2, λ = 10,600 nm; Ho:YAG, λ = 2100 nm) in a fractional factorial study design by varying three operational parameters (beam diameter, pulse repetition frequency, and power) between two levels (high and low) and the resultant plume was measured using two real-time size-selective particle counters. Particle count concentrations were converted to mass emission rates before an analysis of variance was used to determine the influence of operational parameter settings on size-specific mass emission rate. Particle shape and diameter were described for a limited number of samples by collecting particles on polycarbonate filters, and photographed using a scanning electron microscope (SEM) to examine method of particle formation. An increase in power and decrease in beam diameter led to an increase in mass emission for the Ho:YAG laser at all size ranges. For the CO2 laser, emission rates were dependent on particle size and were not statistically significant for particle ranges between 5 and 10 µm. When any parameter level was increased, emission rate of the smallest particle size range also increased. Beam diameter was the most influential variable for both lasers, and the operational parameters tested explained the most variability at the smallest particle size range. Particle shape was variable and some particles observed by SEM were likely created from mechanical methods. This study provides a foundation for future investigations to better estimate size-specific

  20. Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

    PubMed

    Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

    2015-11-01

    Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs.

  1. Does preoperative abduction value affect functional outcome of combined muscle transfer and release procedures in obstetrical palsy patients with shoulder involvement?

    PubMed Central

    Aydin, Atakan; Ozkan, Turker; Onel, Defne

    2004-01-01

    Background Obstetric palsy is the injury of the brachial plexus during delivery. Although many infants with plexopathy recover with minor or no residual functional deficits, some children don't regain sufficient limb function because of functional limitations, bony deformities and joint contractures. Shoulder is the most frequently affected joint with internal rotation contracture causing limitation of abduction, external rotation. The treatment comprises muscle release procedures such as posterior subscapularis sliding or anterior subscapularis tendon lengtening and muscle transfers to restore the missing external rotation and abduction function. Methods We evaluated whether the preoperative abduction degree affects functional outcome. Between 1998 and 2002, 46 children were operated on to restore shoulder abduction and external rotation. The average age at surgery was 7.6 years and average follow up was 40.8 months. We compared the postoperative results of the patients who had preoperative abduction less than 90° (Group I: n = 37) with the patients who had preoperative abduction greater than 90° (Group II: n = 9), in terms of abduction and external rotation function with angle measurements and Mallet classification. We inquired whether patients in Group I needed another muscle transfer along with latissimus dorsi and teres major transfers. Results In Group I the average abduction improved from 62.5° to 131.4° (a 68.9° ± 22.9°gain) and the average external rotation improved from 21.4° to 82.6° (a 61.1° ± 23°gain). In Group II the average abduction improved from 99.4°to 140°(a40.5° ± 16°gain) and the average external rotation improved from 33.2°to 82.7° (a 49.5° ± 23.9° gain). Although there was a significant difference between Group I and II for preoperative abduction (p = 0.000) and abduction gain in degrees (p = 0.001), the difference between postoperative values of both groups was not significant (p = 0.268). There was also no significant

  2. Procedural learning in Parkinson's disease, specific language impairment, dyslexia, schizophrenia, developmental coordination disorder, and autism spectrum disorders: A second-order meta-analysis.

    PubMed

    Clark, Gillian M; Lum, Jarrad A G

    2017-10-01

    The serial reaction time task (SRTT) has been used to study procedural learning in clinical populations. In this report, second-order meta-analysis was used to investigate whether disorder type moderates performance on the SRTT. Using this approach to quantitatively summarise past research, it was tested whether autism spectrum disorder, developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment differentially affect procedural learning on the SRTT. The main analysis revealed disorder type moderated SRTT performance (p=0.010). This report demonstrates comparable levels of procedural learning impairment in developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment. However, in autism, procedural learning is spared. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

    PubMed

    Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A

    2016-11-01

    The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

  4. Prevention reference manual: chemical specific. Volume 1. Control of accidental releases of hydrogen fluoride (SCAQMD) (South Coast Air Quality Management District). Final report, May 1986-March 1987

    SciTech Connect

    Davis, D.S.; DeWolf, G.B.; Quass, J.D.

    1987-07-01

    This manual summarizes technical information that will assist in identifying and controlling hydrogen fluoride release hazards specific to the South Coast Air Quality Management District (SCAQMD) of southern California. The SCAQMD has considered a strategy for reducing the risk of a major accidental air release of toxic chemicals. The strategy includes monitoring the storage, handling, and use of certain chemicals and provides guidance to industry and communities. Anhydrous hydrogen fluoride, a corrosive liquid that boils at room temperature, rapidly absorbs moisture to form highly corrosive hydrofluoric acid. Hydrogen fluoride gas has an IDLH (immediately dangerous to life and health) concentration of 20 ppm, which makes it a substantial acute toxic hazard. Reducing the risk associated with an accidental release of hydrogen fluoride involves identifying some of the potential causes of accidental releases that apply to the processes that use hydrogen fluoride in the SCAQMD. The manual identifies examples of potential causes as well as measures that may be taken to reduce the accidental-release risk.

  5. Contemporary open partial nephrectomy is associated with diminished procedure-specific morbidity despite increasing technical challenges: a single institutional experience.

    PubMed

    Kava, Bruce R; De Los Santos, Rosely; Ayyathurai, Rajinikanth; Shirodkar, Samir; Manoharan, Murugesan; Leveillee, Raymond; Bird, Vincent; Ciancio, Gaetano; Soloway, Mark S

    2010-08-01

    To review trends in open partial nephrectomy (OPN) at our center, concentrating on patient selection, technique and perioperative complications. A comprehensive database was developed by chart review of consecutive patients undergoing OPN for renal masses at our center. Patient selection, technical modifications, perioperative morbidity, and histopathology were compared in patients undergoing OPN between 1992-1999, 2000-2003, and 2004-2008. Complications were divided into procedure-specific (PSCs) and nonspecific medical complications (NMCs). They were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. One hundred and sixty-three OPNs were performed. Temporal trends identified include: an increase in the mean patient BMI (p = 0.04), an increase in the percentage of patients with central tumors (p < 0.001), decrease in cold ischemia time (p = 0.045), increasing use of a sequential renal vein clamp (p = 0.03), increasing utilization of tissue sealants (p < 0.001), reduced EBL (p = 0.05), reduced length of stay (p = 0.005), and a decline in PSCs from 16 to 7% (p = 0.002). The incidence of histologically benign tumors declined from 34 to 10% (p = 0.001). Thirty-three (20.2%) patients experienced perioperative complications: 70% were CTCAE grade 1 or 2 adverse events. BMI was the only factor that was found to be associated with the risk of complications on multivariate analysis [odds ratio 1.067, CI 95% (1.002-1.136); p = 0.031]. Increasingly, OPN is being utilized for a cohort of challenging patients who are overweight and have centrally located tumors. Despite this, the risk of PSCs is low. Patients who are overweight are at increased risk for perioperative NMCs.

  6. Release-independent depression at pyramidal inputs onto specific cell targets: dual recordings in slices of rat cortex

    PubMed Central

    Thomson, Alex M; Bannister, A Peter

    1999-01-01

    Paired intracellular recordings were performed in slices of adult rat neocortex and hippocampus to examine presynaptic depression. A novel form of depression that occurs even in the absence of transmitter release during conditioning activity was observed at a subset of synaptic connections. In each pair studied, a pyramidal neurone was presynaptic and inputs onto a range of morphologically identified postsynaptic target cells were analysed; high probability connections exhibiting the more traditional forms of release-dependent depression, as well as low probability connections exhibiting facilitation, were tested (n = 35). Connections were tested with presynaptic spike pairs and trains of spikes with a range of interspike intervals. Sweeps in which the first action potential elicited no detectable response (apparent failures of transmission) and sweeps in which the first action potential elicited large EPSPs were selected. Second EPSPs that followed apparent failures were then compared with second EPSPs that followed large first EPSPs. Release-independent depression was apparent when second EPSPs at brief interspike intervals (< 10–15 ms) were on average smaller than second EPSPs at longer interspike intervals, even following apparent failures and when the second EPSP amplitude at these short intervals was independent of the amplitude of the first EPSP. Release-independent depression appeared selectively expressed. Depressing inputs onto some interneurones, such as CA1 basket-like and bistratified cells, and facilitating inputs onto others, such as some fast spiking neocortical interneurones, exhibited this phenomenon. In contrast, depressing inputs onto 10/10 neocortical pyramids and facilitating inputs onto 7/7 oriens-lacunosum moleculare and 5/5 burst firing, sparsely spiny neocortical interneurones did not. PMID:10432339

  7. A procedure for differentiating between the intentional release of biological warfare agents and natural outbreaks of disease: its use in analyzing the tularemia outbreak in Kosovo in 1999 and 2000.

    PubMed

    Grunow, R; Finke, E-J

    2002-08-01

    The events of 11 September and the subsequent anthrax outbreaks in the USA have opened the world's eyes to the threat posed by terrorist groups, criminal organizations and lone operators who will stop at nothing to achieve their goals. The open or covert use of pathogens and toxins as biological warfare agents can no longer be ruled out. Against this background, the appearance of an unusual disease must be studied in order to clarify whether it is a natural or artificially caused occurrence. This issue was recently raised in discussions with local representatives and relief organizations during a tularemia epidemic in Kosovo from October 1999 to May 2000. This paper will present a procedure which attempts to use certain criteria to identify or rule out the use of biological warfare agents in the event of an unusual outbreak of disease. Data and findings gathered by routine epidemiologic and microbiological studies often provide only an indirect answer to this problem. For this reason, various criteria were formulated and points allocated to represent their importance, allowing us to deduce in a semiquantitative manner the degree of possibility of an artificial genesis of outbreaks. The significance and characterization of each criterion are discussed. An analysis of the tularemia epidemic in Kosovo based on the procedure described here indicates that a deliberate release of the causative agent of tularemia, Francisella tularensis, as a biological warfare agent is doubtful. In this paper, an approach is described to discriminate between the intentional use of biological warfare agents and natural outbreaks of infectious diseases. The developed model is flexible and considers the political, military and social analysis of the crisis-afflicted region, the specific features of the pathogen, and the epidemiologic and clinical characteristics of the epidemic.

  8. A Novel Endo-β-N-Acetylglucosaminidase Releases Specific N-Glycans Depending on Different Reaction Conditions

    PubMed Central

    De Moura Bell, Juliana Maria Leite Nobrega; Frese, Steven A.; Liu, Yan; Mills, David A.; Block, David E.; Barile, Daniela

    2015-01-01

    Milk glycoproteins are involved in different functions and contribute to different cellular processes, including adhesion and signaling, and shape the development of the infant micro-biome. Methods have been developed to study the complexities of milk protein glycosylation and understand the role of N-glycans in protein functionality. Endo-β-N-acetylglucosaminidase (EndoBI-1) isolated from Bifidobacterium longum subsp. infantis ATCC 15697 is a recently isolated heat-stable enzyme that cleaves the N-N′-diacetyl chitobiose moiety found in the N-glycan core. The effects of different processing conditions (pH, temperature, reaction time, and enzyme/protein ratio) were evaluated for their ability to change EndoBI-1 activity on bovine colostrum whey glycoproteins using advanced mass spectrometry. This study shows that EndoBI-1 is able to cleave a high diversity of N-glycan structures. Nano-LC-Chip–Q-TOF MS data also revealed that different reaction conditions resulted in different N-glycan compositions released, thus modifying the relative abundance of N-glycan types. In general, more sialylated N-glycans were released at lower temperatures and pH values. These results demonstrated that EndoBI-1 is able to release a wide variety of N-glycans, whose compositions can be selectively manipulated using different processing conditions. PMID:26101185

  9. 43 CFR 11.36 - May the authorized official use both type A and type B procedures for the same release?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the authorized official and/or from population losses; (8) For the type A procedure for coastal and... bordering the provinces in which the population losses occurred. For the type A procedure for Great Lakes... (10) For the type A procedure for Great Lakes environments, lost boating due to closure. (c) If...

  10. Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures

    SciTech Connect

    Rettmann, Maryam E. Holmes, David R.; Camp, Jon J.; Cameron, Bruce M.; Robb, Richard A.; Kwartowitz, David M.; Gunawan, Mia; Johnson, Susan B.; Packer, Douglas L.; Dalegrave, Charles; Kolasa, Mark W.

    2014-02-15

    Purpose: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Methods: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamicin vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. Results: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved

  11. Long-Term Memory: A Review and Meta-Analysis of Studies of Declarative and Procedural Memory in Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Conti-Ramsden, Gina

    2013-01-01

    This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…

  12. Long-Term Memory: A Review and Meta-Analysis of Studies of Declarative and Procedural Memory in Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Conti-Ramsden, Gina

    2013-01-01

    This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…

  13. Evaluation and Specification of Instructional Materials and Management Procedures through Use of a Pupil Performance Profile and a Predictive Model. Final Report.

    ERIC Educational Resources Information Center

    Haring, Norris G.; Berman, Mark L.

    Reported project objectives were to develop a pupil performance profile which describes the effects of specific instructional materials and management procedures on student performance and to develop a model which predicts pupil performance in a given set of materials under particular conditions. Instructional materials (Mathematics, M.W.…

  14. Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors

    PubMed Central

    Dong, Yaqiong; Yang, Jun; Liu, Hongmei; Wang, Tianyou; Tang, Suoqin; Zhang, Jinchao; Zhang, Xin

    2015-01-01

    To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration. PMID:26000060

  15. The olfactory system of migratory adult sea lamprey (Petromyzon marinus) is specifically and acutely sensitive to unique bile acids released by conspecific larvae

    PubMed Central

    1995-01-01

    Larval sea lamprey inhabit freshwater streams and migrate to oceans or lakes to feed after a radical metamorphosis; subsequently, mature adults return to streams to spawn. Previous observations suggested that lamprey utilize the odor of conspecific larvae to select streams for spawning. Here we report biochemical and electrophysiological evidence that this odor is comprised of two unique bile acids released by larvae. High performance liquid chromatography and mass spectrometry demonstrated that larval sea lamprey produce and release two unique bile acids, allocholic acid (ACA) and petromyzonol sulfate (PS). Electro-olfactogram (EOG) recording also demonstrated that the olfactory system of migratory adult sea lamprey is acutely and specifically sensitive to ACA and PS; detection thresholds for these compounds were approximately 10(-12) M. ACA and PS were the most potent of 38 bile acids tested and cross-adaptation experiments suggested that adult sea lamprey have specific olfactory receptor sites associated with independent signal transduction pathways for these bile acids. These receptor sites specifically recognize the key substituents of ACA and PS such as a 5 alpha-hydrogen, three axial hydroxyls, and a C-24 sulfate ester or carboxyl. In conclusion, the unique lamprey bile acids, ACA and PS, are potent and specific stimulants of the adult olfactory system, strongly supporting the hypothesis that these unique bile acids function as migratory pheromones in lamprey. PMID:7658193

  16. Manipulation of flavour and aroma compound sequestration and release using a glycosyltransferase with specificity for terpene alcohols.

    PubMed

    Yauk, Yar-Khing; Ged, Claire; Wang, Mindy Y; Matich, Adam J; Tessarotto, Lydie; Cooney, Janine M; Chervin, Christian; Atkinson, Ross G

    2014-10-01

    Glycosides are an important potential source of aroma and flavour compounds for release as volatiles in flowers and fruit. The production of glycosides is catalysed by UDP-glycosyltransferases (UGTs) that mediate the transfer of an activated nucleotide sugar to acceptor aglycones. A screen of UGTs expressed in kiwifruit (Actinidia deliciosa) identified the gene AdGT4 which was highly expressed in floral tissues and whose expression increased during fruit ripening. Recombinant AdGT4 enzyme glycosylated a range of terpenes and primary alcohols found as glycosides in ripe kiwifruit. Two of the enzyme's preferred alcohol aglycones, hexanol and (Z)-hex-3-enol, contribute strongly to the 'grassy-green' aroma notes of ripe kiwifruit and other fruit including tomato and olive. Transient over-expression of AdGT4 in tobacco leaves showed that enzyme was able to glycosylate geraniol and octan-3-ol in planta whilst transient expression of an RNAi construct in Actinidia eriantha fruit reduced accumulation of a range of terpene glycosides. Stable over-expression of AdGT4 in transgenic petunia resulted in increased sequestration of hexanol and other alcohols in the flowers. Transgenic tomato fruit stably over-expressing AdGT4 showed changes in both the sequestration and release of a range of alcohols including 3-methylbutanol, hexanol and geraniol. Sequestration occurred at all stages of fruit ripening. Ripe fruit sequestering high levels of glycosides were identified as having a less intense, earthier aroma in a sensory trial. These results demonstrate the importance of UGTs in sequestering key volatile compounds in planta and suggest a future approach to enhancing aromas and flavours in flowers and during fruit ripening. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  17. Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

    PubMed Central

    Ladage, Kerstin; Krause-Finkeldey, Dorothee; El Ouardi, Abdessamad; Bitz, Andreas; Streckert, Joachim; Hansen, Volkert; Dermietzel, Rolf

    2011-01-01

    Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded. PMID:21573218

  18. 50 CFR 32.6 - What are the procedures for publication of refuge-specific sport fishing regulations?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... refuge-specific sport fishing regulations? 32.6 Section 32.6 Wildlife and Fisheries UNITED STATES FISH... sport fishing regulations? (a) Refuge-specific fishing regulations are issued only at the time of or after the opening of a wildlife refuge area to sport fishing. (b) Refuge-specific fishing regulations...

  19. 50 CFR 32.6 - What are the procedures for publication of refuge-specific sport fishing regulations?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... comments for consideration at any time. (e) We initially publish refuge-specific sport fishing regulations... refuge-specific sport fishing regulations? 32.6 Section 32.6 Wildlife and Fisheries UNITED STATES FISH... sport fishing regulations? (a) Refuge-specific fishing regulations are issued only at the time of or...

  20. 50 CFR 32.6 - What are the procedures for publication of refuge-specific sport fishing regulations?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... refuge-specific sport fishing regulations? 32.6 Section 32.6 Wildlife and Fisheries UNITED STATES FISH... sport fishing regulations? (a) Refuge-specific fishing regulations are issued only at the time of or after the opening of a wildlife refuge area to sport fishing. (b) Refuge-specific fishing...

  1. 50 CFR 32.6 - What are the procedures for publication of refuge-specific sport fishing regulations?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... refuge-specific sport fishing regulations? 32.6 Section 32.6 Wildlife and Fisheries UNITED STATES FISH... sport fishing regulations? (a) Refuge-specific fishing regulations are issued only at the time of or after the opening of a wildlife refuge area to sport fishing. (b) Refuge-specific fishing...

  2. 50 CFR 32.6 - What are the procedures for publication of refuge-specific sport fishing regulations?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... refuge-specific sport fishing regulations? 32.6 Section 32.6 Wildlife and Fisheries UNITED STATES FISH... sport fishing regulations? (a) Refuge-specific fishing regulations are issued only at the time of or after the opening of a wildlife refuge area to sport fishing. (b) Refuge-specific fishing...

  3. Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat.

    PubMed Central

    Tseng, C C; Kieffer, T J; Jarboe, L A; Usdin, T B; Wolfe, M M

    1996-01-01

    Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid peptide produced by K cells of the mammalian proximal small intestine and is a potent stimulant of insulin release in the presence of hyperglycemia. However, its relative physiological importance as a postprandial insulinotropic agent is unknown. Using LGIPR2 cells stably transfected with rat GIP receptor cDNA, GIP (1-42) stimulation of cyclic adenosine monophosphate (cAMP) production was inhibited in a concentration-dependent manner by GIP (7-30)-NH2. Competition binding assays using stably transfected L293 cells demonstrated an IC50 for GIP receptor binding of 7 nmol/liter for GIP (1-42) and 200 nmol/liter for GIP (7-30)-NH2, whereas glucagonlike peptide-1 (GLP-1) binding to its receptor on ++betaTC3 cells was minimally displaced by GIP (7-30)-NH2. In fasted anesthetized rats, GIP (1-42) stimulated insulin release in a concentration-dependent manner, an effect abolished by the concomitant intraperitoneal administration of GIP (7-30)-NH2 (100 nmol/ kg). In contrast, glucose-, GLP-1-, and arginine-stimulated insulin release were not affected by GIP (7-30)-NH2. In separate experiments, GIP (7-30)-NH2 (100 nmol/kg) reduced postprandial insulin release in conscious rats by 72%. It is concluded that GIP (7-30)-NH2 is a GIP-specific receptor antagonist and that GIP plays a dominant role in mediating postprandial insulin release. PMID:8958204

  4. Manual gas tungsten arc (dc) and semiautomatic gas metal arc welding of 6XXX aluminum. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-1009 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for manual gas tungsten arc (DC) and semiautomatic gas metal arc (DC) welding of aluminum alloys 6061 and 6063 (P-23), in thickness range 0.187 to 2 in.; filler metal is ER4043 (F-23); shielding gases are helium (GTAW) and argon (GMAW).

  5. Synbiotics suppress the release of lactate dehydrogenase, promote non-specific immunity and integrity of jejunum mucosa in piglets.

    PubMed

    Andrejčáková, Zuzana; Sopková, Drahomíra; Vlčková, Radoslava; Kulichová, Lucia; Gancarčíková, Soňa; Almášiová, Viera; Holovská, Katarína; Petrilla, Vladimír; Krešáková, Lenka

    2016-09-01

    The aim of our experiment was to study how synbiotics are able to deal with the problems of post-weaning piglets. Lactobacillus plantarum - Biocenol(TM) LP96 (CCM 7512), Lactobacillus fermentum - Biocenol(TM) LF99 (CCM 7514) and flaxseed (rich in n-3 polyunsaturated fatty acids) were administered to 36 conventional piglets from a problematic breed with confirmed presence of enterotoxigenic Escherichia coli and Coronavirus. The experimental piglets were supplied with probiotic cheeses and crushed flax-seed in the period starting 10 days before weaning and lasting up to 14 days post-weaning. Piglets in the control group were supplied only control cheese. The impact of such additives on the release of lactate dehydrogenase (LDH; spectroscopic and electrophoretic assay), alteration of immunity (index of metabolic activity), jejunum histology (light microscopy), and health of conventional piglets from a problematic breed (monitoring of hematology, consistency and moisture of feces and body temperature) were examined. We found significant decrease in LDH leakage in the blood serum and tissue extracts, indicating better cell membrane integrity in the individual organs of animals. Probiotics and flaxseed applied together seem to be a good source of nutrients to improve the immune status and the integrity of jejunum mucosa during infection. © 2015 Japanese Society of Animal Science. © 2015 Japanese Society of Animal Science.

  6. Meeting report: applied biopharmaceutics and quality by design for dissolution/release specification setting: product quality for patient benefit.

    PubMed

    Selen, Arzu; Cruañes, Maria T; Müllertz, Anette; Dickinson, Paul A; Cook, Jack A; Polli, James E; Kesisoglou, Filippos; Crison, John; Johnson, Kevin C; Muirhead, Gordon T; Schofield, Timothy; Tsong, Yi

    2010-09-01

    A biopharmaceutics and Quality by Design (QbD) conference was held on June 10-12, 2009 in Rockville, Maryland, USA to provide a forum and identify approaches for enhancing product quality for patient benefit. Presentations concerned the current biopharmaceutical toolbox (i.e., in vitro, in silico, pre-clinical, in vivo, and statistical approaches), as well as case studies, and reflections on new paradigms. Plenary and breakout session discussions evaluated the current state and envisioned a future state that more effectively integrates QbD and biopharmaceutics. Breakout groups discussed the following four topics: Integrating Biopharmaceutical Assessment into the QbD Paradigm, Predictive Statistical Tools, Predictive Mechanistic Tools, and Predictive Analytical Tools. Nine priority areas, further described in this report, were identified for advancing integration of biopharmaceutics and support a more fundamentally based, integrated approach to setting product dissolution/release acceptance criteria. Collaboration among a broad range of disciplines and fostering a knowledge sharing environment that places the patient's needs as the focus of drug development, consistent with science- and risk-based spirit of QbD, were identified as key components of the path forward.

  7. Region-Specific Onset of Handling-Induced Changes in Corticotropin-Releasing Factor and Glucocorticoid Receptor Expression

    PubMed Central

    Fenoglio, Kristina A.; Brunson, Kristen L.; Avishai-Eliner, Sarit; Chen, Yuncai; Baram, Tallie Z.

    2011-01-01

    Early-life experience including maternal care profoundly influences hormonal stress responses during adulthood. Daily handling on postnatal day (P) 2–9, eliciting augmented maternal care upon returning pups to their cage, permanently modifies the expression of the stress neuromodulators corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR). We have previously demonstrated reduced hypothalamic CRF expression already at the end of the handling period, followed by enhanced hippocampal GR mRNA levels (by P45). However, the initial site(s) and time of onset of these enduring changes have remained unclear. Therefore, we used semiquantitative in situ hybridization to delineate the spatiotemporal evolution of CRF and GR expression throughout stress-regulatory brain regions in handled (compared with undisturbed) pups. Enhanced CRF mRNA expression was apparent in the amygdaloid central nucleus (ACe) of handled pups already by P6. By P9, the augmented CRF mRNA levels persisted in ACe, accompanied by increased peptide expression in the bed nucleus of the stria terminalis and reduced expression in the paraventricular nucleus. The earliest change in GR consisted of reduced expression in the ACe of handled pups on P9, a time point when hippocampal GR expression was not yet affected. Thus, altered gene expression in ACe, bed nucleus of the stria terminalis as well as paraventricular nucleus may contribute to the molecular cascade by which handling (and increased maternal care) influences the stress response long term. PMID:15044366

  8. The specific monomer/dimer equilibrium of the corticotropin-releasing factor receptor type 1 is established in the endoplasmic reticulum.

    PubMed

    Teichmann, Anke; Gibert, Arthur; Lampe, André; Grzesik, Paul; Rutz, Claudia; Furkert, Jens; Schmoranzer, Jan; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

    2014-08-29

    G protein-coupled receptors (GPCRs) represent the most important drug targets. Although the smallest functional unit of a GPCR is a monomer, it became clear in the past decades that the vast majority of the receptors form dimers. Only very recently, however, data were presented that some receptors may in fact be expressed as a mixture of monomers and dimers and that the interaction of the receptor protomers is dynamic. To date, equilibrium measurements were restricted to the plasma membrane due to experimental limitations. We have addressed the question as to where this equilibrium is established for the corticotropin-releasing factor receptor type 1. By developing a novel approach to analyze single molecule fluorescence cross-correlation spectroscopy data for intracellular membrane compartments, we show that the corticotropin-releasing factor receptor type 1 has a specific monomer/dimer equilibrium that is already established in the endoplasmic reticulum (ER). It remains constant at the plasma membrane even following receptor activation. Moreover, we demonstrate for seven additional GPCRs that they are expressed in specific but substantially different monomer/dimer ratios. Although it is well known that proteins may dimerize in the ER in principle, our data show that the ER is also able to establish the specific monomer/dimer ratios of GPCRs, which sheds new light on the functions of this compartment.

  9. Manual gas tungsten arc and semiautomatic gas metal arc welding of chromium-nickel steel. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-306-ASME-6 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for manual gas tungsten arc and semiautomatic gas metal arc welding of 300 Series Cr-Ni steels (P-8-1), in thickness range 0.375 to 2 inch; filler metal is ER3XX (F-6, A-8); shielding gases are argon (GTAW) and 98-2 argon-oxygen.

  10. Machine gas tungsten arc and machine gas metal arc welding of chromium-nickel steel. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-309-ASME-0 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for machine gas tungsten arc and machine gas metal arc welding of 300 Series Cr-Ni steels (P-8-1), in thickness range 0.375 to 2 inch; filler metal is ER3XX (F-6,A-8); shielding gases are argon (GTAW) and 98-2 argon-oxygen (GMAW).

  11. Gas tungsten arc and shielded metal arc welding of carbon steel to chromium-nickel steel. Welding procedure specification

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

    1985-08-01

    Procedure WPS-2103-ASME-1 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc and shielded metal arc welding of carbon steels (P-1-1) to 300 series Cr-Ni steels (P-8-1), in thickness range 0.25 to 2 in.; filler metals are ERNiCr-3 (F-43) (GTAW) and ENiCrFe-3 (F-43) (SMAW); shielding gas is argon (GTAW).

  12. Specific LED-based red light photo-stimulation procedures improve overall sperm function and reproductive performance of boar ejaculates

    PubMed Central

    Yeste, Marc; Codony, Francesc; Estrada, Efrén; Lleonart, Miquel; Balasch, Sam; Peña, Alejandro; Bonet, Sergi; Rodríguez-Gil, Joan E.

    2016-01-01

    The present study evaluated the effects of exposing liquid-stored boar semen to different red light LED regimens on sperm quality and reproductive performance. Of all of the tested photo-stimulation procedures, the best pattern consisted of 10 min light, 10 min rest and 10 min of further light (10-10-10 pattern). This pattern induced an intense and transient increase in the majority of motility parameters, without modifying sperm viability and acrosome integrity. While incubating non-photo-stimulated sperm at 37 °C for 90 min decreased all sperm quality parameters, this reduction was prevented when the previously-described light procedure was applied. This effect was concomitant with an increase in the percentage of sperm with high mitochondrial membrane potential. When sperm were subjected to ‘in vitro’ capacitation, photo-stimulation also increased the percentage of sperm with capacitation-like changes in membrane structure. On the other hand, treating commercial semen doses intended for artificial insemination with the 10-10-10 photo-stimulation pattern significantly increased farrowing rates and the number of both total and live-born piglets for parturition. Therefore, our results indicate that a precise photo-stimulation procedure is able to increase the fertilising ability of boar sperm via a mechanism that could be related to mitochondrial function. PMID:26931070

  13. Specific LED-based red light photo-stimulation procedures improve overall sperm function and reproductive performance of boar ejaculates.

    PubMed

    Yeste, Marc; Codony, Francesc; Estrada, Efrén; Lleonart, Miquel; Balasch, Sam; Peña, Alejandro; Bonet, Sergi; Rodríguez-Gil, Joan E

    2016-03-02

    The present study evaluated the effects of exposing liquid-stored boar semen to different red light LED regimens on sperm quality and reproductive performance. Of all of the tested photo-stimulation procedures, the best pattern consisted of 10 min light, 10 min rest and 10 min of further light (10-10-10 pattern). This pattern induced an intense and transient increase in the majority of motility parameters, without modifying sperm viability and acrosome integrity. While incubating non-photo-stimulated sperm at 37 °C for 90 min decreased all sperm quality parameters, this reduction was prevented when the previously-described light procedure was applied. This effect was concomitant with an increase in the percentage of sperm with high mitochondrial membrane potential. When sperm were subjected to 'in vitro' capacitation, photo-stimulation also increased the percentage of sperm with capacitation-like changes in membrane structure. On the other hand, treating commercial semen doses intended for artificial insemination with the 10-10-10 photo-stimulation pattern significantly increased farrowing rates and the number of both total and live-born piglets for parturition. Therefore, our results indicate that a precise photo-stimulation procedure is able to increase the fertilising ability of boar sperm via a mechanism that could be related to mitochondrial function.

  14. A Collaborative Approach to Building a Terminology for Medical Procedures using a Web-based Application : From Specifications to daily use

    PubMed Central

    Burgun, Anita; Bodenreider, Olivier; Denier, Patrick; Delamarre, Denis; Botti, Geneviève; Oberlin, Philippe; Lévêque, Jean-Michel; Brémond, Marc; Fieschi, Mario; Beux, Pierre Le

    2015-01-01

    The MAOUSSC (Model for Assistance in the Orientation of a User within Coding Systems) Web server supports a collaborative work on the description of medical procedures. The specifications for the MAOUSSC application are conceptual modeling, definition of semantically fully described procedures, re-use of an existing vocabulary, the UMLS, and sharability. This paper reports on some difficulties in applying those principles in a networked building and updating of the terminology. The users are physicians who have to represent procedure terms in the MAOUSSC formalism. They must apply the constraints of the underlying model, and re-use the representation of the UMLS knowledge base. In our experience, we found that the implementation of syntactic and semantic constraints was not sufficient. Guidelines for pragmatical aspects in representation are required to make a collaborative approach in terminology building more operational. PMID:10384524

  15. Trajectories of tuberculosis-specific interferon-gamma release assay responses among medical and nursing students in rural India.

    PubMed

    Zwerling, Alice; Joshi, Rajnish; Kalantri, S P; Dakshinamoorthy, Gajalakshmi; Reddy, Maryada Venkatarama; Benedetti, Andrea; Schwartzman, Kevin; Menzies, Dick; Pai, Madhukar

    2013-06-01

    Interferon gamma release assays (IGRAs) have been shown to be highly dynamic tests when used in serial testing for TB infection. However, there is little information demonstrating a clear association between TB exposure and IGRA responses over time, particularly in high TB incidence settings. To assess whether QuantiFERON-TB Gold In-Tube (QFT) responses are associated with occupational TB exposures in a cohort of young health care trainees in India. All medical and nursing students at Mahatma Gandhi Institute of Medical Sciences were approached. Participants were followed up for 18 months; QFT was performed 4 times, once every 6 months. Various modeling approaches were used to define IFN-gamma trajectories and correlations with TB exposure. Among 270 medical and nursing trainees, high rates of conversions (6.3-20.9%) and reversions (20.0-26.2%) were found depending on the definitions used. Stable converters were more likely to have had TB exposure in hospital pre-study. Recent occupational exposures were not consistently associated with QFT responses over time. IFN-gamma responses and rates of change could not be explained by occupational exposure investigated. High conversion and subsequent reversion rates suggest many health care workers (HCWs) would revert in the absence of treatment, either by clearing the infection naturally or due to fluctuations in the underlying immunological response and/or poor assay reproducibility. QFT may not be an ideal diagnostic test for repeated screening of HCWs in a high TB incidence setting. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  16. Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications.

    PubMed

    Selivanova, Svetlana V; Lavallée, Éric; Senta, Helena; Caouette, Lyne; Sader, Jayden A; van Lier, Erik J; Zyuzin, Alexander; van Lier, Johan E; Guérin, Brigitte; Turcotte, Éric; Lecomte, Roger

    2015-10-01

    and contrast with cyclotron-produced 99mTc were equivalent to those obtained with 99mTc eluted from a conventional generator. Clinical-grade sodium pertechnetate 99mTc was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced 99mTc in routine clinical practice. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  17. Identification of a novel pituitary-specific chicken gonadotropin-releasing hormone receptor and its splice variants.

    PubMed

    Shimizu, Mamiko; Bédécarrats, Grégoy Y

    2006-11-01

    In all vertebrates, GnRH regulates gonadotropin secretion through binding to a specific receptor on the surface of pituitary gonadotropes. At least two forms of GnRH exist within a single species, and several corresponding GnRH receptors (GNRHRs) have been isolated with one form being pituitary specific. In chickens, only one type of widely expressed GNRHR has previously been identified. The objectives of this study were to isolate a chicken pituitary-specific GNRHR and to determine its expression pattern during a reproductive cycle. Using a combined strategy of PCR and rapid amplification of cDNA ends (RACE), a new GNRHR (chicken GNRHR2) and two splice variants were isolated in domestic fowl (Gallus gallus domesticus). Full-length GNRHR2 and one of its splice variant mRNAs were expressed exclusively in the pituitary, whereas mRNA of the other splice variant was expressed in most brain tissues examined. The deduced amino acid sequence of full-length chicken GNRHR2 reveals a seven transmembrane domain protein with 57%-65% homology to nonmammalian GNRHRs. Semiquantitative real-time PCR revealed that mRNA levels of full-length chicken GNRHR2 in the pituitary correlate with the reproductive status of birds, with maximum levels observed during the peak of lay and 4 wk postphotostimulation in females and males, respectively. Furthermore, GnRH stimulation of GH3 cells that were transiently transfected with cDNA that encodes chicken GNRHR2 resulted in a significant increase in inositol phosphate accumulation. In conclusion, we isolated a novel GNRHR and its splice variants in chickens, and spatial and temporal gene expression patterns suggest that this receptor plays an important role in the regulation of reproduction.

  18. 50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... and publication of the opening of a wildlife refuge area to migratory game bird, upland game or big game hunting. (b) Refuge-specific hunting regulations may contain the following items: (1) Wildlife...

  19. 50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... and publication of the opening of a wildlife refuge area to migratory game bird, upland game or big game hunting. (b) Refuge-specific hunting regulations may contain the following items: (1) Wildlife...

  20. Virgin Caenorhabditis remanei females are attracted to a coital pheromone released by con-specific copulating males

    PubMed Central

    Markert, Mathew; García, Luis René

    2013-01-01

    The gonochoristic soil nematode Caenorhabditis remanei strictly requires copulation for species propagation. Males of this species are sexually promiscuous with females of other species; therefore, we asked in this study whether virgin C. remanei females display evidence of mate choice. We digitally recorded and measured the locomotor behaviors of one or more virgin females in the presence of a single male on a 5 mm diameter mating lawn. We observed that initially only the male modifies his locomotor trajectory to another animal on the mating lawn; the virgin females showed no locomotor bias toward the mate-searching male. However, once a male started to copulate, females in the vicinity altered their movement trajectories toward the copulating couple. Newly inseminated females are refractive to the coital signal, but partially regain their attraction to copulating males after 24 h. We found only copulating males with an intact gonad can attract females, and that the coital signal can be broadcasted at least 1.5 mm through the air. Unlike males, which are also attracted to hetero-specific females, virgin C. remanei females will only crawl toward a copulating con-specific male. We suggest that Caenorhabditis females use the coital signal as a pheromone to identify a vigorous male of their own species. PMID:24058874

  1. All-Cause and Cause-Specific Mortality Among Men Released From State Prison, 1980–2005

    PubMed Central

    Rosen, David L.; Wohl, David A.

    2008-01-01

    Objectives. We compared mortality of ex-prisoners and other state residents to identify unmet health care needs among former prisoners. Methods. We linked North Carolina prison records with state death records for 1980 to 2005 to estimate the number of overall and cause-specific deaths among male ex-prisoners aged 20 to 69 years and used standardized mortality ratios (SMRs) to compare these observed deaths with the number of expected deaths had they experienced the same age-, race-, and cause-specific death rates as other state residents. Results. All-cause mortality among White (SMR = 2.08; 95% confidence interval [CI] = 2.04, 2.13) and Black (SMR = 1.03; 95% CI = 1.01, 1.05) ex-prisoners was greater than for other male NC residents. Ex-prisoners' deaths from homicide, accidents, substance use, HIV, liver disease, and liver cancer were greater than the expected number of deaths estimated using death rates among other NC residents. Deaths from cardiovascular disease, lung cancer, respiratory diseases, and diabetes were at least 30% greater than expected for White ex-prisoners, but less than expected for Black ex-prisoners. Conclusions. Ex-prisoners experienced more deaths than would have been expected among other NC residents. Excess deaths from injuries and medical conditions common to prison populations highlight ex-prisoners' medical vulnerability and the need to improve correctional and community preventive health services. PMID:18923131

  2. Association of the physical and chemical properties and the cytotoxicity of metal oxide nanoparticles: metal ion release, adsorption ability and specific surface area.

    PubMed

    Horie, Masanori; Fujita, Katsuhide; Kato, Haruhisa; Endoh, Shigehisa; Nishio, Keiko; Komaba, Lilian Kaede; Nakamura, Ayako; Miyauchi, Arisa; Kinugasa, Shinichi; Hagihara, Yoshihisa; Niki, Etsuo; Yoshida, Yasukazu; Iwahashi, Hitoshi

    2012-04-01

    Association of cellular influences and physical and chemical properties were examined for 24 kinds of industrial metal oxide nanoparticles: ZnO, CuO, NiO, Sb(2)O(3), CoO, MoO(3), Y(2)O(3), MgO, Gd(2)O(3), SnO(2), WO(3), ZrO(2), Fe(2)O(3), TiO(2), CeO(2), Al(2)O(3), Bi(2)O(3), La(2)O(3), ITO, and cobalt blue pigments. We prepared a stable medium dispersion for each nanoparticle and examined the influence on cell viability and oxidative stress together with physical and chemical characterizations. ZnO, CuO, NiO, MgO, and WO(3) showed a large amount of metal ion release in the culture medium. The cellular influences of these soluble nanoparticles were larger than insoluble nanoparticles. TiO(2), SnO(2), and CeO(2) nanoparticles showed strong protein adsorption ability; however, cellular influences of these nanoparticles were small. The primary particle size and the specific surface area seemed unrelated to cellular influences. Cellular influences of metal oxide nanoparticles depended on the kind and concentrations of released metals in the solution. For insoluble nanoparticles, the adsorption property was involved in cellular influences. The primary particle size and specific surface area of metal oxide nanoparticles did not affect directly cellular influences. In conclusion the most important cytotoxic factor of metal oxide nanoparticles was metal ion release. This journal is © The Royal Society of Chemistry 2012

  3. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation.

    PubMed

    Bieszczad, Kasia M; Bechay, Kiro; Rusche, James R; Jacques, Vincent; Kudugunti, Shashi; Miao, Wenyan; Weinberger, Norman M; McGaugh, James L; Wood, Marcelo A

    2015-09-23

    Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories. Significance statement: Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by

  4. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation

    PubMed Central

    Bechay, Kiro; Rusche, James R.; Jacques, Vincent; Kudugunti, Shashi; Miao, Wenyan; Weinberger, Norman M.; McGaugh, James L.

    2015-01-01

    Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories. SIGNIFICANCE STATEMENT Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by

  5. Double-blotting: a solution to the problem of non-specific binding of secondary antibodies in immunoblotting procedures.

    PubMed

    Lasne, F

    2001-07-01

    "Double-blotting" (DB) was developed to overcome the problem of non-specific binding of secondary antibodies in immunoblotting (IB). After it had been probed by the primary antibody, the membrane with the blotted proteins was assembled with a second blank membrane and submitted to a second blotting under acidic conditions. The primary antibody molecules were thus desorbed from their corresponding antigen and transferred onto the second membrane, whereas the antigen and the interfering proteins remained bound to the first one. The second membrane could then be probed by the secondary antibodies without the risk of non-specific binding. This method was developed for the study of erythropoietin (EPO) in concentrated urine since a strong non-specific binding of biotinylated secondary antibodies to some urinary proteins had been observed using classical IB protocols.

  6. File Specification for the 7-km GEOS-5 Nature Run, Ganymed Release Non-Hydrostatic 7-km Global Mesoscale Simulation

    NASA Technical Reports Server (NTRS)

    da Silva, Arlindo M.; Putman, William; Nattala, J.

    2014-01-01

    details about variables listed in this file specification can be found in a separate document, the GEOS-5 File Specification Variable Definition Glossary. Documentation about the current access methods for products described in this document can be found on the GEOS-5 Nature Run portal: http://gmao.gsfc.nasa.gov/projects/G5NR. Information on the scientific quality of this simulation will appear in a forthcoming NASA Technical Report Series on Global Modeling and Data Assimilation to be available from http://gmao.gsfc.nasa.gov/pubs/tm/.

  7. Lexical Training through Modeling and Elicitation Procedures with Late Talkers Who Have Specific Language Impairment and Developmental Delays

    ERIC Educational Resources Information Center

    Kouri, Theresa A.

    2005-01-01

    Late talkers with specific language impairment and developmental delay make up a large portion of our early childhood caseloads; therefore, an understanding of best clinical practices for these populations is essential. Early lexical learning was examined in 2 interactive treatment approaches with 29 late-talking preschoolers with language and…

  8. Review: A Position Paper on Selenium in Ecotoxicology: A Procedure for Deriving Site-Specific Water Quality Criteria

    Treesearch

    A. Dennis Lemly

    1997-01-01

    This paper describes a method for deriving site-specific water quality criteria for selenium using a two-step process: (1) gather information on selenium residues and biological effects at the site and in down-gradient systems and (2) examine criteria based on the degree of bioaccumulation, the relationship between mea-sured residues and threshold concentrations for...

  9. An S-phase specific release from a transcriptional block regulates the expression of mouse ribonucleotide reductase R2 subunit.

    PubMed Central

    Björklund, S; Skogman, E; Thelander, L

    1992-01-01

    Ribonucleotide reductase (RR) activity in mammalian cells is closely linked to DNA synthesis. The RR enzyme is composed of two non-identical subunits, proteins R1 and R2. Both proteins are required for holoenzyme activity, which is regulated by S-phase specific de novo synthesis and breakdown of the R2 subunit. In quiescent cells stimulated to proliferate and in elutriated cell populations enriched in the various cell cycle phases the R2 protein levels are correlated to R2 mRNA levels that are low in G0/G1-phase cells but increase dramatically at the G1/S border. Using an R2 promoter-luciferase reporter gene construct we demonstrate an unexpected early activation of the R2 promoter as cells pass from quiescence to proliferation. However, due to a transcriptional block, this promoter activation only results in very short R2 transcripts until cells enter the S-phase, when full-length R2 transcripts start to appear. The position for the transcriptional block was localized to a nucleotide sequence approximately 87 bp downstream from the first exon/intron boundary by S1 nuclease mapping of R2 transcripts from modified in vitro nuclear run-on experiments. These results identify blocking of transcription as a mechanism to control cell cycle regulated gene expression. Images PMID:1464320

  10. Phylogenetic Footprinting Reveals Evolutionarily Conserved Regions of the Gonadotropin-Releasing Hormone Gene that Enhance Cell-Specific Expression

    PubMed Central

    GIVENS, MARJORY L.; KUROTANI, REIKO; RAVE-HAREL, NAAMA; MILLER, NICHOL L. G.; MELLON, PAMELA L.

    2010-01-01

    Reproductive function is controlled by the hypothalamic neuropeptide, GnRH, which serves as the central regulator of the hypothalamic-pituitary-gonadal axis. GnRH expression is limited to a small population of neurons in the hypothalamus. Targeting this minute population of neurons (as few as 800 in the mouse) requires regulatory elements upstream of the GnRH gene that remain to be fully characterized. Previously, we have identified an evolutionarily conserved promoter region (−173 to −1) and an enhancer (−1863 to −1571) in the rat gene that targets a subset of the GnRH neurons in vivo. In the present study, we used phylogenetic sequence comparison between human and rodents and analysis of the transcription factor clusters within conserved regions in an attempt to identify additional upstream regulatory elements. This approach led to the characterization of a new upstream enhancer that regulates expression of GnRH in a cell-specific manner. Within this upstream enhancer are nine binding sites for Octamer-binding transcription factor 1 (OCT1), known to be an important transcriptional regulator of GnRH gene expression. In addition, we have identified nuclear factor I (NF1) binding to multiple elements in the GnRH-regulatory regions, each in close proximity to OCT1. We show that OCT1 and NF1 physically and functionally interact. Moreover, the OCT1 and NF1 binding sites in the regulatory regions appear to be essential for appropriate GnRH gene expression. These findings indicate a role for this upstream enhancer and novel OCT1/NF1 complexes in neuron-restricted expression of the GnRH gene. PMID:15319450

  11. Analog specificity of the thyrotropin-releasing hormone receptor in the central nervous system: possible clinical implications

    SciTech Connect

    Hawkins, E.F.; Engel, W.K.

    1985-02-11

    TRH has rapid-onset (30 sec), slow-offset (1-12 days) clinical benefit in patients with amyotrophic lateral sclerosis and other motor neuron disorders. This benefit is probably receptor-mediated and may have at least 2 components. To obtain a better understanding of the various responses to TRH of the spinal lower motor neurons (LMNs) in patients, and possibly to help guide selection of additional therapeutic agents, the authors utilized rat CNS (spinal-cord and brain membranes) to analyze the ability of certain molecules to inhibit specific binding of (/sup 3/H)methyl TRH ((/sup 3/H)MeTRH) to the TRH receptor. They found: a) lack of high-affinity binding of the TRH-analog DN-1417 by spinal-cord and brain TRH receptor, despite its known strong TRH-like action physiologically on LMNs; b) lack of high-affinity binding of the TRH-product cyclo(His-Pro) by spinal cord and brain TRH receptor despite its having some strong TRH-like physiologic actions on the CNS; and c) lack of any identifiable high-affinity receptor for cyclo(His-Pro) in spinal cord and brain. From these data the authors hypothesize that the acute transmitter-like action of DN-1417, TRH, and possibly other TRH-analogs and products on LMNs is via a non-TRH receptor, such as an amine or amino acid neurotransmitter receptor, e.g. a 5-hydroxytryptamine receptor. They further postulate that the CNS TRH-receptor may modulate a trophic-like influence of TRH on LMNs.

  12. Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma.

    PubMed

    Don, Elena; Farafonova, Olga; Pokhil, Suzanna; Barykina, Darya; Nikiforova, Marina; Shulga, Darya; Borshcheva, Alena; Tarasov, Sergey; Ermolaeva, Tatyana; Epstein, Oleg

    2016-01-20

    In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%-6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF's ability to modify the affinity of IFNg to specific/related Abs.

  13. Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma

    PubMed Central

    Don, Elena; Farafonova, Olga; Pokhil, Suzanna; Barykina, Darya; Nikiforova, Marina; Shulga, Darya; Borshcheva, Alena; Tarasov, Sergey; Ermolaeva, Tatyana; Epstein, Oleg

    2016-01-01

    In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs. PMID:26791304

  14. 46 CFR 160.062-1 - Applicable specifications, and referenced material.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., Hydraulic and Manual § 160.062-1 Applicable specifications, and referenced material. (a) Specifications and...: MIL-R-15041C—Releases, lifesaving equipment, hydraulic and manual. MIL-STD-105—Sample procedures...

  15. 46 CFR 160.062-1 - Applicable specifications, and referenced material.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., Hydraulic and Manual § 160.062-1 Applicable specifications, and referenced material. (a) Specifications and...: MIL-R-15041C—Releases, lifesaving equipment, hydraulic and manual. MIL-STD-105—Sample procedures...

  16. 46 CFR 160.062-1 - Applicable specifications, and referenced material.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., Hydraulic and Manual § 160.062-1 Applicable specifications, and referenced material. (a) Specifications and...: MIL-R-15041C—Releases, lifesaving equipment, hydraulic and manual. MIL-STD-105—Sample procedures...

  17. 46 CFR 160.062-1 - Applicable specifications, and referenced material.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., Hydraulic and Manual § 160.062-1 Applicable specifications, and referenced material. (a) Specifications and...: MIL-R-15041C—Releases, lifesaving equipment, hydraulic and manual. MIL-STD-105—Sample procedures...

  18. 46 CFR 160.062-1 - Applicable specifications, and referenced material.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., Hydraulic and Manual § 160.062-1 Applicable specifications, and referenced material. (a) Specifications and...: MIL-R-15041C—Releases, lifesaving equipment, hydraulic and manual. MIL-STD-105—Sample procedures...

  19. National Uranium Resource Evaluation. General procedure for calibration and reduction of aerial gamma-ray measurements: specification BFEC 1250-B

    SciTech Connect

    Purvance, D.; Novak, E.

    1983-12-01

    The information contained in this specification was acquired over the course of the US Department of Energy (DOE) National Uranium Resource Evaluation (NURE) program during the period 1974 through 1982. NURE was a program of the DOE Grand Junction Area Office to acquire and compile geologic and other information with which to assess the magnitude and distribution of uranium resources and to determine areas favorable for the occurrence of uranium in the United States. Bendix Field Engineering Corporation (BFEC) has been the operating contractor for the DOE Grand Junction facility. The requirements stipulated herein had been incorporated as contractual specifications for the various subcontractors engaged in the aerial gamma-ray surveys, which were a major aspect of the NURE program. Although this phase of NURE activities has been completed, there exists valuable knowledge gained from these years of experience in the calibration of gamma-ray spectrometer systems and in the reduction of calibration data. Specification BFEC 1250-B is being open-filed by the US Department of Energy at this time to make this knowledge available to those desiring to apply gamma-ray spectrometry to other geophysical problems.

  20. Experimental design for the formulation and optimization of novel cross-linked oilispheres developed for in vitro site-specific release of Mentha piperita oil.

    PubMed

    Sibanda, Wilbert; Pillay, Viness; Danckwerts, Michael P; Viljoen, Alvaro M; van Vuuren, Sandy; Khan, Riaz A

    2004-03-12

    A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginate-pectinate oilisphere complex as a potential system for the in vitro site-specific release of Mentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%-1.5% wt/vol), crosslinkers (0%-4% wt/vol), and crosslinking reaction times (0.5-6 hours) (independent variables). Particle size analysis indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from 6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the total fracture energy was the most suitable optimization objective (R2 = 0.88, Durbin-Watson Index = 1.21%, Coefficient of Variation (CV) = 33.21%). The Lagrangian technique produced no significant differences (P > .05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks, as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network epoch approximately 0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n > 0.99), whereby analysis of release data indicated that diffusion (Fickian constant k1 = 0.74 vs relaxation constant k2 = 0.02) was the predominant release mechanism.

  1. Epidermal growth factor (EGF) ligand release by substrate-specific a disintegrin and metalloproteases (ADAMs) involves different protein kinase C (PKC) isoenzymes depending on the stimulus.

    PubMed

    Dang, Michelle; Dubbin, Karen; D'Aiello, Antonio; Hartmann, Monika; Lodish, Harvey; Herrlich, Andreas

    2011-05-20

    The dysregulation of EGF family ligand cleavage has severe consequences for the developing as well as the adult organism. Therefore, their production is highly regulated. The limiting step is the ectodomain cleavage of membrane-bound precursors by one of several a disintegrin and metalloprotease (ADAM) metalloproteases, and understanding the regulation of cleavage is an important goal of current research. We have previously reported that in mouse lung epithelial cells, the pro-EGF ligands TGFα, neuregulin 1β (NRG), and heparin-binding EGF are differentially cleaved depending on the cleavage stimulus (Herrlich, A., Klinman, E., Fu, J., Sadegh, C., and Lodish, H. (2008) FASEB J.). In this study in mouse embryonic fibroblasts that lack different ADAMs, we show that induced cleavage of EGF ligands can involve the same substrate-specific metalloprotease but does require different stimulus-dependent signaling pathways. Cleavage was stimulated by phorbol ester (12-O-tetradecanoylphorbol-13-acetate (TPA), a mimic of diacylglycerol and PKC activator), hypertonic stress, lysophosphatidic acid (LPA)-induced G protein-coupled receptor activation, or by ionomycin-induced intracellular calcium release. Although ADAMs showed substrate preference (ADAM17, TGFα and heparin-binding EGF; and ADAM9, NRG), substrate cleavage differed substantially with the stimulus, and cleavage of the same substrate depended on the presence of different, sometimes multiple, PKC isoforms. For instance, classical PKC was required for TPA-induced but not hypertonic stress-induced cleavage of all EGF family ligands. Inhibition of PKCζ enhanced NRG release upon TPA stimulation, but it blocked NRG release in response to hypertonic stress. Our results suggest a model in which substantial regulation of ectodomain cleavage occurs not only on the metalloprotease level but also on the level of the substrate or of a third protein.

  2. Detection of pork adulteration in processed meat by species-specific PCR-QIAxcel procedure based on D-loop and cytb genes.

    PubMed

    Barakat, Hassan; El-Garhy, Hoda A S; Moustafa, Mahmoud M A

    2014-12-01

    Detection of pork meat adulteration in "halal" meat products is a crucial issue in the fields of modern food inspection according to implementation of very strict procedures for halal food labelling. Present study aims at detecting and quantifying pork adulteration in both raw and cooked manufactured sausages. This is by applying an optimized species-specific PCR procedure followed by QIAxcel capillary electrophoresis system. Manufacturing experiment was designed by incorporating pork with beef meat at 0.01 to 10 % substitution levels beside beef and pork sausages as negative and positive controls, respectively. Subsequently, sausages were divided into raw and cooked sausages then subjected to DNA extraction. Results indicated that PCR amplifications of mitochondrial D-loop and cytochrome b (cytb) genes by porcine-specific primers produced 185 and 117 bp pork-specific DNA fragments in sausages, respectively. No DNA fragments were detected when PCR was applied on beef sausage DNA confirming primers specificity. For internal control, a 141-bp DNA fragment of eukaryotic 18S ribosomal RNA (rRNA) gene was amplified from pork and beef DNA templates. Although PCR followed by either QIAxcel or agarose techniques were efficient for targeted DNA fragments differentiation even as low as 0.01 % (pork/meat: w/w). For proficiency, adequacy, and performance, PCR-QIA procedure is highly sensitive, a time-saver, electronically documented, mutagenic-reagent free, of little manual errors, accurate in measuring PCR fragments length, and quantitative data supplier. In conclusion, it can be suggested that optimized PCR-QAI is considered as a rapid and sensitive method for routine pork detection and quantification in raw or processed meat.

  3. 43 CFR 11.36 - May the authorized official use both type A and type B procedures for the same release?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... and/or from population losses; (7) Lost recreational harvests resulting from any closures specified by the authorized official and/or from population losses; (8) For the type A procedure for coastal and marine environments, lost wildlife viewing, resulting from population losses, by residents of the States...

  4. Enhanced Blood Suspensibility and Laser-Activated Tumor-specific Drug Release of Theranostic Mesoporous Silica Nanoparticles by Functionalizing with Erythrocyte Membranes

    PubMed Central

    Su, Jinghan; Sun, Huiping; Meng, Qingshuo; Zhang, Pengcheng; Yin, Qi; Li, Yaping

    2017-01-01

    Mesoporous silica nanoparticles (MSNs), with their large surface area and tunable pore sizes, have been widely applied for anticancer therapeutic cargos delivery with a high loading capacity. However, easy aggregation in saline buffers and limited blood circulation lifetime hinder their delivery efficiency and the anticancer efficacy. Here, new multifunctional MSNs-supported red-blood-cell (RBC)-mimetic theranostic nanoparticles with long blood circulation, deep-red light-activated tumor imaging and drug release were reported. High loading capacities were achieved by camouflaging MSNs with RBC membrane to co-load an anticancer drug doxorubicin (Dox) (39.1 wt%) and a near-infrared photosensitizer chlorin e6 (Ce6) (21.1 wt%). The RBC membrane-coating protected drugs from leakage, and greatly improved the colloidal stability of MSNs, with negligible particle size change over two weeks. Upon an external laser stimuli, the RBC membrane could be destroyed, resulting in 10 times enhancement of Dox release. In a 4T1 breast cancer mouse model, the RBC-mimetic MSNs could realize in vivo tumor imaging with elongated tumor accumulation lifetime for over 24 h, and laser-activated tumor-specific Dox accumulation. The RBC-mimetic MSNs could integrate the Ce6-based photodynamic therapy and Dox-based chemotherapy, completely suppress the primary tumor growth and inhibit metastasis of breast cancer, which could provide a new strategy for optimization of MSNs and efficient anticancer drug delivery. PMID:28255347

  5. Isoform-Specific Interactions Between Halothane and the Ryanodine Receptor Ca2+-Release Channel: Implications for Malignant Hyperthermia and the Protein Theory of Anaesthetic Action

    NASA Astrophysics Data System (ADS)

    Frömming, G. R.; Ohlendieck, K.

    General anaesthetics exhibit a relatively close relationship between their pharmacological potency and their lipid solubility and may thus act by non-specific perturbation of biomembranes. However, more recent data on anaesthetic action suggests that inhalational drugs such as halothane bind directly to hydrophobic protein domains, thereby modulating important receptor functions. In support of this protein theory of anaesthetic action our native gel analysis presented here shows that halothane induces oligomerization of the skeletal muscle ryanodine receptor (RyR) 1 Ca2+-release channel, but not its cardiac RyR-2 isoform. Thus, inhalational anaesthetics are not only able to influence protein-protein interactions directly but also appear to differentiate between protein isoforms and/or configurations. This suggests that distinct peptide binding sites exist for these pharmacological agents. In addition, similar mutations in the RyR-2 isoform, which would trigger an episode of malignant hyperthermia in skeletal muscle fibres via abnormal RyR-1 isoforms, would probably not induce an increase in cardiac Ca2+-release upon administration of halothane.

  6. Birch (Betula spp.) leaves adsorb and re-release volatiles specific to neighbouring plants--a mechanism for associational herbivore resistance?

    PubMed

    Himanen, Sari J; Blande, James D; Klemola, Tero; Pulkkinen, Juha; Heijari, Juha; Holopainen, Jarmo K

    2010-05-01

    Plant-emitted semi-volatile compounds have low vaporization rates at 20-25 degrees C and may therefore persist on surfaces such as plant foliage. The passive adsorption of arthropod-repellent semi-volatiles to neighbouring foliage could convey associational resistance, whereby a plant's neighbours reduce damage caused by herbivores. We found that birch (Betula spp.) leaves adsorb and re-release the specific arthropod-repelling C(15) semi-volatiles ledene, ledol and palustrol produced by Rhododendron tomentosum when grown in mixed association in a field setup. In a natural habitat, a higher concentration of ledene was released from birches neighbouring R. tomentosum than from birches situated > 5 m from R. tomentosum. Emission of alpha-humulene, a sesquiterpene synthesized by both Betula pendula and R. tomentosum, was also increased in R. tomentosum-neighbouring B. pendula. In assessments for associational resistance, we found that the polyphagous green leaf weevils (Polydrusus flavipes) and autumnal moth (Epirrita autumnata) larvae both preferred B. pendula to R. tomentosum. P. flavipes also preferred birch leaves not exposed to R. tomentosum to leaves from mixed associations. In the field, a reduction in Euceraphis betulae aphid density occurred in mixed associations. Our results suggest that plant/tree species may be protected by semi-volatile compounds emitted by a more herbivore-resistant heterospecific neighbour.

  7. An efficient procedure for marker-free mutagenesis of S. coelicolor by site-specific recombination for secondary metabolite overproduction.

    PubMed

    Zhang, Bo; Zhang, Lin; Dai, Ruixue; Yu, Meiying; Zhao, Guoping; Ding, Xiaoming

    2013-01-01

    Streptomyces bacteria are known for producing important natural compounds by secondary metabolism, especially antibiotics with novel biological activities. Functional studies of antibiotic-biosynthesizing gene clusters are generally through homologous genomic recombination by gene-targeting vectors. Here, we present a rapid and efficient method for construction of gene-targeting vectors. This approach is based on Streptomyces phage φBT1 integrase-mediated multisite in vitro site-specific recombination. Four 'entry clones' were assembled into a circular plasmid to generate the destination gene-targeting vector by a one-step reaction. The four 'entry clones' contained two clones of the upstream and downstream flanks of the target gene, a selectable marker and an E. coli-Streptomyces shuttle vector. After targeted modification of the genome, the selectable markers were removed by φC31 integrase-mediated in vivo site-specific recombination between pre-placed attB and attP sites. Using this method, part of the calcium-dependent antibiotic (CDA) and actinorhodin (Act) biosynthetic gene clusters were deleted, and the rrdA encoding RrdA, a negative regulator of Red production, was also deleted. The final prodiginine production of the engineered strain was over five times that of the wild-type strain. This straightforward φBT1 and φC31 integrase-based strategy provides an alternative approach for rapid gene-targeting vector construction and marker removal in streptomycetes.

  8. The pH-dependent Client Release from the Collagen-specific Chaperone HSP47 Is Triggered by a Tandem Histidine Pair.

    PubMed

    Oecal, Sinan; Socher, Eileen; Uthoff, Matthias; Ernst, Corvin; Zaucke, Frank; Sticht, Heinrich; Baumann, Ulrich; Gebauer, Jan M

    2016-06-10

    Heat shock protein 47 (HSP47) is an endoplasmic reticulum (ER)-resident collagen-specific chaperone and essential for proper formation of the characteristic collagen triple helix. It preferentially binds to the folded conformation of its clients and accompanies them from the ER to the Golgi compartment, where it releases them and is recycled back to the ER. Unlike other chaperones, the binding and release cycles are not governed by nucleotide exchange and hydrolysis, but presumably the dissociation of the HSP47-procollagen complex is triggered by the lower pH in the Golgi (pH 6.3) compared with the ER (pH 7.4). Histidine residues have been suggested as triggers due to their approximate textbook pKa value of 6.1 for their side chains. We present here an extensive theoretical and experimental study of the 14 histidine residues present in canine HSP47, where we have mutated all histidine residues in the collagen binding interface and additionally all of those that were predicted to undergo a significant change in protonation state between pH 7 and 6. These mutants were characterized by biolayer interferometry for their pH-dependent binding to a collagen model. One mutant (H238N) loses binding, which can be explained by a rearrangement of the Arg(222) and Asp(385) residues, which are crucial for specific collagen recognition. Most of the other mutants were remarkably silent, but a double mutant with His(273) and His(274) exchanged for asparagines exhibits a much less pronounced pH dependence of collagen binding. This effect is mainly caused by a lower koff at the low pH values.

  9. The pH-dependent Client Release from the Collagen-specific Chaperone HSP47 Is Triggered by a Tandem Histidine Pair*

    PubMed Central

    Oecal, Sinan; Socher, Eileen; Uthoff, Matthias; Ernst, Corvin; Zaucke, Frank; Sticht, Heinrich; Baumann, Ulrich; Gebauer, Jan M.

    2016-01-01

    Heat shock protein 47 (HSP47) is an endoplasmic reticulum (ER)-resident collagen-specific chaperone and essential for proper formation of the characteristic collagen triple helix. It preferentially binds to the folded conformation of its clients and accompanies them from the ER to the Golgi compartment, where it releases them and is recycled back to the ER. Unlike other chaperones, the binding and release cycles are not governed by nucleotide exchange and hydrolysis, but presumably the dissociation of the HSP47-procollagen complex is triggered by the lower pH in the Golgi (pH 6.3) compared with the ER (pH 7.4). Histidine residues have been suggested as triggers due to their approximate textbook pKa value of 6.1 for their side chains. We present here an extensive theoretical and experimental study of the 14 histidine residues present in canine HSP47, where we have mutated all histidine residues in the collagen binding interface and additionally all of those that were predicted to undergo a significant change in protonation state between pH 7 and 6. These mutants were characterized by biolayer interferometry for their pH-dependent binding to a collagen model. One mutant (H238N) loses binding, which can be explained by a rearrangement of the Arg222 and Asp385 residues, which are crucial for specific collagen recognition. Most of the other mutants were remarkably silent, but a double mutant with His273 and His274 exchanged for asparagines exhibits a much less pronounced pH dependence of collagen binding. This effect is mainly caused by a lower koff at the low pH values. PMID:27129216

  10. Evaluation of VZV-specific cell-mediated immunity in adults infected with HIV-1 by using a simple IFN-γ release assay.

    PubMed

    Watanabe, Dai; Otani, Naruhito; Suzuki, Sachiko; Dohi, Hiromi; Hirota, Kazuyuki; Yonemoto, Hitoshi; Koizumi, Yusuke; Otera, Hiroshi; Yajima, Keishiro; Nishida, Yasuharu; Uehira, Tomoko; Shima, Masayuki; Shirasaka, Takuma; Okuno, Toshiomi

    2013-08-01

    The development of herpes zoster is associated with reduced varicella zoster virus (VZV)-specific cell-mediated immune (CMI) reactions. In this study, VZV-specific CMI reactions in 42 anti-VZV-IgG antibody-positive adults infected with HIV-1 were evaluated by measuring the IFN-γ production levels in whole blood in response to stimulation with ultraviolet light-inactivated live attenuated VZV vaccine. The median VZV-specific IFN-γ production level in all patients was 63 pg/ml. Antiretroviral therapy (ART)-naïve patients with an AIDS-defining illness (HIV classification category C) had significantly lower IFN-γ production than ART-naïve patients in categories A and B and patients receiving ART (P=0.0194 and P=0.0046, respectively). IFN-γ production increased significantly in patients within 1 month of the onset of recurrent VZV disease and at more than 1 year from onset, compared with patients who had never had recurrent VZV disease (P=0.0396 and P=0.0484, respectively). In multivariate analyses, category C and history of recurrent VZV disease were significant factors affecting IFN-γ production. Levels of IFN-γ were measured before and after ART in seven ART-naïve patients with no history of recurrent VZV disease, and no significant changes were observed. The results indicate that VZV-specific CMI reactions were reduced in patients with an AIDS-defining illness and enhanced in patients with a history of recurrent VZV disease, but not enhanced by ART alone. Vaccination may be necessary to inhibit the development of herpes zoster in patients receiving ART; this IFN-γ releasing assay is one useful method for evaluating VZV-specific CMI reactions in clinical settings. Copyright © 2013 Wiley Periodicals, Inc.

  11. General screening procedure for RNA modificationless mutants: isolation of Escherichia coli strains with specific defects in RNA methylation.

    PubMed Central

    Björk, G R; Kjellin-Stråby, K

    1978-01-01

    A general method for the isolation of mutants of Escherichia coli that are defective in RNA modification is described. The method is based on the fact that RNA with specific undermodifications accumulates under nonpermissive growth conditions and that such a defect can be detected by remodification either in vivo at permissive conditions or in vitro. The method provides a means by which to study mutations affecting essential modification reactions. The usefulness of the method was demonstrated by the isolation of two rRNA and two tRNA methylation defective mutants. Both rRNA mutants accept methyl groups into their 23S rRNA in vitro. Analyses of in vitro methylated 23S rRNA from one of the mutants revealed the presence of several methylated nucleosides, of which 6-methyladenosine was the most abundant (40% of recovered radioactivity). In 23S rRNA from the other mutant, the only product formed in vitro was 5-methylcytidine. The tRNA mutants are characterized in the accompanying paper. Images PMID:342494

  12. Stepwise effects of the BCR sequential chemical extraction procedure on dissolution and metal release from common ferromagnesian clay minerals: a combined solution chemistry and X-ray powder diffraction study.

    PubMed

    Ryan, P C; Hillier, S; Wall, A J

    2008-12-15

    Sequential extraction procedures (SEPs) are commonly used to determine speciation of trace metals in soils and sediments. However, the non-selectivity of reagents for targeted phases has remained a lingering concern. Furthermore, potentially reactive phases such as phyllosilicate clay minerals often contain trace metals in structural sites, and their reactivity has not been quantified. Accordingly, the objective of this study is to analyze the behavior of trace metal-bearing clay minerals exposed to the revised BCR 3-step plus aqua regia SEP. Mineral quantification based on stoichiometric analysis and quantitative powder X-ray diffraction (XRD) documents progressive dissolution of chlorite (CCa-2 ripidolite) and two varieties of smectite (SapCa-2 saponite and SWa-1 nontronite) during steps 1-3 of the BCR procedure. In total, 8 (+/-1) % of ripidolite, 19 (+/-1) % of saponite, and 19 (+/-3) % of nontronite (% mineral mass) dissolved during extractions assumed by many researchers to release trace metals from exchange sites, carbonates, hydroxides, sulfides and organic matter. For all three reference clays, release of Ni into solution is correlated with clay dissolution. Hydrolysis of relatively weak Mg-O bonds (362 kJ/mol) during all stages, reduction of Fe(III) during hydroxylamine hydrochloride extraction and oxidation of Fe(II) during hydrogen peroxide extraction are the main reasons for clay mineral dissolution. These findings underscore the need for precise mineral quantification when using SEPs to understand the origin/partitioning of trace metals with solid phases.

  13. RELEASE OF GENTAMICIN FROM CEMENT SPACERS IN TWO-STAGE PROCEDURES FOR HIP AND KNEE PROSTHETIC INFECTION: AN IN VIVO PHARMACOKINETIC STUDY WITH CLINICAL FOLLOW-UP.

    PubMed

    Balato, G; Ascione, T; Rosa, D; Pagliano, P; Solarino, G; Moretti, B; Mariconda, M

    2015-01-01

    Eighteen patients undergoing two-stage exchange arthroplasty for infected total hip or knee arthroplasty using gentamicin-loaded bone cement spacers (80g bone cement, 2 g gentamicin and 2 g clindamycin) were studied. The concentration of gentamicin eluted from the spacers was assessed on samples of blood, urine, and drainage fluid that were collected from each patient at set intervals during the 48 hours following the first-stage surgery. The hip and knee cement spacers showed similar curve of release over the first postoperative hours (early peak followed by slow release), but the mean gentamicin concentration in the drainage fluid was higher in patients with hip spacers compared to patients with knee spacers (30.61±19.47 mg/L vs 17.43±13,63 mg/L, p less than 0.05). In patients with hip spacers, the mean, maximum, and minimum concentration of gentamicin was higher with respect to the minimum inhibitory concentration (MIC) break point for Staphylococcus spp, Pseudomonas Aeruginosa and Enterobacteriaceae throughout the first postoperative 48 h. Conversely, in 25% of patients with a knee spacer a drug concentration below the MIC break point for Gram negative bacteria was found in the drainage fluid after 12 h. Gentamicin levels in the blood samples were negligible over the entire time interval and were steadily well below the renal toxicity reference. The highest urinary concentration of gentamicin was observed between 4 and 9 h postoperatively. Subsequently, it gradually declined until 48 h. Clinically, the rate of cure was 100% at a mean follow-up of 113 weeks (range 90-182). Gentamicin-loaded cement spacers offer the advantage of achieving early high concentrations of the antibiotic directly at the site of infection but especially in the knee a systemic antibiotic therapy must be given as a complement to the spacer implantation to eradicate periprosthetic joint infection (PJI).

  14. Release of palladium from biomechanical prostheses in body fluids can induce or support PD-specific IFNgamma T cell responses and the clinical setting of a palladium hypersensitivity.

    PubMed

    Cristaudo, A; Bordignon, V; Petrucci, F; Caimi, S; De Rocco, M; Picardo, M; Cordiali Fei, P; Ensoli, F

    2009-01-01

    The increased use of Palladium (Pd) for biomedical applications, which has more than doubled in the last ten years, appears to be associated with an increased frequency of adverse reactions to Pd. The aim of this study is to investigate the relationship between the implant of a biomechanical apparatus containing Pd and the setting of a hypersensitivity to Pd by determining the levels of the metal released in biological fluids, assessing the effects of Pd on peripheral blood mononuclear cell (PBMC) cytokine production and exploring the clinical setting of skin sensitization. Of a total of 3,093 subjects examined in 2006, sensitization to Pd alone or in association with nickel (Ni) was observed in 1.6% and 13.03% of the individuals, respectively. Of these, a group of six subjects positive to Pd and negative to Ni at patch testing were selected on the basis of the oral clinical symptoms in order to measure both the levels of Pd in biological fluids and the degradation of the dental prostheses. Specific Pd measurements were carried out on salivary fluid, urine and serum samples by High Resolution Inductively Coupled Plasma-Mass Spectrometry. In addition, the degradation of the dental prostheses was assessed by both a leaching test and an analysis of the micro morphology of orthodontic prostheses. The induction of IFN-gamma production by Pd was assessed in PBMC by the ELISpot assay. Skin sensitization to Pd was evaluated by patch testing and clinical examination. Ten healthy subjects were comparatively tested as controls. We found a specific induction of an IFN-gamma response by Pd in PBMC collected from all the subjects positive to Pd at patch testing. On the contrary, control subjects did not show any response to Pd as assessed by IFN-gamma ELISpot assay or by skin testing. Remarkably, the levels of Pd in all biological samples (saliva, sera, urine) were significantly higher in Pd-sensitized patients than in those collected from controls, reaching the highest

  15. Most-probable-number loop-mediated isothermal amplification-based procedure enhanced with K antigen-specific immunomagnetic separation for quantifying tdh(+) Vibrio parahaemolyticus in molluscan Shellfish.

    PubMed

    Tanaka, Natsuko; Iwade, Yoshito; Yamazaki, Wataru; Gondaira, Fumio; Vuddhakul, Varaporn; Nakaguchi, Yoshitsugu; Nishibuchi, Mitsuaki

    2014-07-01

    Although thermostable direct hemolysin-producing (tdh(+)) Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis, the enumeration of tdh(+) V. parahaemolyticus remains challenging due to its low densities in the environment. In this study, we developed a most-probable-number (MPN)-based procedure designated A-IS(1)-LAMP, in which an immunomagnetic separation (IMS) technique targeting as many as 69 established K antigens and a loop-mediated isothermal amplification (LAMP) assay targeting the thermostable direct hemolysin (tdh) gene were applied in an MPN format. Our IMS employed PickPen, an eight-channel intrasolution magnetic particle separation device, which enabled a straightforward microtiter plate-based IMS procedure (designated as PickPen-IMS). The ability of the procedure to quantify a wide range of tdh(+) V. parahaemolyticus levels was evaluated by testing shellfish samples in Japan and southern Thailand, where shellfish products are known to contain relatively low and high levels of total V. parahaemolyticus, respectively. The Japanese and Thai shellfish samples showed, respectively, relatively low (< 3 to 11 MPN/10 g) and considerably higher (930 to 110,000 MPN/10 g) levels of tdh(+) V. parahaemolyticus, raising concern about the safety of Thai shellfish products sold to domestic consumers at local morning markets. LAMP showed similar or higher performance than conventional PCR in the detection and quantification of a wide range of tdh(+) V. parahaemolyticus levels in shellfish products. Whereas a positive effect of PickPen-IMS was not observed in MPN determination, PickPen-IMS was able to concentrate tdh(+) V. parahaemolyticus 32-fold on average from the Japanese shellfish samples at an individual tube level, suggesting a possibility of using PickPen-IMS as an optional tool for specific shellfish samples. The A-IS(1)-LAMP procedure can be used by any health authority in the world to measure the tdh(+) V. parahaemolyticus levels in

  16. An oocyte-specific astacin family protease, alveolin, is released from cortical granules to trigger egg envelope hardening during fertilization in medaka (Oryzias latipes).

    PubMed

    Shibata, Yasushi; Iwamatsu, Takashi; Suzuki, Norio; Young, Graham; Naruse, Kiyoshi; Nagahama, Yoshitaka; Yoshikuni, Michiyasu

    2012-12-15

    It has long been hypothesized that in fishes the contents of cortical granules are involved in the hardening of egg envelope following fertilization. We previously purified the egg envelope hardening initiation factor from the exudates released from activated medaka (Oryzias latipes) eggs and tentatively termed this protein alveolin. Alveolin is a member of the astacin metalloprotease family and was proposed to be a protease which hydrolyzes ZPB at one restricted position to allow starting cross-linking with ZPC. Here, we investigated the complete pathway from biosynthesis and accumulation to secretion of alveolin. A single alveolin transcript was detected only in ovarian preparations, confirming the specific expression of alveolin in the ovary. In situ hybridization indicated that the alveolin mRNA is already expressed in the very early previtellogenic oocytes. However, immunocytochemical studies revealed that the appearance of alveolin protein was delayed until the beginning of the vitellogenic stage. The cortical granules isolated from unfertilized eggs contained a high molecular weight form of glycosylated alveolin with a 50kDa relative molecular mass. Hypotonic treatment burst isolated granules in vitro and transformed alveolin to a 21.5kDa form, which is the same size as that of natural alveolin released from eggs upon fertilization. This transformation was inhibited in the presence of leupeptin and 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF), suggesting that a serine protease is involved in alveolin activation upon fertilization. Furthermore, the phylogenetic relationship of alveolin with other vertebrate astacin family members was analyzed. The result shows that alveolin and its teleostean homologs make a new group which is separate from either the hatching enzyme, meprin and BMP1/tolloid groups.

  17. Correlation of ADCC activity with cytokine release induced by the stably expressed, glyco-engineered humanized Lewis Y-specific monoclonal antibody MB314.

    PubMed

    Kircheis, Ralf; Halanek, Nicole; Koller, Iris; Jost, Wolfgang; Schuster, Manfred; Gorr, Gilbert; Hajszan, Klaus; Nechansky, Andreas

    2012-01-01

    A major limitation to the application of therapeutic monoclonal antibodies (mAbs) is their reduced in vivo efficacy compared with the high efficacy measured in vitro. Effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) are dramatically reduced in vivo by the presence of high amounts of endogenous IgG in the serum. Recent studies have shown that modification of the glycosylation moieties attached to the Fc part of the mAb can enhance binding affinity to FcγRIIIα receptors on natural killer cells and thus may counteract the reduced in vivo efficacy. In the present study, a humanized IgG1/κ monoclonal antibody recognizing the tumor-associated carbohydrate antigen Lewis Y was stably produced in a moss expression system that allows glyco-engineering. The glyco-modified mAb (designated MB314) showed a highly homogeneous N-glycosylation pattern lacking core-fucose. A side-by-side comparison to its parental counterpart produced in conventional mammalian cell-culture (MB311, formerly known as IGN311) by fluorescence-activated cell sorting analysis confirmed that the target specificity of MB314 is similar to that of MB311. In contrast, ADCC effector function of MB314 was increased up to 40-fold whereas complement dependent cytotoxicity activity was decreased 5-fold. Notably, a release of immunostimulatory cytokines, including interferon γ, monocyte chemotactic protein-1 (MCP-1), interleukin-6 and tumor necrosis factor (TNF) was particularly induced with the glyco-modified antibody. TNF release was associated with CD14 (+) cells, indicating activation of monocytes.

  18. Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo.

    PubMed

    Sherry, B A; Alava, G; Tracey, K J; Martiney, J; Cerami, A; Slater, A F

    1995-01-01

    A characteristic feature of malaria infection is the occurrence of periodic bouts of fever. Experimental and clinical studies have strongly implicated inflammatory cytokines, like tumour necrosis factor (TNF), in the induction of these intermittent fevers [Clark et al., Infect Immunol 32:1058-1066, 1981; Clark et al., Am J Pathol 129:192-199, 1987; Karunaweera et al., Proc Natl Acad Sci USA 89:3200-3203, 1992], but the malaria-specific metabolite(s) which induce the production of such endogenous pyrogens have not yet been fully characterized. It is well known that during the course of malaria infection, a unique schizont component, alternatively referred to as "malaria pigment" or hemozoin, is released along with merozoites as the host erythrocyte bursts [Urquhart, Clin Infect Dis 19:117-131, 1994]. We have recently determined that the core structure of hemozoin comprises a novel insoluble polymer of heme units linked by iron-carboxylate bonds [Slater et al., Proc Natl Acad Sci USA 88:325-329, 1991; Slater et al., Nature 355:167-169, 1992]. We now report that purified native, as well as chemically synthesized, hemozoin crystals potently induce the release of several pyrogenic cytokines, including TNF, MIP-1 alpha, and MIP-1 beta, from murine macrophages and human peripheral blood monocytes in vitro. Also, intravenous administration of chemically synthesized preparations of hemozoin to anaesthetized rats results in a marked drop in body temperature. A similar drop in body temperature is observed following the intravenous injection of other well-characterized pyrogenic cytokines (e.g., TNF) which are known to induce a fever response in awake animals, and is thought to reflect the inability of rats to appropriately regulate their body temperature while anaesthetized. As a consequence of its ability to induce pyrogenic cytokines in vitro, and thermal dysregulation in vivo, we propose that this unique parasite metabolite is an important pyrogen released by malaria

  19. Combined antigen-specific interferon-γ and interleukin-2 release assay (FluoroSpot) for the diagnosis of Mycobacterium tuberculosis infection.

    PubMed

    Chesov, Dumitru; Lange, Christoph; Daduna, Franziska; Crudu, Valeriu; Preyer, Rosemarie; Ernst, Martin; Kalsdorf, Barbara

    2015-01-01

    To evaluate interleukin (IL)-2 and interferon (IFN)-γ secreting T-cells in parallel for the differentiation of latent infection with Mycobacterium tuberculosis infection (LTBI) from active tuberculosis. Following ex-vivo stimulation of peripheral blood mononuclear cells (PBMC) with M. tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10, immune responses were assessed by enzyme-linked immunospot IFN-γ release assay (EliSpot-IGRA) and a novel dual cytokine detecting fluorescence-linked immunospot (FluoroSpot) in 18 patients with pulmonary tuberculosis, 10 persons with previously cured tuberculosis, 25 individuals with LTBI and 16 healthy controls. Correlation of IFN-γ+ spot-forming cells in EliSpot-IGRA and FluoroSpot were R2 = 0.67 for ESAT-6 and R2 = 0.73 for CFP-10. The number of IL-2- IFN-γ+ producing cells was higher in patients with tuberculosis compared with past tuberculosis (CFP-10-induced p = 0.0068) or individuals with LTBI (ESAT-6-induced p = 0.0136). A cutoff value of >16 CFP-10-induced IFN-γ+ secreting cells/200.000 PBMC in the EliSpot-IGRA discriminated with highest sensitivity and specificity (89% and 76%, respectively). However, overlap in cytokine responses precludes distinction between the cohorts on an individual basis. Combined analysis of IFN-γ and IL-2 secretion by antigen specific T-cells does not allow a reliable differentiation between different states of M. tuberculosis infection in clinical practice.

  20. Combined Antigen-Specific Interferon-γ and Interleukin-2 Release Assay (FluoroSpot) for the Diagnosis of Mycobacterium tuberculosis Infection

    PubMed Central

    Chesov, Dumitru; Lange, Christoph; Daduna, Franziska; Crudu, Valeriu; Preyer, Rosemarie; Ernst, Martin; Kalsdorf, Barbara

    2015-01-01

    Background To evaluate interleukin (IL)-2 and interferon (IFN)-γ secreting T-cells in parallel for the differentiation of latent infection with Mycobacterium tuberculosis infection (LTBI) from active tuberculosis. Methods Following ex-vivo stimulation of peripheral blood mononuclear cells (PBMC) with M. tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10, immune responses were assessed by enzyme-linked immunospot IFN-γ release assay (EliSpot-IGRA) and a novel dual cytokine detecting fluorescence-linked immunospot (FluoroSpot) in 18 patients with pulmonary tuberculosis, 10 persons with previously cured tuberculosis, 25 individuals with LTBI and 16 healthy controls. Results Correlation of IFN- γ+ spot-forming cells in EliSpot-IGRA and FluoroSpot were R2 = 0.67 for ESAT-6 and R2 = 0.73 for CFP-10. The number of IL-2- IFN- γ+ producing cells was higher in patients with tuberculosis compared with past tuberculosis (CFP-10-induced p = 0.0068) or individuals with LTBI (ESAT-6-induced p = 0.0136). A cutoff value of >16 CFP-10-induced IFN-γ+ secreting cells/200.000 PBMC in the EliSpot-IGRA discriminated with highest sensitivity and specificity (89% and 76%, respectively). However, overlap in cytokine responses precludes distinction between the cohorts on an individual basis. Conclusions Combined analysis of IFN-γ and IL-2 secretion by antigen specific T-cells does not allow a reliable differentiation between different states of M. tuberculosis infection in clinical practice. PMID:25785445

  1. Modular Integration of Upconverting Nanocrystal-Dendrimer Composites for Folate Receptor-Specific NIR Imaging and Light-Triggered Drug Release.

    PubMed

    Wong, Pamela T; Chen, Dexin; Tang, Shengzhuang; Yanik, Sean; Payne, Michael; Mukherjee, Jhindan; Coulter, Alexa; Tang, Kenny; Tao, Ke; Sun, Kang; Baker, James R; Choi, Seok Ki

    2015-12-02

    Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system.

  2. Specific activity and activity ratios of radionuclides in soil collected about 20 km from the Fukushima Daiichi Nuclear Power Plant: Radionuclide release to the south and southwest.

    PubMed

    Tagami, Keiko; Uchida, Shigeo; Uchihori, Yukio; Ishii, Nobuyoshi; Kitamura, Hisashi; Shirakawa, Yoshiyuki

    2011-10-15

    Soil samples at different depths (0-2, 5-7 and 10-12cm) were collected from J Village, about 20km south of Fukushima Daiichi Nuclear Power Plant (FNPP) to determine their radionuclide specific activities and activity ratios. The concentrations and activity ratios of (131)I, (134, 136, 137)Cs and (129m)Te were obtained, but only trace amounts of (95)Nb, (110m)Ag and (140)La were detected which were too low to provide accurate concentrations. Radionuclides such as (95)Zr, (103, 106)Ru and (140)Ba that were found in Chernobyl fallout, were not found in these soil samples. This suggests that noble gasses and volatile radionuclides predominated in the releases from FNPP to the terrestrial environment. The average activity ratios of (131)I/(137)Cs, (134)Cs/(137)Cs, (136)Cs/(137)Cs and (129m)Te/(137)Cs were 55, 0.90, 0.22 and 4.0 (corrected to March 11, 2011) in the 0-2cm soil samples of April 20 and 28, 2011.

  3. Mental Health Evaluations for Adolescents Prior to Bariatric Surgery: A Review of Existing Practices and a Specific Example of Assessment Procedures.

    PubMed

    Sysko, Robyn; Zandberg, Laurie J; Devlin, Michael J; Annunziato, Rachel A; Zitsman, Jeffrey L; Walsh, B Timothy

    2013-06-01

    Best practice guidelines for adolescents considering bariatric surgery recommend a pre-operative mental health evaluation. However, only general information about these assessments appears in the literature, which makes consistency of administration challenging. This review proposes a specific empirically-derived format for pre-surgical mental health evaluations and summarizes currently available data on the psychiatric functioning of adolescents seeking bariatric surgery. Studies of mental health evaluations for adults preparing for bariatric surgery are reviewed, as is the limited literature relevant to adolescent evaluations. A specific and detailed example of an evaluation (clinical interview, self-report questionnaires, cognitive assessment) used for younger patients at a major metropolitan hospital center is presented, followed by data from an initial group of adolescents completing this evaluation. 200 adolescents (n=139 female; age: 14-18 y, BMI: 35.4-83.3 kg/m(2)) presenting for bariatric surgery. A notable subset of adolescents reported current Axis I conditions (31.5%) and current mental health treatment (29.5%), but reports of current illicit drug use (1.5%) and regular alcohol use (0.5%) were relatively rare. Procedures for using the completed evaluation and post-surgery monitoring of psychosocial issues are discussed. Adolescents considering weight loss surgery should receive comprehensive pre-surgical mental health evaluations, but additional data are needed to develop specific recommendations the use of these evaluations in post-operative care.

  4. Mental Health Evaluations for Adolescents Prior to Bariatric Surgery: A Review of Existing Practices and a Specific Example of Assessment Procedures

    PubMed Central

    Sysko, Robyn; Zandberg, Laurie J.; Devlin, Michael J.; Annunziato, Rachel A.; Zitsman, Jeffrey L.; Walsh, B. Timothy

    2013-01-01

    Objective Best practice guidelines for adolescents considering bariatric surgery recommend a pre-operative mental health evaluation. However, only general information about these assessments appears in the literature, which makes consistency of administration challenging. This review proposes a specific empirically-derived format for pre-surgical mental health evaluations and summarizes currently available data on the psychiatric functioning of adolescents seeking bariatric surgery. Design Studies of mental health evaluations for adults preparing for bariatric surgery are reviewed, as is the limited literature relevant to adolescent evaluations. A specific and detailed example of an evaluation (clinical interview, self-report questionnaires, cognitive assessment) used for younger patients at a major metropolitan hospital center is presented, followed by data from an initial group of adolescents completing this evaluation. Subjects 200 adolescents (n=139 female; age: 14–18 y, BMI: 35.4–83.3 kg/m2) presenting for bariatric surgery. Results A notable subset of adolescents reported current Axis I conditions (31.5%) and current mental health treatment (29.5%), but reports of current illicit drug use (1.5%) and regular alcohol use (0.5%) were relatively rare. Procedures for using the completed evaluation and post-surgery monitoring of psychosocial issues are discussed. Conclusions Adolescents considering weight loss surgery should receive comprehensive pre-surgical mental health evaluations, but additional data are needed to develop specific recommendations the use of these evaluations in post-operative care. PMID:24073019

  5. Cell-type specific deletion of GABA(A)α1 in corticotropin-releasing factor-containing neurons enhances anxiety and disrupts fear extinction.

    PubMed

    Gafford, Georgette M; Guo, Ji-Dong; Flandreau, Elizabeth I; Hazra, Rimi; Rainnie, Donald G; Ressler, Kerry J

    2012-10-02

    Corticotropin-releasing factor (CRF) is critical for the endocrine, autonomic, and behavioral responses to stressors, and it has been shown to modulate fear and anxiety. The CRF receptor is widely expressed across a variety of cell types, impeding progress toward understanding the contribution of specific CRF-containing neurons to fear dysregulation. We used a unique CRF-Cre driver transgenic mouse line to remove floxed GABA(A)α1 subunits specifically from CRF neurons [CRF-GABA(A)α1 KO]. This process resulted in mice with decreased GABA(A)α1 expression only in CRF neurons and increased CRF mRNA within the amygdala, bed nucleus of the stria terminalis (BNST) and paraventricular nucleus of the hypothalamus. These mice show normal locomotor and pain responses and no difference in depressive-like behavior or Pavlovian fear conditioning. However, CRF-GABA(A)α1 KO increased anxiety-like behavior and impaired extinction of conditioned fear, coincident with an increase in plasma corticosterone concentration. These behavioral impairments were rescued with systemic or BNST infusion of the CRF antagonist R121919. Infusion of Zolpidem, a GABA(A)α1-preferring benzodiazepine-site agonist, into the BNST of the CRF-GABA(A)α1 KO was ineffective at decreasing anxiety. Electrophysiological findings suggest a disruption in inhibitory current may play a role in these changes. These data indicate that disturbance of CRF containing GABA(A)α1 neurons causes increased anxiety and impaired fear extinction, both of which are symptoms diagnostic for anxiety disorders, such as posttraumatic stress disorder.

  6. Cell-free Protein Synthesis from a Release Factor 1 Deficient Escherichia coli Activates Efficient and Multiple Site-specific Nonstandard Amino Acid Incorporation

    PubMed Central

    2014-01-01

    Site-specific incorporation of nonstandard amino acids (NSAAs) into proteins enables the creation of biopolymers, proteins, and enzymes with new chemical properties, new structures, and new functions. To achieve this, amber (TAG codon) suppression has been widely applied. However, the suppression efficiency is limited due to the competition with translation termination by release factor 1 (RF1), which leads to truncated products. Recently, we constructed a genomically recoded Escherichia coli strain lacking RF1 where 13 occurrences of the amber stop codon have been reassigned to the synonymous TAA codon (rEc.E13.ΔprfA). Here, we assessed and characterized cell-free protein synthesis (CFPS) in crude S30 cell lysates derived from this strain. We observed the synthesis of 190 ± 20 μg/mL of modified soluble superfolder green fluorescent protein (sfGFP) containing a single p-propargyloxy-l-phenylalanine (pPaF) or p-acetyl-l-phenylalanine. As compared to the parent rEc.E13 strain with RF1, this results in a modified sfGFP synthesis improvement of more than 250%. Beyond introducing a single NSAA, we further demonstrated benefits of CFPS from the RF1-deficient strains for incorporating pPaF at two- and five-sites per sfGFP protein. Finally, we compared our crude S30 extract system to the PURE translation system lacking RF1. We observed that our S30 extract based approach is more cost-effective and high yielding than the PURE translation system lacking RF1, ∼1000 times on a milligram protein produced/$ basis. Looking forward, using RF1-deficient strains for extract-based CFPS will aid in the synthesis of proteins and biopolymers with site-specifically incorporated NSAAs. PMID:24328168

  7. Identifying Centers of Excellence in Efficiency and Quality in coronary revascularization: an exploratory approach for procedure-specific value-based purchasing program design.

    PubMed

    Saleh, Shadi S; Hannan, Edward; Racz, Mike

    2008-01-01

    The advent of the value-based purchasing (VBP) concept in which efficiency and quality are considered prompted an interest in exploring approaches that incorporate both. This study examined a hospital classification method, Centers for Excellence in Efficiency and Quality (CEEQs), for coronary revascularization procedures. The results identified select hospitals (two [out of 33] in coronary artery bypass graft surgery (CABG) and seven in percutaneous coronary intervention (PCI)) that can be classified as CEEQs. Furthermore, an investigation of hospitals' efficiency and quality revealed great variation in efficiency among high-quality hospitals. The study demonstrated the possibility of employing service- or disease-specific approaches to VBP and pay-for-performance (P4P) programs.

  8. Development of an integrated procedure for the detection of central nervous tissue in meat products using cholesterol and neuron-specific enolase as markers.

    PubMed

    Lücker, E; Eigenbrodt, E; Wenisch, S; Failing, K; Leiser, R; Bülte, M

    1999-03-01

    The emergence of a new variant of Creutzfeldt-Jakob disease during the bovine spongiform encephalopathy epidemic has focused attention on the use of tissue from the central nervous system (CNS) in food. So far, the banning of CNS tissue could not be effectively controlled because procedures for detection were missing. With regard to preventive health protection and labeling law enforcement, we have developed an integrated procedure for the detection of CNS tissue in meat products. Herein, we show that antigenic characteristics of neuron-specific enolase (NSE) quantitatively survive technological treatment including severe homogenization and pressure heating. Using both poly- and monoclonal antibodies against NSE in the Western blot, bovine and porcine brain could be detected in sausages, albeit with varying sensitivity (1 to 4%). Sensitivity was increased after reduction of fat content (30 to 40%) of the samples by means of a soxhlet extraction. This made possible the detection of brain addition as low as 0.25% when using monoclonal antibodies. Immunohistology showed distribution of CNS tissue in heat-treated meat products to be homogeneous. Immunoreaction was not found to be bound to morphologically intact histological or cytological structures; however, it proved to be highly specific. The quantification of cholesterol provides a low-cost screening method for the rapid identification of meat products, suspicious with regard to CNS tissue addition. Cholesterol content increased by 26 mg per 100 g of fresh substance for each percentage of brain added to internally produced reference material. Using three different approaches (internal reference material, raw material, and field samples), a provisional cutoff point of normal cholesterol content was calculated for emulsion-type cooked sausages to be 115 mg/100 g (P < 0.05).

  9. Specific functions of the Rep and Rep' proteins of porcine circovirus during copy-release and rolling-circle DNA replication

    USDA-ARS?s Scientific Manuscript database

    The roles of two porcine circovirus replication initiator proteins, Rep and Rep', in generating copy-release and rolling-circle DNA replication intermediates were determined. Rep uses the supercoiled closed-circular genome (ccc) to initiate leading-strand synthesis (identical to copy-release replica...

  10. Long-term plasticity of corticostriatal synapses is modulated by pathway-specific co-release of opioids through κ-opioid receptors.

    PubMed

    Hawes, Sarah L; Salinas, Armando G; Lovinger, David M; Blackwell, Kim T

    2017-08-15

    Both endogenous opioids and opiate drugs of abuse modulate learning of habitual and goal-directed actions, and can also modify long-term plasticity of corticostriatal synapses. Striatal projection neurons of the direct pathway co-release the opioid neuropeptide dynorphin which can inhibit dopamine release via κ-opioid receptors. Theta-burst stimulation of corticostriatal fibres produces long-term potentiation (LTP) in striatal projection neurons when measured using whole-cell patch recording. Optogenetic activation of direct pathway striatal projection neurons inhibits LTP while reducing dopamine release. Because the endogenous release of opioids is activity dependent, this modulation of synaptic plasticity represents a negative feedback mechanism that may limit runaway enhancement of striatal neuron activity in response to drugs of abuse. Synaptic plasticity in the striatum adjusts behaviour adaptively during skill learning, or maladaptively in the case of addiction. Just as dopamine plays a critical role in synaptic plasticity underlying normal skill learning and addiction, endogenous and exogenous opiates also modulate learning and addiction-related striatal plasticity. Though the role of opioid receptors in long-term depression in striatum has been characterized, their effect on long-term potentiation (LTP) remains unknown. In particular, direct pathway (dopamine D1 receptor-containing; D1R-) spiny projection neurons (SPNs) co-release the opioid neuropeptide dynorphin, which acts at presynaptic κ-opioid receptors (KORs) on dopaminergic afferents and can negatively regulate dopamine release. Therefore, we evaluated the interaction of co-released dynorphin and KOR on striatal LTP. We optogenetically facilitate the release of endogenous dynorphin from D1R-SPNs in brain slice while using whole-cell patch recording to measure changes in the synaptic response of SPNs following theta-burst stimulation (TBS) of cortical afferents. Our results demonstrate that TBS

  11. Computational replication of the patient-specific stenting procedure for coronary artery bifurcations: From OCT and CT imaging to structural and hemodynamics analyses.

    PubMed

    Chiastra, Claudio; Wu, Wei; Dickerhoff, Benjamin; Aleiou, Ali; Dubini, Gabriele; Otake, Hiromasa; Migliavacca, Francesco; LaDisa, John F

    2016-07-26

    The optimal stenting technique for coronary artery bifurcations is still debated. With additional advances computational simulations can soon be used to compare stent designs or strategies based on verified structural and hemodynamics results in order to identify the optimal solution for each individual's anatomy. In this study, patient-specific simulations of stent deployment were performed for 2 cases to replicate the complete procedure conducted by interventional cardiologists. Subsequent computational fluid dynamics (CFD) analyses were conducted to quantify hemodynamic quantities linked to restenosis. Patient-specific pre-operative models of coronary bifurcations were reconstructed from CT angiography and optical coherence tomography (OCT). Plaque location and composition were estimated from OCT and assigned to models, and structural simulations were performed in Abaqus. Artery geometries after virtual stent expansion of Xience Prime or Nobori stents created in SolidWorks were compared to post-operative geometry from OCT and CT before being extracted and used for CFD simulations in SimVascular. Inflow boundary conditions based on body surface area, and downstream vascular resistances and capacitances were applied at branches to mimic physiology. Artery geometries obtained after virtual expansion were in good agreement with those reconstructed from patient images. Quantitative comparison of the distance between reconstructed and post-stent geometries revealed a maximum difference in area of 20.4%. Adverse indices of wall shear stress were more pronounced for thicker Nobori stents in both patients. These findings verify structural analyses of stent expansion, introduce a workflow to combine software packages for solid and fluid mechanics analysis, and underscore important stent design features from prior idealized studies. The proposed approach may ultimately be useful in determining an optimal choice of stent and position for each patient.

  12. Serum levels of prostate-specific antigen and androgens after nasal administration of a gonadotropin releasing hormone-agonist in hirsute women.

    PubMed

    Kocak, Muberra; Tarcan, Aytül; Beydilli, Gülay; Koç, Sevgi; Haberal, Ali

    2004-04-01

    We aimed to determine whether ovarian suppression affects the production rate of prostate-specific antigen (PSA) in hirsute women. A total of 34 hirsute women who had a modified Ferriman-Gallwey (FG) score of > or = 7 and 14, non-hirsute women as the control group were recruited for this prospective controlled study. Serum samples for evaluation of basal hormones and PSA concentration were collected and were analyzed by commercial kits and chemiluminescent enzyme immunoassay. The hirsute women were given 400 microg/day nafarelin acetate for 3 months. Basal hormones, PSA levels and FG scores were then assessed. ANOVA and Tukey test were used to compare differences in means between the hirsute and the non-hirsute group at the beginning of the study. Student's t test, Tukey test and repeated measures variance analysis were used to evaluate differences in the study group and between the women with polycystic ovary syndrome (PCOS) and idiopathic hirsutism after gonadotropin releasing hormone (GnRH)-agonist administration. Statistical significance was assumed with a value of p < 0.05. PCOS and idiopathic hirsutism were diagnosed in 58.8% and 41.2% of 34 hirsute women, respectively. Age and body mass index (BMI) were similar in the hirsute and the control group (p > 0.05). FG scores in the PCOS group (20.3 +/- 1.7) were statistically similar to those of the group with idiopathic hirsutism (17.6 +/- 1.7) (p > 0.05). The non-hirsute women had significantly lower serum PSA concentrations than the hirsute group (p < 0.001). The basal mean level of PSA was 0.095 +/- 0.001 in the PCOS, 0.0061 +/- 0.009 in the idiopathic hirsute and 0.0040 +/- 0.004 ng/ml in the control group. No significant difference in the mean PSA levels was noted between the PCOS and the idiopathic hirsute subgroups before and after GnRH agonist treatment (0.0096 +/- 0.01 and 0.0051 +/- 0.032 ng/ml, respectively) (p > 0.05). FG scores, testosterone, 17alpha-hydroxyprogesterone and dehydroepiandrosterone

  13. A 12-year experience using the Brown two-portal endoscopic procedure of transverse carpal ligament release in 14,722 patients: defining a new paradigm in the treatment of carpal tunnel syndrome.

    PubMed

    Hankins, Christopher L; Brown, Michael G; Lopez, Randolph A; Lee, Andrew K; Dang, Joseph; Harper, R Douglas

    2007-12-01

    Compared with the open technique, endoscopic carpal tunnel release has a shorter postoperative recovery period but has been associated with an increased risk of iatrogenic injury. Because of morbidity of the open method, including painful scars, pillar pain, tendon adhesions, scar entrapment of the median nerve, chronic regional pain syndrome, and a longer postoperative recovery period, many patients have been treated nonoperatively to circumvent or forestall surgery, resulting in unrelieved median nerve compression and an increased risk of permanent nerve injury. Inclusion criteria included a diagnosis of carpal tunnel syndrome based on history and physical examination and electrodiagnostic studies; failure of a short trial of conservative therapy; and advanced disease as evidenced by sensory, motor, or atrophic changes in the median nerve distribution. Exclusion criteria included prior surgery, wrist extension of less [corrected] than 40 degrees, mass within the carpal tunnel, Guyon's syndrome, and bony carpal tunnel abnormalities. Patients meeting these criteria were treated by the Brown two-portal endoscopic technique. A total of 14,722 patients were treated with the Brown endoscopic procedure. Eleven patients (0.07 percent) required conversion to an open procedure. There was one iatrogenic injury. Postoperative results were inversely related to the severity of the preoperative electrodiagnostic studies and the duration of symptoms regardless of the method of nonoperative treatment given. Operative decompression should be carried out promptly if symptoms have been present for 2 months or longer, as the occurrence of permanent nerve damage has been noted within this time frame. The authors advocate use of the two-portal endoscopic technique as previously described by Brown et al. for this purpose.

  14. Dose- and tissue-specific interaction of monoterpenes with the gibberellin-mediated release of potato tuber bud dormancy, sprout growth and induction of α-amylases and β-amylases.

    PubMed

    Rentzsch, Sonja; Podzimska, Dagmara; Voegele, Antje; Imbeck, Madeleine; Müller, Kerstin; Linkies, Ada; Leubner-Metzger, Gerhard

    2012-01-01

    Gibberellins (GA) are involved in bud dormancy release in several species. We show here that GA-treatment released bud dormancy, initiated bud sprouting and promoted sprout growth of excised potato tuber bud discs ('eyes'). Monoterpenes from peppermint oil (PMO) and S-(+)-carvone (CAR) interact with the GA-mediated bud dormancy release in a hormesis-type response: low monoterpene concentrations enhance dormancy release and the initiation of bud sprouting, whereas high concentrations inhibit it. PMO and CAR did, however, not affect sprout growth rate after its onset. We further show that GA-induced dormancy release is associated with tissue-specific regulation of α- and β-amylases. Molecular phylogenetic analysis shows that potato α-amylases cluster into two distinct groups: α-AMY1 and α-AMY2. GA-treatment induced transcript accumulation of members of both α-amylase groups, as well as α- and β-amylase enzyme activity in sprout and 'sub-eye' tissues. In sprouts, CAR interacts with the GA-mediated accumulation of α-amylase transcripts in an α-AMY2-specific and dose-dependent manner. Low CAR concentrations enhance the accumulation of α-AMY2-type α-amylase transcripts, but do not affect the α-AMY1-type transcripts. Low CAR concentrations also enhance the accumulation of α- and β-amylase enzyme activity in sprouts, but not in 'sub-eye' tissues. In contrast, high CAR concentrations have no appreciable effect in sprouts on the enzyme activities and the α-amylase transcript abundances of either group. The dose-dependent effects on the enzyme activities and the α-AMY2-type α-amylase transcripts in sprouts are specific for CAR but not for PMO. Different monoterpenes therefore may have specific targets for their interaction with hormone signalling pathways.

  15. High-Throughput and Quantitative Procedure for Determining Sources of Escherichia coli in Waterways by Using Host-Specific DNA Marker Genes▿

    PubMed Central

    Yan, Tao; Hamilton, Matthew J.; Sadowsky, Michael J.

    2007-01-01

    Escherichia coli is currently used as an indicator of fecal pollution and to assess water quality. While several genotypic techniques have been used to determine potential sources of fecal bacteria impacting waterways and beaches, they do not allow for the rapid analysis of a large number of samples in a relatively short period of time. Here we report that gene probes identified by Hamilton and colleagues (M. J. Hamilton, T. Yan, and M. J. Sadowsky, Appl. Environ. Microbiol. 72:4012-4019, 2006) were useful for the development of a high-throughput and quantitative macroarray hybridization system to determine numbers of E. coli bacteria originating from geese/ducks. The procedure we developed, using a QBot robot for picking and arraying of colonies, allowed us to simultaneously analyze up to 20,736 E. coli colonies from water samples, with minimal time and human input. Statistically significant results were obtained by analyzing 700 E. coli colonies per water sample, allowing for the analysis of approximately 30 sites per macroarray. Macroarray hybridization studies done on E. coli collected from water samples obtained from two urban Minnesota lakes and one rural South Carolina lake indicated that geese/ducks contributed up to 51% of the fecal bacteria in the urban lake water samples, and the level was below the detection limit in the rural lake water sample. This technique, coupled with the use of other host source-specific gene probes, holds great promise as a new quantitative microbial source tracking tool to rapidly determine the origins of E. coli in waterways and on beaches. PMID:17158618

  16. Tissue-specific effects of in vitro fertilization procedures on genomic cytosine methylation levels in overgrown and normal sized bovine fetuses.

    PubMed

    Hiendleder, Stefan; Wirtz, Michaela; Mund, Cora; Klempt, Martina; Reichenbach, Horst-Dieter; Stojkovic, Miodrag; Weppert, Myriam; Wenigerkind, Hendrik; Elmlinger, Martin; Lyko, Frank; Schmitz, Oliver J; Wolf, Eckhard

    2006-07-01

    Epigenetic perturbations are assumed to be responsible for phenotypic abnormalities of fetuses and offspring originating from in vitro embryo techniques. We studied 29 viable Day-80 bovine fetuses to assess the effects of two in vitro fertilization protocols (IVF1 and IVF2) on fetal phenotype and genomic cytosine methylation levels in liver, skeletal muscle, and brain. The IVF1 protocol employed 0.01 U/ml of FSH and LH in oocyte maturation medium and 5% estrous cow serum (ECS) in embryo culture medium, whereas the IVF2 protocol employed 0.2 U/ml of FSH and no LH for oocyte maturation and 10% ECS for embryo culture. Comparisons with in vivo-fertilized controls (n=14) indicated an apparently normal phenotype for IVF1 fetuses (n=5), but IVF2 fetuses (n=10) were significantly heavier (19.9%) and longer (4.7%), with increased heart (25.2%) and liver (27.9%) weights, and thus displayed an overgrowth phenotype. A clinicochemical screen of 18 plasma parameters revealed significantly increased levels of insulin-like growth factor 1 (40.8%) and creatinine (37.5%) in IVF2, but not in IVF1, fetuses. Quantification of genomic 5-methylcytosine (5mC) by capillary electrophoresis indicated that both IVF1 and IVF2 fetuses differed from controls. We observed significant DNA hypomethylation in liver and muscle of IVF1 fetuses (-16.1% and -9.3%, respectively) and significant hypermethylation in liver of IVF2 fetuses (+11.2%). The 5mC level of cerebral DNA was not affected by IVF protocol. Our data indicate that bovine IVF procedures can affect fetal genomic 5mC levels in a protocol- and tissue-specific manner and show that hepatic hypermethylation is associated with fetal overgrowth and its correlated endocrine changes.

  17. Trials based on specific fracture configuration and surgical procedures likely to be more relevant for decision making in the management of fractures of the proximal humerus

    PubMed Central

    Patel, N. K.; Griffiths, D.; Athanasiou, T.; Gupte, C. M.; Reilly, P.

    2016-01-01

    . Griffiths, T. Athanasiou, C. M. Gupte, P. Reilly. Trials based on specific fracture configuration and surgical procedures likely to be more relevant for decision making in the management of fractures of the proximal humerus: Findings of a meta-analysisBone Joint Res 2016;5:470–480. DOI: 10.1302/2046-3758.510.2000638. PMID:27756738

  18. 28 CFR 572.31 - Procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE PAROLE Parole and Mandatory Release Violator Reports § 572.31 Procedures. Staff shall prepare the Violator... and district; (b) Description of release procedure; (c) Alleged violation(s) of parole or...

  19. 28 CFR 572.31 - Procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE PAROLE Parole and Mandatory Release Violator Reports § 572.31 Procedures. Staff shall prepare the Violator... and district; (b) Description of release procedure; (c) Alleged violation(s) of parole or...

  20. 28 CFR 572.31 - Procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE PAROLE Parole and Mandatory Release Violator Reports § 572.31 Procedures. Staff shall prepare the Violator... and district; (b) Description of release procedure; (c) Alleged violation(s) of parole or...

  1. 28 CFR 572.31 - Procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE PAROLE Parole and Mandatory Release Violator Reports § 572.31 Procedures. Staff shall prepare the Violator... and district; (b) Description of release procedure; (c) Alleged violation(s) of parole or...

  2. 28 CFR 572.31 - Procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE PAROLE Parole and Mandatory Release Violator Reports § 572.31 Procedures. Staff shall prepare the Violator... and district; (b) Description of release procedure; (c) Alleged violation(s) of parole or...

  3. Evaluation of a soil incubation method to characterize nitrogen release patterns of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry B; Obreza, Thomas A; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release patterns of slow-release fertilizers (SRF) and controlled-release fertilizers (CRF) during the last few decades. These technologies have been developed mainly by manufacturers, and are product-specific, based on the regulation and analysis of each SRF and CRF product. Despite previous efforts to characterize SRF and CRF materials, no standardized, validated method exists to assess their nutrient release patterns. However, the increased production and distribution of these materials in specialty and nonspecialty markets requires an appropriate method to verify product claims and material performance. A soil incubation column leaching procedure was evaluated to determine its suitability as a standard method to estimate nitrogen (N) release patterns of SRFs and CRFs during 180 days. The influence of three soil/sand ratios, three incubation temperatures, and four soils on method behavior was assessed using five SRFs and three CRFs. In general, the highest soil/sand ratio increased the N release rate of all materials, but this effect was more marked for the SRFs. Temperature had the greatest influence on N release rates. For CRFs, the initial N release rates and the percentage N released/day increased as temperature increased. For SRFs, raising the temperature from 25 to 35 degreesC increased initial N release rate and the total cumulative N released, and almost doubled the percentage released/day. The percentage N released/day from all products generally increased as the texture of the soil changed from sandy to loamy (lowa>California>Pennsylvania>Florida). The soil incubation technique was demonstrated to be robust and reliable for characterizing N release patterns from SRFs and CRFs. The method was reproducible, and variations in soil/sand ratio, temperature, and soil had little effect on the results.

  4. Specific functions of the Rep and Rep׳ proteins of porcine circovirus during copy-release and rolling-circle DNA replication.

    PubMed

    Cheung, Andrew K

    2015-07-01

    The roles of two porcine circovirus replication initiator proteins, Rep and Rep׳, in generating copy-release and rolling-circle DNA replication intermediates were determined. Rep uses the supercoiled closed-circular genome (ccc) to initiate leading-strand synthesis (identical to copy-release replication) and generates the single-stranded circular (ssc) genome from the displaced DNA strand. In the process, a minus-genome primer (MGP) necessary for complementary-strand synthesis, from ssc to ccc, is synthesized. Rep׳ cleaves the growing nascent-strand to regenerate the parent ccc molecule. In the process, a Rep׳-DNA hybrid containing the right palindromic sequence (at the origin of DNA replication) is generated. Analysis of the virus particle showed that it is composed of four components: ssc, MGP, capsid protein and a novel Rep-related protein (designated Protein-3).

  5. A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media.

    PubMed

    Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

    2016-01-01

    The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials' community by elucidating an easier assay for colonic drug delivery.

  6. A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media

    PubMed Central

    Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

    2016-01-01

    The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade “A” honey. Approximately 1010–1011 colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials’ community by elucidating an easier assay for colonic drug delivery. PMID:27051284

  7. Target-specific near-IR induced drug release and photothermal therapy with accumulated Au/Ag hollow nanoshells on pulmonary cancer cell membranes.

    PubMed

    Noh, Mi Suk; Lee, Somin; Kang, Homan; Yang, Jin-Kyoung; Lee, Hyunmi; Hwang, Doyk; Lee, Jong Woo; Jeong, Sinyoung; Jang, Yoonjeong; Jun, Bong-Hyun; Jeong, Dae Hong; Kim, Seong Keun; Lee, Yoon-Sik; Cho, Myung-Haing

    2015-03-01

    Au/Ag hollow nanoshells (AuHNSs) were developed as multifunctional therapeutic agents for effective, targeted, photothermally induced drug delivery under near-infrared (NIR) light. AuHNSs were synthesized by galvanic replacement reaction. We further conjugated antibodies against the epidermal growth factor receptor (EGFR) to the PEGylated AuHNS, followed by loading with the antitumor drug doxorubicin (AuHNS-EGFR-DOX) for lung cancer treatment. AuHNSs showed similar photothermal efficiency to gold nanorods under optimized NIR laser power. The targeting of AuHNS-EGFR-DOX was confirmed by light-scattering images of A549 cells, and doxorubicin release from the AuHNSs was evaluated under low pH and NIR-irradiated conditions. Multifunctional AuHNS-EGFR-DOX induced photothermal ablation of the targeted lung cancer cells and rapid doxorubicin release following irradiation with NIR laser. Furthermore, we evaluated the effectiveness of AuHNS-EGFR-DOX drug delivery by comparing two drug delivery methods: receptor-mediated endocytosis and cell-surface targeting. Accumulation of the AuHNS-EGFR-DOX on the cell surfaces by targeting EGFR turned out to be more effective for lung cancer treatments than uptake of AuHNS-EGFR-DOX. Taken together, our data suggest a new and optimal method of NIR-induced drug release via the accumulation of targeted AuHNS-EGFR-DOX on cancer cell membranes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Designing Flightdeck Procedures

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Mauro, Robert; Degani, Asaf; Loukopoulou, Loukia

    2016-01-01

    The primary goal of this document is to provide guidance on how to design, implement, and evaluate flight deck procedures. It provides a process for developing procedures that meet clear and specific requirements. This document provides a brief overview of: 1) the requirements for procedures, 2) a process for the design of procedures, and 3) a process for the design of checklists. The brief overview is followed by amplified procedures that follow the above steps and provide details for the proper design, implementation and evaluation of good flight deck procedures and checklists.

  9. A STUDY TO DETERMINE SPECIFIC SOURCES OF RESISTANCE TO THE USE OF AUDIOVISUAL MATERIALS BY COLLEGE AND UNIVERSITY TEACHERS AND THE DEVELOPMENT OF PROCEDURES FOR OVERCOMING THE BARRIERS TO OPTIMUM USE.

    ERIC Educational Resources Information Center

    BROWN, ROBERT M.; MCINTYRE, KENNETH

    THE OBJECTIVES OF THIS STUDY WERE TO (1) DETERMINE THE EXTENT OF USE OF AUDIOVISUAL MATERIALS BY THE FACULTY, (2) IDENTIFY SPECIFIC SOURCES OF RESISTANCE TO THE USE OF AUDIOVISUAL MATERIALS, (3) STUDY AND ASSEMBLE INFORMATION ON AUDIOVISUAL FACILITIES AND PROCEDURES WHICH WOULD BE CONDUCIVE TO THE IMPROVEMENT OF COLLEGE TEACHING, AND (4) DEVELOP…

  10. Historical Doses from Tritiated Water and Tritiated Hydrogen Gas Released to the Atmosphere from Lawrence Livermore National Laboratory (LLNL). Part 2. LLNL Annual Site-specific Data, 1953 - 2003

    SciTech Connect

    Peterson, S R

    2005-03-07

    It is planned to use the tritium dose model, DCART (Doses from Chronic Atmospheric Releases of Tritium), to reconstruct dose to the hypothetical maximally exposed individual from annual routine releases of tritiated water (HTO) and tritiated hydrogen gas (HT) from all Lawrence Livermore National Laboratory (LLNL) facilities and from the Sandia National (SNL) Laboratory's Tritium Research Laboratory over the last fifty years. DCART has been described in Part 1 of ''Historical Doses From Tritiated Water And Tritiated Hydrogen Gas Released To The Atmosphere from Lawrence Livermore National Laboratory (LLNL)'' (UCRL-TR-205083). This report (Part 2) summarizes information about annual routine releases of tritium from LLNL (and SNL) since 1953. Historical records were used to derive facility-specific annual data (e.g., source terms, dilution factors, ambient air concentrations, meteorological data, including absolute humidity and rainfall, etc.) and their associated uncertainty distributions. These data will be used as input to DCART to calculate annual dose for each year of LLNL operations. Sources of information are carefully referenced, and assumptions are documented. Confidence on all data post-1974 is quite high. Prior to that, further adjustment to the estimated uncertainty may have to be made if more information comes to light.

  11. A COMPARISON OF THE SPECIFICITY OF INHIBITION BY PHOSPHONATE ESTERS OF THE FIRST COMPONENT OF COMPLEMENT AND THE ANTIGEN-INDUCED RELEASE OF HISTAMINE FROM GUINEA PIG LUNG

    PubMed Central

    Becker, Elmer L.; Austen, K. Frank

    1964-01-01

    The ability of a number p-nitrophenylethyl alkyl, phenyl alkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the activated first component (C'1a) of guinea pig complement, and the antigen-induced release of histamine from sliced, perfused guinea pig lung has been compared. C'1a in its reactivity with these phosphonates is distinctly more similar to trypsin than to any of the other enzymes studied previously. It is suggested that both trypsin and C'1a possess an anionic group in the active center of the respective enzyme, but the distance between the anionic and esteratic site in C'1a might be less than in trypsin. The pattern of inhibition of histamine relase by the alkyl, phenyl alkyl, and chloroalkyl phosphonates is similar to the inhibition of C'1a by these compounds, although distinct differences are apparent. The aminoalkyl phosphonates are distinctly less active inhibitors of histamine release than the corresponding alkyl phosphonates, whereas the reverse is true of the inhibition of C'1a. On the basis of these differences, it is tentatively concluded that the organophosphorus-inhibitable enzymes in the guinea pig systems studied here are similar but not identical. PMID:14212115

  12. Comparison of plasma exchange performances between Spectra Optia and COBE Spectra apheresis systems in repeated procedures considering variability and using specific statistical models.

    PubMed

    Hequet, O; Stocco, V; Assari, S; Drillat, P; Le, Q H; Kassir, A; Rigal, D; Bouzgarrou, R

    2014-08-01

    Repeated therapeutic plasma exchange (TPE) procedures using centrifugation techniques became a standard therapy in some diseases. As the new device Spectra Optia (SPO; Terumo BCT) was available, we studied its performances in repeated procedures in 20 patients in three apheresis units. First we analysed the performance results obtained by SPO. Second we compared the performances of the SPO device to a standard device, COBE Spectra (CSP; Terumo BCT) in the same patients using statistical method of mixed effects linear regression that considers variability between patients, centres and apheresis procedures. The performances analysed were classified according to plasma removal performances and their consequences on patients whose blood disturbances were assessed. Primary outcome was plasma removal efficiency (PRE) and PRE-anticoagulant corrected which was a more accurate parameter. Secondary outcomes corresponded to the volume of ACD-A consumed, platelets content in waste bag, procedure duration and status of coagulation system observed after TPE sessions. Before comparing the performances of both devices we compared the plasma volumes (PVs) processed in both techniques which showed that the PVs processed in SPO procedures were lower than in CSP procedures. In these conditions the statistical analysis revealed similar performances in both apheresis devices in PRE (p = ns) but better performances with SPO when considering higher PRE corrected by anticoagulant volume used (p < 0.05). Comparison of secondary outcomes showed no difference after SPO and CSP. After verifying that pre-apheresis patients' coagulation blood levels were identical before SPO and CSP, we showed identical haemostasis disturbances after SPO and CSP but lower platelet losses and higher fibrinogen post-apheresis blood levels after SPO (p < 0.05). No side effects or technical complications occurred during and after SPO and CSP. This study demonstrated that the Spectra Optia device is an

  13. Historical Doses from Tritiated Water and Tritiated Hydrogen Gas Released to the Atmosphere from Lawrence Livermore National Laboratory (LLNL). Part 2. LLNL Annual Site-specific Data, 1953 - 2005

    SciTech Connect

    Peterson, S

    2007-08-15

    Historical information about tritium released routinely and accidentally from all Livermore Site Lawrence Livermore National Laboratory (LLNL) facilities and from the Tritium Research Laboratory of Sandia National Laboratories/California (SNL/CA) between 1953 through 2005 has been compiled and summarized in this report. Facility-specific data (annual release rates and dilution factors) have been derived from the historical information. These facility-specific data are needed to calculate annual doses to a hypothetical site-wide maximally exposed individual from routine releases of tritiated water (HTO) and tritiated hydrogen gas (HT) to the atmosphere. Doses can also be calculated from observed air tritium concentrations, and mean annual values for one air tritium sampling location are presented. Other historical data relevant to a dose reconstruction (e.g., meteorological data, including absolute humidity and rainfall) are also presented. Sources of information are carefully referenced, and assumptions are documented. Uncertainty distributions have been estimated for all parameter values. Confidence in data post-1974 is high.

  14. Rad-Release

    ScienceCinema

    None

    2016-07-12

    The R&D 100 Award winning Rad-Release Chemical Decontamination Technology is a highly effective (up to 99% removal rate), affordable, patented chemical-foam-clay decontamination process tailored to specific radiological and metal contaminants, which is applicable to a wide variety of substrates. For more information about this project, visit http://www.inl.gov/rd100/2011/rad-release/

  15. Rad-Release

    SciTech Connect

    2011-01-01

    The R&D 100 Award winning Rad-Release Chemical Decontamination Technology is a highly effective (up to 99% removal rate), affordable, patented chemical-foam-clay decontamination process tailored to specific radiological and metal contaminants, which is applicable to a wide variety of substrates. For more information about this project, visit http://www.inl.gov/rd100/2011/rad-release/

  16. Neurovascular Compression After the Latarjet Procedure.

    PubMed

    Galvin, Joseph W; Romanowski, James R; Boykin, Robert E; Eichinger, Josef K; Lafosse, Laurent

    2015-12-01

    The Latarjet procedure is an established and effective option for the treatment of recurrent anterior shoulder instability. Symptomatic compression of the vasculature around the shoulder and adjacent brachial plexus is uncommon and may be difficult to diagnose and treat. The purpose of this report is to describe a patient with neurovascular compression of the axillary artery and brachial plexus after an open Latarjet procedure. This is the first known report of documented combined vascular and neurologic thoracic outlet syndrome after a Latarjet procedure. Evaluation of this suspected problem requires a detailed clinical examination and a dynamic angiogram to verify which neurovascular structures are compressed. Treatment includes decompression of the brachial plexus and axillary vasculature by releasing tethering scar tissue or the remaining pectoralis minor that is creating a constricting sling effect. An arthroscopic approach provides for a careful and specific decompression. Additionally, the authors provide a review of the literature for neurologic complications and management for these complications.

  17. Periprocedural management of anticoagulation in patients taking novel oral anticoagulants: Review of the literature and recommendations for specific populations and procedures.

    PubMed

    Mar, Philip L; Familtsev, Dmitry; Ezekowitz, Michael D; Lakkireddy, Dhanunjaya; Gopinathannair, Rakesh

    2016-01-01

    An increasing number of individuals are on novel oral anticoagulants (NOAC) for anticoagulation instead of vitamin K antagonists (VKA) and roughly 10% of these individuals will require interruption of these agents for procedures annually. Recent evidence surrounding bridging as well as the FDA approval of a new NOAC call for a comprehensive review and update regarding periprocedural NOAC management. The periprocedural management of NOACs involves striking a balance between the risks of bleeding and thromboembolism associated with interruption, bridging, and reinitiation of anticoagulation. NOACs have a distinct pharmacokinetic advantage in this setting with their quick onset and elimination from the body. Procedures at low risk for bleeding do not require interruption and can be scheduled at the start of the next dosing interval. Procedures at moderate-high risk of bleeding require interruption of NOAC for 5 half lives prior to the procedure to allow for adequate elimination of the drug. In light of new evidence highlighting the risks of bleeding, and given shorter "unprotected" times with NOAC interruption versus VKA, patients at low-moderate risk for thromboembolism should not be bridged when "unprotected" time is less than 96 h. For patients at high risk for thromboembolism, individual patient and surgical factors need to be considered before the decision to bridge is made. The benefit of bridging these patients who have a considerable risk of bleeding may not outweigh the benefits. Focused randomized studies on periprocedural management of NOACs are urgently needed.

  18. California School Lighting Design and Evaluation. A Procedure for the Prediction, Specification, and Evaluation of Visual Comfort and Visual Performance in Classrooms.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento.

    This guide is intended to help school administrators, members of school district governing boards, architects, and engineers objectively evaluate school lighting systems. The California school lighting design and evaluation procedure described provides a step-by-step design method that, when used properly, results in balanced lighting for school…

  19. Procedural knowledge

    NASA Technical Reports Server (NTRS)

    Georgeff, Michael P.; Lansky, Amy L.

    1986-01-01

    Much of commonsense knowledge about the real world is in the form of procedures or sequences of actions for achieving particular goals. In this paper, a formalism is presented for representing such knowledge using the notion of process. A declarative semantics for the representation is given, which allows a user to state facts about the effects of doing things in the problem domain of interest. An operational semantics is also provided, which shows how this knowledge can be used to achieve particular goals or to form intentions regarding their achievement. Given both semantics, the formalism additionally serves as an executable specification language suitable for constructing complex systems. A system based on this formalism is described, and examples involving control of an autonomous robot and fault diagnosis for NASA's Space Shuttle are provided.

  20. Justification of Drug Product Dissolution Rate and Drug Substance Particle Size Specifications Based on Absorption PBPK Modeling for Lesinurad Immediate Release Tablets.

    PubMed

    Pepin, Xavier J H; Flanagan, Talia R; Holt, David J; Eidelman, Anna; Treacy, Don; Rowlings, Colin E

    2016-09-06

    In silico absorption modeling has been performed, to assess the impact of in vitro dissolution on in vivo performance for ZURAMPIC (lesinurad) tablets. The dissolution profiles of lesinurad tablets generated using the quality control method were used as an input to a GastroPlus model to estimate in vivo dissolution in the various parts of the GI tract and predict human exposure. A model was set up, which accounts for differences of dosage form transit, dissolution, local pH in the GI tract, and fluid volumes available for dissolution. The predictive ability of the model was demonstrated by confirming that it can reproduce the Cmax observed for independent clinical trial. The model also indicated that drug product batches that pass the proposed dissolution specification of Q = 80% in 30 min are anticipated to be bioequivalent to the clinical reference batch. To further explore the dissolution space, additional simulations were performed using a theoretical dissolution profile below the proposed specification. The GastroPlus modeling indicates that such a batch will also be bioequivalent to standard clinical batches despite having a dissolution profile, which would fail the proposed dissolution specification of Q = 80% in 30 min. This demonstrates that the proposed dissolution specification sits comfortably within a region of dissolution performance where bioequivalence is anticipated and is not near an edge of failure for dissolution, providing additional confidence to the proposed specifications. Finally, simulations were performed using a virtual drug substance batch with a particle size distribution at the limit of the proposed specification for particle size. Based on these simulations, such a batch is also anticipated to be bioequivalent to clinical reference, demonstrating that the proposed specification limits for particle size distribution would give products bioequivalent to the pivotal clinical batches.

  1. Colocalization properties of elementary Ca(2+) release signals with structures specific to the contractile filaments and the tubular system of intact mouse skeletal muscle fibers.

    PubMed

    Georgiev, Tihomir; Zapiec, Bolek; Förderer, Moritz; Fink, Rainer H A; Vogel, Martin

    2015-12-01

    Ca(2+) regulates several important intracellular processes. We combined second harmonic generation (SHG) and two photon excited fluorescence microscopy (2PFM) to simultaneously record the SHG signal of the myosin filaments and localized elementary Ca(2+) release signals (LCSs). We found LCSs associated with Y-shaped structures of the myosin filament pattern (YMs), so called verniers, in intact mouse skeletal muscle fibers under hypertonic treatment. Ion channels crucial for the Ca(2+) regulation are located in the tubular system, a system that is important for Ca(2+) regulation and excitation-contraction coupling. We investigated the tubular system of intact, living mouse skeletal muscle fibers using 2PFM and the fluorescent Ca(2+) indicator Fluo-4 dissolved in the external solution or the membrane dye di-8-ANEPPS. We simultaneously measured the SHG signal from the myosin filaments of the skeletal muscle fibers. We found that at least a subset of the YMs observed in SHG images are closely juxtaposed with Y-shaped structures of the transverse tubules (YTs). The distances of corresponding YMs and YTs yield values between 1.3 μm and 4.1 μm including pixel uncertainty with a mean distance of 2.52±0.10 μm (S.E.M., n=41). Additionally, we observed that some of the linear-shaped areas in the tubular system are colocalized with linear-shaped areas in the SHG images. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Phenotypic variation in Aicardi-Goutières syndrome explained by cell-specific IFN-stimulated gene response and cytokine release.

    PubMed

    Cuadrado, Eloy; Michailidou, Iliana; van Bodegraven, Emma J; Jansen, Machiel H; Sluijs, Jacqueline A; Geerts, Dirk; Couraud, Pierre-Olivier; De Filippis, Lidia; Vescovi, Angelo L; Kuijpers, Taco W; Hol, Elly M

    2015-04-15

    Aicardi-Goutières syndrome (AGS) is a monogenic inflammatory encephalopathy caused by mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or MDA5. Mutations in those genes affect normal RNA/DNA intracellular metabolism and detection, triggering an autoimmune response with an increase in cerebral IFN-α production by astrocytes. Microangiopathy and vascular disease also contribute to the neuropathology in AGS. In this study, we report that AGS gene silencing of TREX1, SAMHD1, RNASEH2A, and ADAR1 by short hairpin RNAs in human neural stem cell-derived astrocytes, human primary astrocytes, and brain-derived endothelial cells leads to an antiviral status of these cells compared with nontarget short hairpin RNA-treated cells. We observed a distinct activation of the IFN-stimulated gene signature with a substantial increase in the release of proinflammatory cytokines (IL-6) and chemokines (CXCL10 and CCL5). A differential impact of AGS gene silencing was noted; silencing TREX1 gave rise to the most dramatic in both cell types. Our findings fit well with the observation that patients carrying mutations in TREX1 experience an earlier onset and fatal outcome. We provide in the present study, to our knowledge for the first time, insight into how astrocytic and endothelial activation of antiviral status may differentially lead to cerebral pathology, suggesting a rational link between proinflammatory mediators and disease severity in AGS. Copyright © 2015 by The American Association of Immunologists, Inc.

  3. Modification of the HCMV-specific IFN-γ release test (QuantiFERON-CMV) and a novel proposal for its application.

    PubMed

    Kobayashi, Takahiro; Sato, Jun-Ichi; Ikuta, Kazufumi; Kanno, Ryoko; Nishiyama, Kyoko; Koshizuka, Tetsuo; Ishioka, Ken; Suzutani, Tatsuo

    2017-08-09

    Human cytomegalovirus (HCMV) is universally distributed among humans without any adverse effects; however, it induces severe diseases in immunocompromised patients such as organ transplant recipients and AIDS patients. To manage these immunocompromised patients, an easy clinical examination for the monitoring of disease risk is required. In this study, we modified the interferon-γ (IFN-γ) release test (QuantiFERON(®)-CMV) using HCMV immediate early-1 (IE-1) or pp65 whole proteins, or UV-inactivated HCMV particles as an antigen. The response of heparinized peripheral blood from healthy volunteers to the pp65 protein showed an obvious dose-dependent sigmoid curve, although no correlation was observed between results of this assay and an ELISPOT assay. The addition of pp65 to the blood samples at a final concentration of 1×10(3) to 1×10(5) pg/ml was found to be optimum. Using this assay, we observed a significant enhancement in cellular immunity in volunteers after the daily ingestion of yogurt for 8 weeks, which suggested a novel application of the assay in addition to monitoring HCMV infection risk. IFN-γ secretion from peripheral blood cells on HCMV-antigen stimulation differed significantly between individuals; therefore, the assay could not be normalized. Nevertheless, it was found to be particularly useful for observing fluctuations in cellular immune activity on an individual level.

  4. A sequence-specific DNA binding small molecule triggers the release of immunogenic signals and phagocytosis in a model of B-cell lymphoma

    PubMed Central

    Kang, JeenJoo S.; Dervan, Peter B.

    2016-01-01

    Means to cause an immunogenic cell death could lead to significant insight into how cancer escapes immune control. In this study, we screened a library of five pyrrole–imidazole polyamides coding for different DNA sequences in a model of B-cell lymphoma for the upregulation of surface calreticulin, a pro-phagocytosis signal implicated in immunogenic cell death. We found that hairpin polyamide 1 triggers the release of the damage-associated molecular patterns calreticulin, ATP and HMGB1 in a slow necrotic-type cell death. Consistent with this signaling, we observed an increase in the rate of phagocytosis by macrophages after the cancer cells were exposed to polyamide 1. The DNA sequence preference of polyamide 1 is 5′-WGGGTW-3′ (where W = A/T), indicated by the pairing rules and confirmed by the Bind-n-Seq method. The close correspondence of this sequence with the telomere-repeat sequence suggests a potential mechanism of action through ligand binding at the telomere. This study reveals a chemical means to trigger an inflammatory necrotic cell death in cancer cells. PMID:26537405

  5. Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics.

    PubMed

    Rozov, A; Burnashev, N; Sakmann, B; Neher, E

    2001-03-15

    exogenously added BAPTA. However, BAPTA at concentrations > or = 1 mM also abolished facilitation. 5. Frequency-dependent depression of EPSPs in multipolar cells was not significantly reduced by EGTA. With BAPTA, the depression decreased at concentrations > 0.5 mM, concomitant with a reduction in amplitude of the first EPSP in a train. 6. An analysis is presented that interprets the effects of EGTA and BAPTA on synaptic efficacy and its short-term modification during paired-pulse stimulation in terms of changes in [Ca2+] at the release site ([Ca2+]RS) and that infers the affinity of the Ca2+ sensor from the dependence of unitary EPSPs on [Ca2+]o. 7. The results suggest that the target cell-specific difference in release from the terminals on bitufted or multipolar cells can be explained by a longer diffusional distance between Ca2+ channels and release sites and/or lower Ca2+ channels density in the terminals that contact bitufted cells. This would lead to a lower [Ca2+] at release sites and would also explain the higher apparent K(D) of the Ca2+ sensor in facilitating terminals.

  6. Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics

    PubMed Central

    Rozov, A; Burnashev, N; Sakmann, B; Neher, E

    2001-01-01

    also abolished facilitation. Frequency-dependent depression of EPSPs in multipolar cells was not significantly reduced by EGTA. With BAPTA, the depression decreased at concentrations > 0.5 mm, concomitant with a reduction in amplitude of the first EPSP in a train. An analysis is presented that interprets the effects of EGTA and BAPTA on synaptic efficacy and its short-term modification during paired-pulse stimulation in terms of changes in [Ca2+] at the release site ([Ca2+]RS) and that infers the affinity of the Ca2+ sensor from the dependence of unitary EPSPs on [Ca2+]o. The results suggest that the target cell-specific difference in release from the terminals on bitufted or multipolar cells can be explained by a longer diffusional distance between Ca2+ channels and release sites and/or lower Ca2+ channels density in the terminals that contact bitufted cells. This would lead to a lower [Ca2+] at release sites and would also explain the higher apparent KD of the Ca2+ sensor in facilitating terminals. PMID:11251060

  7. Time for considering constraints on procedural memory consolidation processes: Comment on Pan and Rickard (2015) with specific reference to developmental changes.

    PubMed

    Adi-Japha, Esther; Karni, Avi

    2016-05-01

    In the acquisition of some motor skills, sleep may be necessary for the completion of procedural memory consolidation processes, as expressed in delayed "offline" performance gains. Pan and Rickard (2015) conducted an original meta-analysis of the literature on performing an explicitly instructed finger movement sequence and tested the role of sleep versus wake in the enhancement of performance over posttraining delay periods. In this comment we propose that a more-biological, process-oriented framework is needed, allowing for more than a yes-no answer to the question addressed, and suggest methodological issues that may affect the target meta-analysis. We argue that different task demands, task conditions, and developmental differences should be considered a priori rather than expected to emerge from pooled data. For example, several recent studies have indicated that there is a qualitative change in the time course of procedural memory consolidation processes at puberty, between the ages of 12 and 17. Before puberty, consolidation processes are reflected in enhancement of task performance over sleep and wake periods alike. In their extensive set of relevant empirical data the authors included a number of developmental studies comparing children with adults (expecting "child status" effects) but did not fully consider developmental changes. We show that the inclusion of the 6 studies of childhood, comprising 13 groups, biases the meta-analysis toward the conclusion that skill enhancement is similar across wake and sleep periods. (PsycINFO Database Record

  8. [A specific feature of the procedure for determination of optical properties of turbid biological tissues and media in calculation tasks of medical noninvasive spectrophotometry].

    PubMed

    Rogatkin, D A

    2007-01-01

    The goal of this work is to discuss the problems of accuracy and reliability of the procedure for determination of optical per-unit-length properties of light-scattering biological tissues and media in medical noninvasive spectrophotometry. The determination procedure is based on the two-flux Kubelka-Munk approach. A simple one-dimensional model problem is formulated. The accurate solution of this problem is compared to its solution based on the Kubelka-Munk approach in various approximations. It is shown that in the general case of light-scattering and absorbing medium use of two independent transport coefficients (for scattering and absorption processes), as suggested in the conventional Kubelka-Munk approach, leads to errors of direct calculation of properties of backscattered and transmitted radiation in biological tissues. More valid and accurate expressions for transport coefficients can be obtained on the basis of a particular solution of the problem for a surface element of the model medium with known photometrical properties. This method makes it possible to determine accurately the radiation flux at the external boundary of the medium using the Kubelka-Munk approach. It is expected that solution of the inverse problem would make it possible to reconstruct accurately the optical properties of biological tissues from the experimental data.

  9. Syndactyly Release.

    PubMed

    Braun, Tara L; Trost, Jeffrey G; Pederson, William C

    2016-11-01

    Syndactyly is one of the most common congenital hand anomalies treated by pediatric plastic surgeons. Established principles of syndactyly separation dictate the timing and order of syndactyly release, with the goals of surgery being the creation of an anatomically normal webspace, tension-free closure of soft tissue, and return of function to the fingers. Numerous surgical methods have been described, many of which involve the use of local flaps to reconstruct the commissure and full-thickness skin grafts for coverage of raw areas. Recently, reconstructive techniques without the use of skin grafts have been devised, which work well for certain indications. Special considerations are described for complete, complex, and syndromic syndactylies. Outcomes for simple syndactyly release are typically good when surgical principles are followed, whereas complex syndactyly release tends to have less-favorable outcomes and more complications.

  10. Efficient tumor regression by adoptively transferred CEA-specific CAR-T cells associated with symptoms of mild cytokine release syndrome

    PubMed Central

    Wang, Linan; Ma, Ning; Okamoto, Sachiko; Amaishi, Yasunori; Sato, Eiichi; Seo, Naohiro; Mineno, Junichi; Takesako, Kazutoh; Kato, Takuma; Shiku, Hiroshi

    2016-01-01

    ABSTRACT Carcinoembryonic antigen (CEA) is a cell surface antigen highly expressed in various cancer cell types and in healthy tissues. It has the potential to be a target for chimeric antigen receptor (CAR)-modified T-cell therapy; however, the safety of this approach in terms of on-target/off-tumor effects needs to be determined. To address this issue in a clinically relevant model, we used a mouse model in which the T cells expressing CEA-specific CAR were transferred into tumor-bearing CEA-transgenic (Tg) mice that physiologically expressed CEA as a self-antigen. The adoptive transfer in conjunction with lymphodepleting and myeloablative preconditioning mediated significant tumor regression but caused weight loss in CEA-Tg, but not in wild-type mice. The weight loss was not associated with overt inflammation in the CEA-expressing gastrointestinal tract but was associated with malnutrition, reflected in elevated systemic levels of cytokines linked to anorexia, which could be controlled by the administration of an anti-IL-6 receptor monoclonal antibody without compromising efficacy. The apparent relationship between lymphodepleting and myeloablative preconditioning, efficacy, and off-tumor toxicity of CAR-T cells would necessitate the development of CEA-specific CAR-T cells with improved signaling domains that require less stringent preconditioning for their efficacy. Taken together, these results suggest that CEA-specific CAR-based adoptive T-cell therapy may be effective for patients with CEA+ solid tumors. Distinguishing the fine line between therapeutic efficacy and off-tumor toxicity would involve further modifications of CAR-T cells and preconditioning regimens. PMID:27757303

  11. Long-stored soil carbon released by prehistoric land use: Evidence from compound-specific radiocarbon analysis on Soppensee lake sediments

    NASA Astrophysics Data System (ADS)

    Gierga, Merle; Hajdas, Irka; van Raden, Ulrike J.; Gilli, Adrian; Wacker, Lukas; Sturm, Michael; Bernasconi, Stefano M.; Smittenberg, Rienk H.

    2016-07-01

    Compound-specific radiocarbon (14C) analyses allow studying the fate of individual biomarkers in ecosystems. In lakes with small catchments, terrestrial biomarkers have the potential to be used for the dating of sediments that lack the traditionally targeted terrestrial macrofossils, if the specific organic compounds are deposited soon after production. On the other hand, if the biomarkers have been stored for a significant amount of time in the soils of the catchment before transported to the lake, their age can be used to reconstruct changes in average residence time of organic material on land through time. Here we present a study based on compound-specific 14C analysis of the sedimentary record of Lake Soppensee, Switzerland, targeting long-chain n-alkanes of exclusive terrigenous origin, and comparing them with sediment ages obtained by high-resolution macrofossil dating. Additionally, we measured 14C ages of bulk organic matter and carbonate samples to assess the hard water effect. Prior to 3100 cal BP n-alkanes had about the same age as the sediment or they were slightly older, indicating that the vast majority of the terrestrial organic carbon transported to the lake had a short residence time on land. In the samples younger than 3100 cal BP an increasing offset is observed, indicating liberation of old buried soil organic matter that must have accumulated over the previous millennia. Our results indicate that as long as stable ecosystem conditions have prevailed, the distribution and isotopic composition of the n-alkanes can be used as environmental proxies in small catchments with limited surface runoff, confirming a few earlier studies.

  12. Efficient tumor regression by adoptively transferred CEA-specific CAR-T cells associated with symptoms of mild cytokine release syndrome.

    PubMed

    Wang, Linan; Ma, Ning; Okamoto, Sachiko; Amaishi, Yasunori; Sato, Eiichi; Seo, Naohiro; Mineno, Junichi; Takesako, Kazutoh; Kato, Takuma; Shiku, Hiroshi

    2016-01-01

    Carcinoembryonic antigen (CEA) is a cell surface antigen highly expressed in various cancer cell types and in healthy tissues. It has the potential to be a target for chimeric antigen receptor (CAR)-modified T-cell therapy; however, the safety of this approach in terms of on-target/off-tumor effects needs to be determined. To address this issue in a clinically relevant model, we used a mouse model in which the T cells expressing CEA-specific CAR were transferred into tumor-bearing CEA-transgenic (Tg) mice that physiologically expressed CEA as a self-antigen. The adoptive transfer in conjunction with lymphodepleting and myeloablative preconditioning mediated significant tumor regression but caused weight loss in CEA-Tg, but not in wild-type mice. The weight loss was not associated with overt inflammation in the CEA-expressing gastrointestinal tract but was associated with malnutrition, reflected in elevated systemic levels of cytokines linked to anorexia, which could be controlled by the administration of an anti-IL-6 receptor monoclonal antibody without compromising efficacy. The apparent relationship between lymphodepleting and myeloablative preconditioning, efficacy, and off-tumor toxicity of CAR-T cells would necessitate the development of CEA-specific CAR-T cells with improved signaling domains that require less stringent preconditioning for their efficacy. Taken together, these results suggest that CEA-specific CAR-based adoptive T-cell therapy may be effective for patients with CEA(+) solid tumors. Distinguishing the fine line between therapeutic efficacy and off-tumor toxicity would involve further modifications of CAR-T cells and preconditioning regimens.

  13. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis.

    PubMed

    Nam, Joon; Kim, Wooseong; Lee, Sunyoung; Jeong, Seongkeun; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

    2016-01-01

    Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.

  14. Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

    PubMed

    Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

    2015-09-01

    Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. (1R,2S,6R)-Papayanal: a new male-specific volatile compound released by the guava weevil Conotrachelus psidii (Coleoptera: Curculionidae).

    PubMed

    Romero-Frías, Alicia; Murata, Yasuhiro; Simões Bento, José Maurício; Osorio, Coralia

    2016-05-01

    The guava weevil, Conotrachelus psidii is an aggressive pest of guava (Psidium guajava L.) that causes irreparable damages inside the fruit. The volatile compounds of male and female insects were separately collected by headspace solid-phase microextraction or with dynamic headspace collection on a polymer sorbent, and comparatively analyzed by GC-MS. (1R,2S,6R)-2-Hydroxymethyl-2,6-dimethyl-3-oxabicyclo[4.2.0]octane (papayanol), and (1R,2S,6R)-2,6-dimethyl-3-oxabicyclo[4.2.0]octane-2-carbaldehyde (papayanal) were identified (ratio of 9:1, respectively) as male-specific guava weevil volatiles. Papayanal structure was confirmed by comparison of spectroscopic (EIMS) and chromatographic (retention time) data with those of the synthetic pure compound. The behavioral response of the above-mentioned compounds was studied in a Y-tube olfactometer bioassay, and their role as aggregation pheromone candidate components was suggested in this species.

  16. Expression of a Gonadotropin-Releasing Hormone Receptor-Simian Virus 40 T-Antigen Transgene Has Sex-Specific Effects on the Reproductive Axis

    PubMed Central

    Jeong, Kyeong-Hoon; Gill, John C.; Nosé, Vania; Parlow, Albert F.; Carroll, Rona S.; Kaiser, Ursula B.

    2009-01-01

    The GnRH receptor (GnRHR) responds to pulsatile GnRH signals to coordinate pituitary gonadotropin synthesis and secretion. Previously, a 1.2-kb fragment of the 5′-flanking region isolated from the mouse GnRHR gene was shown to target expression to pituitary gonadotropes in vivo. The 1.2-kb gene promoter fused to the simian virus 40 large T antigen (TAg) was used to generate transgenic mice that form gonadotrope-derived pituitary tumors at 4–5 months of age. Transgenic female mice have hypogonadotropic hypogonadism, infantile gonads, and are infertile throughout their life span, whereas males remain reproductively intact until their tumors become large. We hypothesized that the targeted TAg expression causes a sex-specific disruption of the reproductive axis at the level of the pituitary gland. To test this hypothesis, we characterized the pituitary gonadotropin β-subunit and TAg expression patterns, and measured plasma gonadotropin and gonadal steroid levels in female and male mice before and after pituitary tumor development. TAg expression was observed in transgenic females and males 15 d of age, before tumor development. Interestingly, and in contrast to the transgenic males, pituitary LHβ and FSHβ subunit protein levels, and plasma LH and FSH levels, were reduced in transgenic females. Reproductive organs in transgenic female mice remained underdeveloped but were normal in transgenic males. We conclude that the expression of the TAg transgene driven by the GnRHR gene promoter results in female-specific infertility due to disruption of gonadotropin production and secretion even before tumor development. PMID:19282386

  17. Toggle release

    NASA Technical Reports Server (NTRS)

    Graves, Thomas J. (Inventor); Yang, Robert A. (Inventor); Brown, Christopher W. (Inventor)

    1989-01-01

    A pyrotechnic actuated structural release device 10 which is mechanically two fault tolerant for release. The device 10 comprises a fastener plate 11 and fastener body 12, each attachable to a different one of a pair of structures to be joined. The fastener plate 11 and body 12 are fastenable by a toggle 13 supported at one end on the fastener plate and mounted for universal pivotal movement thereon. At its other end which is received in a central opening in the fastener body 12 and adapted for limited pivotal movement therein the toggle 13 is restrained by three retractable latching pins 61 symmetrically disposed in equiangular spacing about the axis of the toggle 13 and positionable in latching engagement with an end fitting on the toggle. Each pin 61 is individually retractable by combustion of a pyrotechnic charge 77, the expanding gases of which are applied to a pressure receiving face 67 on the latch pin 61 to effect its retraction from the toggle. While retraction of all three pins 62 releases the toggle, the fastener is mechanically two fault tolerant since the failure of any single one or pair of the latch pins to retract results in an asymmetrical loading on the toggle and its pivotal movement to effect a release. An annular bolt 18 is mounted on the fastener plate 11 as a support for the socket mounting 30, 37 of the toggle whereby its selective axial movement provides a means for preloading the toggle.

  18. Procedural pediatric dermatology.

    PubMed

    Metz, Brandie J

    2013-04-01

    Due to many factors, including parental anxiety, a child's inability to understand the necessity of a procedure and a child's unwillingness to cooperate, it can be much more challenging to perform dermatologic procedures in children. This article reviews pre-procedural preparation of patients and parents, techniques for minimizing injection-related pain and optimal timing of surgical intervention. The risks and benefits of general anesthesia in the setting of pediatric dermatologic procedures are discussed. Additionally, the surgical approach to a few specific types of birthmarks is addressed.

  19. Localization and phenotype-specific expression of ryanodine calcium release channels in C57BL6 and DBA/2J mouse strains

    PubMed Central

    Huang, Wei; Xing, Wei; Ryskamp, Daniel A.; Punzo, Claudio; Križaj, David

    2011-01-01

    The DBA/2J (D2) and C57BL6 (B6) mouse strains are widely used in research as models for anxiety, addiction and chronic glaucoma. D2, but not B6, animals develop elevated intraocular pressure (IOP) that leads to progressive degeneration of retinal ganglion cell (RGC) axons and perikarya. Here we compare the expression and localization of intracellular ryanodine receptor (RyR) Ca2+ store mechanisms in retinas from D2 and B6 animals. A subset of experiments included retinas from D2-Gpnmb+ mice as strain-specific controls for D2s. RT-PCR analysis showed 6–8 -fold upregulation RyR1, but not RyR2 or RyR3 transcripts, in D2 retinas. The upregulation was more pronounced in D2 retinas categorized as exhibiting moderate or severe glaucoma eyes compared to eyes with no/little glaucoma. In B6 retinas, RyR1 was expressed in neuronal perikarya/processes across all three retinal layers whereas little labeling was observed in astrocyte, microglial or Müller cell processes. In contrast, RyR1 antibodies strongly labeled radial processes of in D2 Müller glia, in which the staining colocalized with the activated glial stress marker GFAP. RyR1 staining in 1 month-old D2-Gpnmb+ strain resembled expression in B6 retinas whereas moderate RyR1, but not GFAP, localization to Müller glia was observed in 10–12 months - old D2-Gpnmb+ eyes. Both RyR1-ir and GFAP-ir were augmented in the microbead injection model of acute experimental glaucoma. We conclude that RyR1 exhibits differential expression and localization in two ubiquitously used mouse lines. While RyR1 signals can be regulated in a strain-specific manner, our data also suggest that RyR1 transcription is induced by early glial activation and/or elevation in intraocular pressure. PMID:21933672

  20. Localization and phenotype-specific expression of ryanodine calcium release channels in C57BL6 and DBA/2J mouse strains.

    PubMed

    Huang, Wei; Xing, Wei; Ryskamp, Daniel A; Punzo, Claudio; Križaj, David

    2011-11-01

    The DBA/2J (D2) and C57BL6 (B6) mouse strains are widely used in research as models for anxiety, addiction and chronic glaucoma. D2, but not B6, animals develop elevated intraocular pressure (IOP) that leads to progressive degeneration of retinal ganglion cell (RGC) axons and perikarya. Here we compare the expression and localization of intracellular ryanodine receptor (RyR) Ca(2+) store mechanisms in retinas from D2 and B6 animals. A subset of experiments included retinas from D2-Gpnmb(+) mice as strain-specific controls for D2s. RT-PCR analysis showed 6-8 -fold upregulation RyR1, but not RyR2 or RyR3 transcripts, in D2 retinas. The upregulation was more pronounced in D2 retinas categorized as exhibiting moderate or severe glaucoma eyes compared to eyes with no/little glaucoma. In B6 retinas, RyR1 was expressed in neuronal perikarya/processes across all three retinal layers whereas little labeling was observed in astrocyte, microglial or Müller cell processes. In contrast, RyR1 antibodies strongly labeled radial processes of in D2 Müller glia, in which the staining colocalized with the activated glial stress marker GFAP. RyR1 staining in 1 month-old D2-Gpnmb(+) strain resembled expression in B6 retinas whereas moderate RyR1, but not GFAP, localization to Müller glia was observed in 10-12 months - old D2-Gpnmb(+) eyes. Both RyR1-ir and GFAP-ir were augmented in the microbead injection model of acute experimental glaucoma. We conclude that RyR1 exhibits differential expression and localization in two ubiquitously used mouse lines. While RyR1 signals can be regulated in a strain-specific manner, our data also suggest that RyR1 transcription is induced by early glial activation and/or elevation in intraocular pressure. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Artemin, a diapause-specific chaperone, contributes to the stress tolerance of Artemia franciscana cysts and influences their release from females.

    PubMed

    King, Allison M; Toxopeus, Jantina; MacRae, Thomas H

    2014-05-15

    Females of the crustacean Artemia franciscana produce either motile nauplii or gastrula stage embryos enclosed in a shell impermeable to nonvolatile compounds and known as cysts. The encysted embryos enter diapause, a state of greatly reduced metabolism and profound stress tolerance. Artemin, a diapause-specific ferritin homolog in cysts has molecular chaperone activity in vitro. Artemin represents 7.2% of soluble protein in cysts, approximately equal to the amount of p26, a small heat shock protein. However, there is almost twice as much artemin mRNA in cysts as compared with p26 mRNA, suggesting that artemin mRNA is translated less efficiently. RNA interference employing the injection of artemin double-stranded RNA into the egg sacs of A. franciscana females substantially reduced artemin mRNA and protein in cysts. Decreasing artemin diminished desiccation and freezing tolerance of cysts, demonstrating a role for this protein in stress resistance. Knockdown of artemin increased the time required for complete discharge of a brood of cysts carried within a female from a few hours up to 4 days, an effect weakened in successive broods. Artemin, an abundant molecular chaperone, contributes to stress tolerance of A. franciscana cysts while influencing their development and/or exit from females. © 2014. Published by The Company of Biologists Ltd.

  2. Detection of fuel release in a nuclear accident: a method for preconcentration and isolation of reactor-borne (239)Np using ion-specific extraction chromatography.

    PubMed

    Rosenberg, Brett L; Shozugawa, Katsumi; Steinhauser, Georg

    2015-09-01

    Although actinides are the most informative elements with respect to the nature of a nuclear accident, plutonium analysis is complicated by the background created by fallout from atmospheric nuclear explosions. Therefore, we propose (239)Np, a short-lived actinide that emits several γ rays, as a preferred proxy. The aim of this study was to screen ion specific extraction chromatography resins (RE-, TEVA-, UTEVA-, TRU-, and Actinide-Resin) for the highest possible recovery and separation of trace amounts of (239)Np from samples with large activities of fission products such as radiocesium, radioiodine, and, most importantly, radiotellurium, the latter of which causes spectral interference in gamma spectrometry through overlapping peaks with (239)Np. The investigated environmental media for these separations were aqueous solutions simulating rainwater and soil. Spiked samples containing (239)Np and the aforementioned volatile radionuclides were separated through extraction chromatographic columns to ascertain the most effective means of separating (239)Np from other fission products for detection by gamma spectroscopy. We propose a method for nuclear accident preparedness based on the use of Eichrom's RE-Resin. The proposed method was found most effective for isolating (239)Np from interfering radionuclides in both aqueous solution and soil using 8 M HNO3 as the loading solution and H2O as the eluent. The RE-Resin outperforms the more commonly used TEVA-Resin because the TEVA-Resin showed a higher affinity for interfering radiotellurium and radioiodine.

  3. Prodrugs of peptides. 6. Bioreversible derivatives of thyrotropin-releasing hormone (TRH) with increased lipophilicity and resistance to cleavage by the TRH-specific serum enzyme.

    PubMed

    Bundgaard, H; Møss, J

    1990-09-01

    Bioreversible derivatization of TRH (pGlu-His-Pro-NH2) to protect the tripeptide against rapid enzymatic inactivation in the systemic circulation and to improve the lipophilicity of this highly hydrophilic peptide was performed by N-acylation of the imidazole group of the histidine residue with various chloroformates. Whereas TRH was rapidly hydrolyzed at its pGlu-His bond in human plasma by a TRH-specific pyroglutamyl aminopeptidase serum enzyme, the N-alkoxycarbonyl derivatives were resistant to cleavage by the enzyme. On the other hand, these derivatives are readily bioreversible as the parent TRH is formed quantitatively from the derivatives by spontaneous hydrolysis or by plasma esterase-catalyzed hydrolysis. In addition to protecting the parent TRH against rapid inactivation in the circulation and hence potentially prolonging the duration of action of TRH in vivo, the N-alkoxycarbonyl prodrug derivatives were much more lipophilic than TRH as assessed by octanol-buffer partitioning. This property may enhance prodrug penetration of the blood-brain barrier and various other biomembranes compared to the parent peptide.

  4. Optogenetic control of ATP release

    NASA Astrophysics Data System (ADS)

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

    2013-03-01

    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  5. Need for Two-Year Patient-Reported Outcomes Score for Lumbar Spine Surgery Is Procedure-Specific: Analysis From a Prospective Longitudinal Spine Registry.

    PubMed

    Kim, Elliott J; Chotai, Silky; Archer, Kristin R; Bydon, Mohamad; Asher, Anthony L; Devin, Clinton J

    2017-09-01

    Retrospective analysis of prospectively collected data. The aim of this study was to determine whether 1-year patient-reported outcomes (PROs) can accurately assess effective care for patients undergoing surgery for degenerative lumbar spine disease. Prospective longitudinal PROs registries provide a means to accurately assess outcomes and determine the relative effectiveness of various spine treatments. Obtaining long-term PROs can be costly and challenging. Patients enrolled into a prospective registry who underwent lumbar spine surgery for degenerative disease were included. Baseline, 1-year, and 2-year Oswestry Disability Index (ODI) scores were captured. Previously published minimum clinically important difference (MCID) for ODI (14.9) was used. Multivariable linear regression model was created to derive model-estimated 2-year ODI scores. Absolute differences between 1-year and 2-year ODI were compared to absolute differences between 2-year and model-estimated 2-year ODI. Concordance rates in achieving MCID at 1-year and 2-year and predictive values were calculated. A total of 868 patients were analyzed. One-year ODI scores differed from 2-year scores by an absolute difference of 9.7 ± 8.9 points and predictive model-estimated 2-year scores differed from actual 2-year scores by 8.8 ± 7.3 points. The model-estimated 2-year ODI was significantly different than actual 1-year ODI in assessing actual 2-year ODI for all procedures (P = 0.001) except for primary (P = 0.932) and revision microdiscectomy (P = 0.978) and primary laminectomy (P = 0.267). The discordance rates of achieving or not achieving MCID for ODI ranged from 8% to 27%. Concordance rate was about 90% for primary and revision microdiscectomy. The positive and negative predictive value of 1-year ODI to predict 2-year ODI was 83% and 67% for all procedures and 92% and 67% for primary and 100% and 86% for revision microdiscectomy respectively. One-year disability outcomes can

  6. Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17.

    PubMed

    Rehfeld, Jens F; Zhu, Xiaorong; Norrbom, Christina; Bundgaard, Jens R; Johnsen, Anders H; Nielsen, John E; Vikesaa, Jonas; Stein, Jeffrey; Dey, Arunangsu; Steiner, Donald F; Friis-Hansen, Lennart

    2008-10-01

    Cellular synthesis of peptide hormones requires PCs (prohormone convertases) for the endoproteolysis of prohormones. Antral G-cells synthesize the most gastrin and express PC1/3, 2 and 5/6 in the rat and human. But the cleavage sites in progastrin for each PC have not been determined. Therefore, in the present study, we measured the concentrations of progastrin, processing intermediates and alpha-amidated gastrins in antral extracts from PC1/3-null mice and compared the results with those in mice lacking PC2 and wild-type controls. The expression of PCs was examined by immunocytochemistry and in situ hybridization of mouse G-cells. Finally, the in vitro effect of recombinant PC5/6 on progastrin and progastrin fragments containing the relevant dibasic cleavage sites was also examined. The results showed that mouse G-cells express PC1/3, 2 and 5/6. The concentration of progastrin in PC1/3-null mice was elevated 3-fold. Chromatography showed that cleavage of the Arg(36)Arg(37) and Arg(73)Arg(74) sites were grossly decreased. Accordingly, the concentrations of progastrin products were markedly reduced, alpha-amidated gastrins (-34 and -17) being 25% of normal. Lack of PC1/3 was without effect on the third dibasic site (Lys(53)Lys(54)), which is the only processing site for PC2. Recombinant PC5/6 did not cleave any of the dibasic processing sites in progastrin and fragments containing the relevant dibasic processing sites. The complementary cleavages of PC1/3 and 2, however, suffice to explain most of the normal endoproteolysis of progastrin. Moreover, the results show that PCs react differently to the same dibasic sequences, suggesting that additional structural factors modulate the substrate specificity.

  7. Controlled Release Applications of Organometals.

    ERIC Educational Resources Information Center

    Thayer, John S.

    1981-01-01

    Reviews two classes of controlled release organometals: (1) distributional, to distribute bioactive materials to control a certain target organism; and (2) protective, to protect surface or interior of some structure from attach by organisms. Specific examples are given including a discussion of controlled release for schistosomiasis. (SK)

  8. Controlled Release Applications of Organometals.

    ERIC Educational Resources Information Center

    Thayer, John S.

    1981-01-01

    Reviews two classes of controlled release organometals: (1) distributional, to distribute bioactive materials to control a certain target organism; and (2) protective, to protect surface or interior of some structure from attach by organisms. Specific examples are given including a discussion of controlled release for schistosomiasis. (SK)

  9. Statistical correlation of the soil incubation and the accelerated laboratory extraction methods to estimate nitrogen release rates of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry; Obreza, Thomas; Leary, Emily; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release patterns of enhanced-efficiency fertilizers (EEFs) during the last few decades. These technologies have been developed mainly by manufacturers and are product-specific based on the regulation and analysis of each EEF product. Despite previous efforts to characterize nutrient release of slow-release fertilizer (SRF) and controlled-release fertilizer (CRF) materials, no official method exists to assess their nutrient release patterns. However, the increased production and distribution of EEFs in specialty and nonspecialty markets requires an appropriate method to verify nutrient claims and material performance. Nonlinear regression was used to establish a correlation between the data generated from a 180-day soil incubation-column leaching procedure and 74 h accelerated lab extraction method, and to develop a model that can predict the 180-day nitrogen (N) release curve for a specific SRF and CRF product based on the data from the accelerated laboratory extraction method. Based on the R2 > 0.90 obtained for most materials, results indicated that the data generated from the 74 h accelerated lab extraction method could be used to predict N release from the selected materials during 180 days, including those fertilizers that require biological activity for N release.

  10. Patient-reported opioid analgesic requirements after elective inguinal hernia repair: A call for procedure-specific opioid-administration strategies.

    PubMed

    Mylonas, Konstantinos S; Reinhorn, Michael; Ott, Lauren R; Westfal, Maggie L; Masiakos, Peter T

    2017-08-01

    A better understanding of the analgesia needs of patients who undergo common operative procedures is necessary as we address the growing opioid public health crisis in the United States. The aim of this study was to evaluate patient experience with our opioid prescribing practice after elective inguinal hernia repairs. A prospective, observational study was conducted between October 1, 2015, and September 30, 2016, in a single-surgeon, high-volume, practice of inguinal hernia operation. Adult patients undergoing elective inguinal herniorrhaphy under local anesthesia with intravenous sedation were invited to participate. All patients were prescribed 10 opioid analgesic tablets postoperatively and were counseled to reserve opioids for pain not controlled by nonopioid analgesics. Their experience was captured by completing a questionnaire 2 to 3 weeks postoperatively during their postoperative visit. A total of 185 patients were surveyed. The majority of the participants were males (177, 95.7%) and ≥60 years old (96, 51.9%). Of the 185 patients, 159 (85.9%) reported using ≤4 opioid tablets; 110 patients (59.5%) reported that they used no opioid analgesics postoperatively. None of the patients was taking opioids within 7 days of their postoperative appointment. Of the 147 patients who were employed, 111 (75.5%) reported missing ≤3 work days, 57 of whom (51.4%) missed no work at all. Patients who were employed were more likely to take opioid analgesics postoperatively (P = .049). Patients who took no opioid analgesics experienced less maximum (P < .001) and persistent groin pain (P = .037). Pain interfered less with daily activities (P = .012) and leisure activities (P = .018) for patients who did not use opioids. The majority of our patients reported that they did not require any opioid analgesics, and nearly all of those who thought that they did need opioids used <5 tablets. Our data suggest that for elective inguinal hernia repair under a local

  11. Specific interactions between diphenhydramine and alpha-helical poly(glutamic acid)--a new ion-pairing complex for taste masking and pH-controlled diphenhydramine release.

    PubMed

    Agresti, Ciara; Tu, Zhigang; Ng, Charlene; Yang, Yongsheng; Liang, Jun F

    2008-09-01

    Formation of drug/excipient complex through ionic interactions has proven to be very effective for both controlled release and taste masking. Unfortunately, the ionic interactions between drugs and small molecule excipients are usually weak, and the stability of the formed complexes can be greatly influenced by solution ionic strength. In this study, we explored to formulate diphenhydramine (DPH), a very bitter tasting drug, using small molecular weight and carboxyl group containing polymers. Studies showed that DPH interacted with alpha-helical poly(glutamic acid) specifically to produce DPH/poly(glutamic acid) complexes, mostly spherical in shape with a diameter of around 1.0 microm. Other drugs with similar chemical structures as DPH, such as phenylephrine and pseudoephedrine, could not form complexes with poly(glutamic acid) or other polymers under the same conditions. Although DPH in DPH/poly(glutamic acid) complexes existed amorphously, it showed increased stability. In vitro studies using electronic tongue demonstrated that poly(glutamic acid) might be as effective as sucralose for DPH bitter taste blocking. In addition, DPH/poly(glutamic acid) complexes were not stable in neutral or weak acidic (pH>5) environments and dissolved rapidly and completely. Therefore, DPH/poly(glutamic acid) complex may serve as a new formulation for taste masking and controlled DPH release in gastrointestinal tract. This is the first report that small molecule drugs can interact with peptides of specific secondary structures to form stable complexes. In addition to greatly expanded ion-pairing excipient pool, application of peptides in drug formulation may also solve the selectivity and stability problems faced by current small molecule excipients.

  12. Ca2+ release from the endoplasmic reticulum of NY-ESO-1 specific T cells is modulated by the affinity of T cell receptor and by the use of the CD8 co-receptor

    PubMed Central

    Stewart-Jones, Guillaume; Shepherd, Dawn; Bossi, Giovanna; Wooldridge, Linda; Hutchinson, Sarah L.; Sewell, Andrew K.; Griffiths, Gillian M.; van der Merwe, P. Anton; Jones, E. Yvonne; Galione, Antony; Cerundolo, Vincenzo

    2014-01-01

    Although several cancer immunotherapy strategies are currently based on the use of analog peptides and on the modulation of the TCR affinity of adoptively transferred T cells, it remains unclear whether tumor specific T cell activation by strong and weak TCR stimuli evoke different Ca2+ signatures from the Ca2+ intracellular stores and whether the amplitude of Ca2+ release from the ER can be further modulated by co-receptor binding to peptide/MHC complexes (pMHC). We here combined functional, structural and kinetic measurements to correlate the intensity of Ca2+ signals triggered by the stimulation of the 1G4 T cell clone specific to the tumor epitope NY-ESO-1157–165. Two analogs of the NY-ESO-1157–165 peptide, having similar affinity to HLA-A2 molecules, but a six-fold difference in binding affinity for the 1G4 TCR, resulted in different Ca2+ signals and T cell activation. 1G4 stimulation by the stronger stimulus emptied the ER of stored Ca2+, even in the absence of CD8 binding, resulting in sustained Ca2+ influx. In contrast, the weaker stimulus induced only partial emptying of stored Ca2+, resulting in significantly diminished and oscillatory Ca2+ signals, which was enhanced by CD8 binding. Our data define the range of TCR/pMHC affinities required to induce depletion of Ca2+ from intracellular stores and provide insights into the ability of T cells to tailor the use of the CD8 co-receptor to enhance Ca2+ release from the ER. This in turn modulates Ca2+ influx from the extracellular environment, ultimately controlling T cell activation. PMID:20053942

  13. Release of organic chelating agents from solidified decontamination wastes

    SciTech Connect

    Piciulo, P.L.; Adams, J.W.; Milian, L.W.

    1986-01-01

    In order to provide technical information needed by the US Nuclear Regulatory Commission to evaluate the adequacy of near-surface disposal of decontamination wastes, Brookhaven National Laboratory has measured the release of organic complexing agents from simulated decontamination resin wastes solidified in cement and vinyl ester-styrene. The simulated waste consisted of either mixed bed ion-exchange resins or anion exchange resins equilibrated with EDTA, oxalic acid, citric acid, picolinic acid, formic acid, simulated LOMI reagent or the LND-101A decontamination reagent. The standard procedure ANS 16.1 appeared to be adequate for determining a leachability index for organic acids for comparing the leach resistance of decontamination waste forms. Leachability indexes appeared to be specific for each organic acid. Further, the apparent diffusivities were generally less than those observed for Cs releases from cement wastes forms. The finder material and the composition of the simulated wastes affected the release of the reagents.

  14. Inexpensive, rapid procedure for bulk purification of cellulase-free beta-1,4-D-xylanase of high specific activity.

    PubMed

    Tan, L U; Yu, E K; Louis-Seize, G W; Saddler, J N

    1987-07-01

    A process has been developed for the bulk purification of cellulase-free beta-1,4-D-xylanase from the fungus Trichoderma harzianum E58. The process involved the primary step of ultrafiltering the culture filtrate via a 10,000-molecular-weight cut-off membrane to separate the cellulase (retentate) and xylanase (permeate) fractions. The cellulase component was concentrated by 40- to 60-fold, resulting in an enzyme complex that could effectively hydrolyze high concentrations of cellulose and xylan to glucose and xylose. The xylanase was concentrated and solvent exchanged by adsorption to a cationic exchanger, SP-ZetaPrep 250, followed by elution with a pH change in the buffer to give a purified and concentrated xylanase complex dissolved in a low-salt buffer. The resultant xylanase system was pure by the criteria of sodium dodecyl sulfate polyacrylamide electrophoresis, had a very high specific activity of 2400 IU/mg protein, was virtually free of filter paper activity, and had a ratio of contaminating filter paper activity of 2 x 10(-6) (0.009% endoglucanase activity). Approximately 3.3 g protein, which contained in excess of 7 x 10(6) IU xylanase activity, was obtained from 17 L original culture filtrate. The process scheme was designed to facilitate scale-up to an industrial level of production.

  15. Inexpensive, rapid procedure for bulk purification of cellulase-free. beta. -1,4-D-xylanase of high specific activity

    SciTech Connect

    Tan, L.U.L.; Yu, E.K.C.; Louis-Seize, G.W.; Saddler, J.N.

    1987-01-01

    A process has been developed for the bulk purification of cellulase-free ..beta..-14-D-xylanase from the fungus Tirchoderma harzianum E58. The process involved the primary step of ultrafiltering the culture filtrate via a 10,000-molecular-weight cut-off membrane to separate the cellulase (retentate) and xylanase (permeate) fractions. The cellulase component was concentrated by 40- to 60-fold, resulting in an enzyme complex that could effectively hydrolyze high concentrations of cellulose and xylan to glucose and xylose. The xylanase was concentrated and solvent exchanged by adsorption to a cationic exchanger, SP-ZetaPrep 250, followed by elution with a pH change in the buffer to give a purified and concentrated xylanase complex dissolved in a low-salt buffer. The resultant xylanase system was pure by the criteria of sodium dodecyl sulfate polyacrylamide electrophoresis, had a very high specific activity of 2400 IU/mg protein, was virtually free of filter paper activity, and had a ratio of contaminating filter paper activity of 2 x 10/sup -6/. Approximately 3.3 g protein, which contained in excess of 7 x 10/sup 6/ IU xylanase activity was obtained from 17 L original culture filtrate. The process scheme was designed to facilitate scale-up to an industrial level of production.

  16. TMACS Test Procedure TP007: System administration

    SciTech Connect

    Scanlan, P.; Washburn, S.; Seghers, R.

    1994-05-24

    The TMACS Software Project Test Procedures translate the project`s acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure tests the TMACS System Administration functions.

  17. TMACS Test Procedure TP002: Trending

    SciTech Connect

    Scanlan, P.K.

    1994-08-29

    The TMACS Software Project Test Procedures translate the project`s acceptance criteria into test steps. Software releases are certified when the affected Test Procedures are successfully performed and the customers authorize installation of these changes. This Test Procedure tests the TMACS Trending functions.

  18. Common procedures in rabbits.

    PubMed

    Graham, Jennifer

    2006-05-01

    Rabbits are popular companion animals that present to veterinary clinics for routine and emergency care. Clinics equipped for treat-ing dogs and cats may be easily adapted to accommodate rabbits. This article reviews common procedures performed by the clinician specific to rabbits. Topics include handling and restraint, triage and patient assessment, sample collection, and supportive care techniques. Miscellaneous procedures, including anesthetic delivery, nasolacrimal duct flushing, and ear cleaning, are also discussed.

  19. 28 CFR 571.13 - Institution release preparation program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... nutrition. (2) Employment. (3) Personal finance/consumer skills. (4) Information/community resources. (5) Release requirements and procedures. (6) Personal growth and development. (c) To assist in the release...

  20. 28 CFR 571.13 - Institution release preparation program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... nutrition. (2) Employment. (3) Personal finance/consumer skills. (4) Information/community resources. (5) Release requirements and procedures. (6) Personal growth and development. (c) To assist in the release...

  1. 28 CFR 571.13 - Institution release preparation program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... curriculum of topics/courses organized into six broad categories. The six categories are: (1) Health and...) Release requirements and procedures. (6) Personal growth and development. (c) To assist in the release...

  2. 28 CFR 571.13 - Institution release preparation program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... curriculum of topics/courses organized into six broad categories. The six categories are: (1) Health and...) Release requirements and procedures. (6) Personal growth and development. (c) To assist in the release...

  3. “Kinin danger signals proteolytically released by gingipain induce fimbriae-specific IFN-γ and IL-17-producing T cells in mice infected intramucosally with Porphyromonas gingivalis”

    PubMed Central

    Monteiro, Ana Carolina; Scovino, Aline; Raposo, Susane; Gaze, Vinicius Mussa; Cruz, Catia; Svensjö, Erik; Narciso, Marcelo Sampaio; Colombo, Ana Paula; Pesquero, João B.; Feres-Filho, Eduardo; Nguyen, Ky-Anh; Sroka, Aneta; Potempa, Jan; Scharfstein, Julio

    2009-01-01

    Porphyromonas gingivalis, a gram-negative bacterium that causes periodontitis, activates the kinin system via the cysteine protease R-gingipain. Using a model of buccal infection based on P. gingivalis inoculation in the anterior mandibular vestibule, here we studied whether kinins released by gingipain may link mucosal inflammation to T cell-dependent immunity through the activation of bradykinin B2 receptors (B2R). Our data show that P. gingivalis W83 (WT), but not gingipain deficient mutant or WT bacteria pretreated with gingipain inhibitors, elicited buccal edema and gingivitis in Balb/C or C57BL/6 mice. Studies in TLR2−/−, B2R−/− and neutrophil-depleted C57Bl/6 mice revealed that P. gingivalis induced edema through the sequential activation of TLR2/neutrophils, with the initial plasma leakage being amplified by gingipain-dependent release of vasoactive kinins from plasma-borne kininogens. We then used fimbriae (Fim) Ag as a read-out to verify if activation of the TLR2>PMN>B2R axis at early-stages of mucosal infection had impact on adaptive immunity. Analyzes of T cell recall responses indicated that gingipain drives B2R-dependent generation of IFN-γ-producing Fim T cells in submandibular draining LNs of Balb/C and C57BL/6 mice while IL-17-producing Fim T cells were generated only in Balb/C mice. In summary, our studies suggest that two virulence factors, LPS (an atypical TLR2 ligand) and gingipain, forges a trans-cellular cross-talk between TLR2/B2R, thus forming an innate axis that guides the development of Fim-specific T cells in mice challenged intrabuccally by P. gingivalis. Ongoing research may clarify if kinin-driven modulation of T cell responses may also influence the severity of chronic periodontitis. PMID:19687097

  4. Dental Procedures.

    PubMed

    Ramponi, Denise R

    2016-01-01

    Dental problems are a common complaint in emergency departments in the United States. There are a wide variety of dental issues addressed in emergency department visits such as dental caries, loose teeth, dental trauma, gingival infections, and dry socket syndrome. Review of the most common dental blocks and dental procedures will allow the practitioner the opportunity to make the patient more comfortable and reduce the amount of analgesia the patient will need upon discharge. Familiarity with the dental equipment, tooth, and mouth anatomy will help prepare the practitioner for to perform these dental procedures.

  5. 45 CFR 35.8 - Release.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Release. 35.8 Section 35.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION TORT CLAIMS AGAINST THE GOVERNMENT Procedures § 35.8 Release. Acceptance by the claimant, his agent or legal representative, of any award, compromise...

  6. 34 CFR 35.8 - Release.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Release. 35.8 Section 35.8 Education Office of the Secretary, Department of Education TORT CLAIMS AGAINST THE GOVERNMENT Procedures § 35.8 Release. Acceptance by the claimant, his agent or legal representative, of any award, compromise or settlement made...

  7. 40 CFR 302.8 - Continuous releases.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... release data, engineering estimates, knowledge of operating procedures, or best professional judgment to...) The environmental medium(a) affected by the release: (1) If surface water, the name of the surface... use; (3) If a lake, the surface area (in acres) and average depth (in feet or meters); (4) If on or...

  8. 7 CFR 356.5 - Bonded release.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Bonded release. 356.5 Section 356.5 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FORFEITURE PROCEDURES § 356.5 Bonded release. (a) The Deputy Administrator...

  9. Site-specific PEGylation for high-yield preparation of Lys(21)-amine PEGylated growth hormone-releasing factor (GRF) (1-29) using a GRF(1-29) derivative FMOC-protected at Tyr(1) and Lys(12).

    PubMed

    Youn, Yu Seok; Lee, Kang Choon

    2007-01-01

    PEGylation has been viewed as an effective means of overcoming the therapeutic restriction of growth hormone-releasing factor (1-29) (GRF(1-29)) due to its short biological lifetime caused by severe proteolysis and rapid glomerular filtration. Of three isomers according to the PEGylation sites (Tyr1, Lys12, or Lys21), PEGylated GRF(1-29) at Lys21-amine (Lys21-PEG-GRF(1-29)) was shown to have the highest bioactivity. In this report, we propose a unique two-step site-specific PEGylation method capable of producing only Lys21-PEG-GRF(1-29) with a single composition in high yield using a GRF(1-29) derivative protected at Tyr1 and Lys12 and remained available at Lys21 (FMOC1,12-GRF(1-29)). The first step of this reaction involved the PEG attachment to FMOC1,12-GRF(1-29), and the second step involved the removal of FMOC moieties. This PEGylation process was optimized at the following conditions: 0.2-0.3% (v/v) triethylamine concentration, 5.0-6.0-fold molar amount of PEG, reaction temperature of 25-45 degrees C, and reaction time of 30 min. Under these conditions, the maximum yield of Lys21-PEG-GRF(1-29) produced was ca. approximately 95%, 6.3-fold higher than that by nonspecific PEGylation at pH 8.5. Significantly, this site-specific Lys21-PEG-GRF(1-29) was found to have greatly increased resistance to rat plasma, liver, and kidney homogenates, with 7.0-, 25.4-, and 16.4-fold longer half-lives vs GRF(1-29), respectively. Furthermore, 125I-Lys21-PEG-GRF(1-29) displayed significantly reduced liver and kidney distributions and extended blood presence vs 125I-GRF(1-29) in rats. Due to these benefits, Lys21-PEG-GRF(1-29) displayed an enhanced initial growth hormone release in vivo despite having 15% remaining activity in vitro. This devised PEGylation method using an FMOC-protection/deprotection strategy would provide great usefulness for PEGylating bioactive peptides in terms of improved biological potency, elevated production yield, and a uniform composition.

  10. Grievance Procedures.

    ERIC Educational Resources Information Center

    Eisenhower, R. Warren

    Because grievances are unavoidable, it is essential for organizations, such as the schools, to utilize an efficient, effective procedure to handle friction between employers and employees. Through successive steps, representatives of labor and management attempt to resolve the grievance, first with meetings of lower level representatives (such as…

  11. Specific Learning Outcomes Attributable to Study Procedures.

    ERIC Educational Resources Information Center

    Shanahan, Timothy

    The amount and structure of prose learning derived from vocabulary definition and graphic post-organizer construction methods of independent study tasks is examined. Undergraduate subjects (n=144) read a 2000-word passage in a 20-minute reading period. Two subject groups performed text information tasks while a third acted as a control to measure…

  12. New procedure of quantitative mapping of Ti and Al released from dental implant and Mg, Ca, Fe, Zn, Cu, Mn as physiological elements in oral mucosa by LA-ICP-MS.

    PubMed

    Sajnóg, Adam; Hanć, Anetta; Koczorowski, Ryszard; Barałkiewicz, Danuta

    2017-12-01

    A new procedure for determination of elements derived from titanium implants and physiological elements in soft tissues by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is presented. The analytical procedure was developed which involved preparation of in-house matrix matched solid standards with analyte addition based on certified reference material (CRM) MODAS-4 Cormorant Tissue. Addition of gelatin, serving as a binding agent, essentially improved physical properties of standards. Performance of the analytical method was assayed and validated by calculating parameters like precision, detection limits, trueness and recovery of analyte addition using additional CRM - ERM-BB184 Bovine Muscle. Analyte addition was additionally confirmed by microwave digestion of solid standards and analysis by solution nebulization ICP-MS. The detection limits are in range 1.8μgg(-1) to 450μgg(-1) for Mn and Ca respectively. The precision values range from 7.3% to 42% for Al and Zn respectively. The estimated recoveries of analyte addition line within scope of 83%-153% for Mn and Cu respectively. Oral mucosa samples taken from patients treated with titanium dental implants were examined using developed analytical method. Standards and tissue samples were cryocut into 30µm thin sections. LA-ICP-MS allowed to obtain two-dimensional maps of distribution of elements in tested samples which revealed high content of Ti and Al derived from implants. Photographs from optical microscope displayed numerous particles with µm size in oral mucosa samples which suggests that they are residues from implantation procedure. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Individualized optimal release angles in discus throwing.

    PubMed

    Leigh, Steve; Liu, Hui; Hubbard, Mont; Yu, Bing

    2010-02-10

    The purpose of this study was to determine individualized optimal release angles for elite discus throwers. Three-dimensional coordinate data were obtained for at least 10 competitive trials for each subject. Regression relationships between release speed and release angle, and between aerodynamic distance and release angle were determined for each subject. These relationships were linear with subject-specific characteristics. The subject-specific relationships between release speed and release angle may be due to subjects' technical and physical characteristics. The subject-specific relationships between aerodynamic distance and release angle may be due to interactions between the release angle, the angle of attack, and the aerodynamic distance. Optimal release angles were estimated for each subject using the regression relationships and equations of projectile motion. The estimated optimal release angle was different for different subjects, and ranged from 35 degrees to 44 degrees . The results of this study demonstrate that the optimal release angle for discus throwing is thrower-specific. The release angles used by elite discus throwers in competition are not necessarily optimal for all discus throwers, or even themselves. The results of this study provide significant information for understanding the biomechanics of discus throwing techniques.

  14. A procedure for culturing astrocytes from white matter and the application of the siRNA technique for silencing the expression of their specific marker, S100A4.

    PubMed

    Kozlova, Elena N; Takenaga, Keizo

    2005-07-01

    White matter astrocytes have physiological functions which are distinct from those of astrocytes in gray matter. White matter becomes highly non-permissive to neurite growth after injury, but the role of white matter astrocytes in this process is incompletely understood. Current protocols for making primary astroglial cultures are inadequate for exploring the specific properties of white matter astrocytes in vitro. We describe a procedure for obtaining cultures of white matter astrocytes from the rodent corpus callosum. In this procedure, we take advantage of our previous finding that white, but not gray matter astrocytes express the calcium-binding protein S100A4. S100A4 expressing astrocytes are abundant in the corpus callosum, and we show that cultures, highly enriched in S100A4 expressing white matter astrocytes, can be reproducibly generated from this area. Key factors for successful cultures are (i) meticulous dissection of the corpus callosum from 4-day-old rats, and (ii) Percoll density gradient centrifugation to purify astrocytes. As a means of exploring the possible role of S100A4 in white matter astrocytes, we describe the use of the siRNA technique to eliminate the expression of S100A4 in our in vitro system.

  15. Soft-focused extracorporeal shock waves increase the expression of tendon-specific markers and the release of anti-inflammatory cytokines in an adherent culture model of primary human tendon cells.

    PubMed

    de Girolamo, Laura; Stanco, Deborah; Galliera, Emanuela; Viganò, Marco; Lovati, Arianna Barbara; Marazzi, Monica Gioia; Romeo, Pietro; Sansone, Valerio

    2014-06-01

    Focused extracorporeal shock waves have been found to upregulate the expression of collagen and to initiate cell proliferation in healthy tenocytes and to positively affect the metabolism of tendons, promoting the healing process. Recently, soft-focused extracorporeal shock waves have also been found to have a significant effect on tissue regeneration. However, very few in vitro reports have dealt with the application of this type of shock wave to cells, and in particular, no previous studies have investigated the response of tendon cells to this impulse. We devised an original model to investigate the in vitro effects of soft-focused shock waves on a heterogeneous population of human resident tendon cells in adherent monolayer culture. Our results indicate that soft-focused extracorporeal shock wave treatment (0.17 mJ/mm(2)) is able to induce positive modulation of cell viability, proliferation and tendon-specific marker expression, as well as release of anti-inflammatory cytokines. This could prefigure a new rationale for routine employment of soft-focused shock waves to treat the failed healing status that distinguishes tendinopathies. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  16. Response of periodontal ligament fibroblasts and gingival fibroblasts to pulsating fluid flow: nitric oxide and prostaglandin E2 release and expression of tissue non-specific alkaline phosphatase activity.

    PubMed

    van der Pauw, M T; Klein-Nulend, J; van den Bos, T; Burger, E H; Everts, V; Beertsen, W

    2000-12-01

    The capacity of the periodontal ligament to alter its structure and mass in response to mechanical loading has long been recognized. However, the mechanism by which periodontal cells can detect physical forces and respond to them is largely unknown. Besides transmission of forces via cell-matrix or cell-cell interactions, the strain-derived flow of interstitial fluid through the periodontal ligament may mechanically activate the periodontal cells, as well as ensure transport of cell signaling molecules, nutrients and waste products. Mechanosensory cells, such as endothelial and bone cells, are reported to respond to a flow of fluid with stimulated prostaglandin E2 (PGE2) and nitric oxide production. Therefore, we examined the PGE2 and nitric oxide response of human periodontal ligament and gingival fibroblasts to pulsating fluid flow and assessed the expression of tissue non-specific alkaline phosphatase activity. Periodontal ligament and gingival fibroblasts were subjected to a pulsating fluid flow (0.7 +/- 0.02 Pa, 5 Hz) for 60 min. PGE2 and nitric oxide concentrations were determined in the conditioned medium after 5, 10, 30 and 60 min of flowing. After fluid flow the cells were cultured for another 60 min without mechanical stress. Periodontal ligament fibroblasts, but not gingival fibroblasts, responded to fluid flow with significantly elevated release of nitric oxide and decreased expression of tissue non-specific alkaline phosphatase activity. In both periodontal ligament and gingival fibroblasts, PGE2 production was significantly increased after 60 min of flowing. Periodontal ligament fibroblasts, but not gingival fibroblasts, produced significantly higher levels of PGE2 during the postflow culture period. We conclude that human periodontal ligament fibroblasts are more responsive to pulsating fluid flow than gingival fibroblasts. The similarity of the early nitric oxide and PGE2 responses to fluid flow in periodontal fibroblasts with bone cells and

  17. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... at least annually for submission to the Past Performance Information Retrieval System (PPIRS), and... ADMINISTRATION AND AUDIT SERVICES Contractor Performance Information 2942.1503 Procedures. (a) In accordance with... criteria within their contracting activities. (d) Release of contractor performance evaluation...

  18. Releasable locking mechanisms

    NASA Technical Reports Server (NTRS)

    Ahmed, Rafiq (Inventor); Wingate, Robert J. (Inventor)

    2005-01-01

    In the aerospace field spacecraft components are held together by separation systems until a specific time when they must be separated or deployed. Customarily a threaded joining bolt engages one of the components to be joined, and a threaded nut is placed on that bolt against the other component so they can be drawn together by a releasable locking assembly. The releasable locking assembly herein includes a plunger having one end coupled to one end of a plunger bolt. The other end is flanged to abut and compress a coil spring when the plunger is advanced toward the interface plane between the two components. When the plunger is so advanced toward the interface plane, the end of the plunger bolt can be connected to the joining bolt. Thus during retraction the joining bolt is drawn to one side of the interface plane by the force of the expanding spring.

  19. Releasable Locking Mechanisms

    NASA Technical Reports Server (NTRS)

    Ahmed, Rafiq (Inventor); Wingate, Robert J. (Inventor)

    2005-01-01

    In the aerospace field spacecraft components are held together by separation systems until a specific time when they must be separated or deployed. Customarily a threaded joining bolt engages one of the components to be joined, and a threaded nut is placed on that bolt against the other component so they can be drawn together by a releasable locking assembly. The releasable locking assembly herein includes a plunger having one end coupled to one end of a plunger bolt. The other end is flanged to abut and compress a coil spring when the plunger is advanced toward the interface plane between the two components. When the plunger is so advanced toward the interface plane, the end of the plunger bolt can be connected to the joining bolt. Thus during retraction the joining bolt is drawn to one side of the interface plane by the force of the expanding spring.

  20. Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior.

    PubMed

    Bredewold, R; Schiavo, J K; van der Hart, M; Verreij, M; Veenema, A H

    2015-10-29

    Social play is a motivated and rewarding behavior that is displayed by nearly all mammals and peaks in the juvenile period. Moreover, social play is essential for the development of social skills and is impaired in social disorders like autism. We recently showed that the lateral septum (LS) is involved in the regulation of social play behavior in juvenile male and female rats. The LS is largely modulated by GABA and glutamate neurotransmission, but their role in social play behavior is unknown. Here, we determined whether social play behavior is associated with changes in the extracellular release of GABA and glutamate in the LS and to what extent such changes modulate social play behavior in male and female juvenile rats. Using intracerebral microdialysis in freely behaving rats, we found no sex difference in extracellular GABA concentrations, but extracellular glutamate concentrations are higher in males than in females under baseline conditions and during social play. This resulted in a higher glutamate/GABA concentration ratio in males vs. females and thus, an excitatory predominance in the LS of males. Furthermore, social play behavior in both sexes is associated with significant increases in extracellular release of GABA and glutamate in the LS. Pharmacological blockade of GABA-A receptors in the LS with bicuculline (100 ng/0.5 μl, 250 ng/0.5 μl) dose-dependently decreased the duration of social play behavior in both sexes. In contrast, pharmacological blockade of ionotropic glutamate receptors (NMDA and AMPA/kainate receptors) in the LS with AP-5+CNQX (2mM+0.4mM/0.5 μl, 30 mM+3mM/0.5 μl) dose-dependently decreased the duration of social play behavior in females, but did not alter social play behavior in males. Together, these data suggest a role for GABA neurotransmission in the LS in the regulation of juvenile social play behavior in both sexes, while glutamate neurotransmission in the LS is involved in the sex-specific regulation of juvenile social