Science.gov

Sample records for specification release procedure

  1. 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.

  2. 48 CFR 2905.404 - Release procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... release long-range acquisition estimates under the conditions in FAR 5.404-1. ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Release procedures. 2905.404 Section 2905.404 Federal Acquisition Regulations System DEPARTMENT OF LABOR ACQUISITION...

  3. Procedures for evaluating technical specifications

    SciTech Connect

    Boccio, J.L.; Robinson, R.C.; Samanta, P.K.; Vesely, W.E.

    1987-01-01

    The Procedures for Evaluating Technical Specifications (PETS) Program being conducted by Brookhaven National Laboratory for the Office of Research, US Nuclear Regulatory Commission (NRC), is developing various risk-based approaches for modifying Technical Specifications (TS). This paper highlights the various risk-based issues being addressed by the program and presents examples that exemplify the use of PRA models for modifying TS, primarily elements of the Limiting Condition of Operation (LCOs) and Surveillance Requirements (SRs). PETS approaches to TS modification using more detailed analysis are presented in a companion paper.

  4. 48 CFR 1305.404-1 - Release procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ACQUISITION PLANNING PUBLICIZING CONTRACT ACTIONS Release of Information 1305.404-1 Release procedures. The designee authorized to release long-range acquisition estimates is set forth in CAM 1301.70....

  5. An Evaluation and Comparison of Time-Out Procedures with and without Release Contingencies

    ERIC Educational Resources Information Center

    Donaldson, Jeanne M.; Vollmer, Timothy R.

    2011-01-01

    A common recommendation for implementing time-out procedures is to include a release contingency such that the individual is not allowed to leave time-out until no problem behavior has occurred for a specific amount of time (e.g, 30 s). We compared a fixed duration time-out procedure to a release contingency time-out procedure with 4 young…

  6. 19 CFR 142.48 - Release procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... measure, and the C-4 Code will be printed on the invoice and the manifest document and, when other agency documentation is presented, may be printed on that documentation. The invoice shall be returned to the entry.... The returned invoice with the release data shall be the release notification to non-ABI...

  7. 19 CFR 142.48 - Release procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... measure, and the C-4 Code will be printed on the invoice and the manifest document and, when other agency documentation is presented, may be printed on that documentation. The invoice shall be returned to the entry.... The returned invoice with the release data shall be the release notification to non-ABI...

  8. 19 CFR 142.48 - Release procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... documentation is presented, may be printed on that documentation. The invoice shall be returned to the entry.... (c) Notification to ABI participants. If the Line Release entry filer is an operational...

  9. 48 CFR 5.404-1 - Release procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PLANNING PUBLICIZING CONTRACT ACTIONS Release of Information 5.404-1 Release procedures. (a) Application. The agency head, or a designee, may release long-range acquisition estimates if the information will— (1) Assist industry in its planning and facilitate meeting the acquisition requirements; (2)...

  10. AN EVALUATION AND COMPARISON OF TIME-OUT PROCEDURES WITH AND WITHOUT RELEASE CONTINGENCIES

    PubMed Central

    Donaldson, Jeanne M; Vollmer, Timothy R

    2011-01-01

    A common recommendation for implementing time-out procedures is to include a release contingency such that the individual is not allowed to leave time-out until no problem behavior has occurred for a specific amount of time (e.g, 30 s). We compared a fixed-duration time-out procedure to a release contingency time-out procedure with 4 young children (3- and 4-year-olds) using a reversal and multielement design. Results demonstrated that both time-out procedures were effective at reducing problem behavior outside time-out, problem behavior occurred in time-out during both procedures, and problem behavior in time-out was not predictive of problem behavior outside time-out. PMID:22219523

  11. 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.

  12. 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 tasks--specifically,…

  13. 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... Licenses, Authorizations and Statements of Licensing Policy § 543.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E of this...

  14. 31 CFR 598.501 - 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... REGULATIONS Licenses, Authorizations, and Statements of Licensing Policy § 598.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E, of...

  15. 31 CFR 537.501 - 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... Licenses, Authorizations and Statements of Licensing Policy § 537.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart D, of this...

  16. 31 CFR 594.501 - 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... REGULATIONS Licenses, Authorizations and Statements of Licensing Policy § 594.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E, of...

  17. 31 CFR 535.501 - 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... Licenses, Authorizations and Statements of Licensing Policy § 535.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E, of this...

  18. 31 CFR 593.501 - 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... TAYLOR SANCTIONS REGULATIONS Licenses, Authorizations and Statements of Licensing Policy § 593.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part...

  19. 31 CFR 515.501 - 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... Licenses, Authorizations, and Statements of Licensing Policy § 515.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E, of this...

  20. 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... SANCTIONS REGULATIONS Licenses, Authorizations, and Statements of Licensing Policy § 547.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E...

  1. 31 CFR 588.501 - 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... REGULATIONS Licenses, Authorizations and Statements of Licensing Policy § 588.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E, of...

  2. 31 CFR 587.501 - 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... Licensing Policy § 587.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E, of this chapter. Licensing actions taken pursuant to part 501 of...

  3. 31 CFR 541.501 - 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... Licenses, Authorizations and Statements of Licensing Policy § 541.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart D, of this...

  4. 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... Licenses, Authorizations and Statements of Licensing Policy § 542.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E of this...

  5. 31 CFR 500.501 - 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... Licenses, Authorizations and Statements of Licensing Policy § 500.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E, of this...

  6. 31 CFR 546.501 - 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... Licenses, Authorizations, and Statements of Licensing Policy § 546.501 General and specific licensing procedures. For provisions relating to licensing procedures, see part 501, subpart E of this...

  7. Debulking procedures: potential device specific indications.

    PubMed

    Schwarzwälder, Uwe; Zeller, Thomas

    2010-03-01

    During the past decade, the endovascular treatment of peripheral arterial disease has become more widespread due to the impressive extension of the endovascular toolbox to include different atherectomy technologies. The promise of atherectomy is to avoid the "barotraumas" defined as complications of traditional angioplasty such as dissection, elastic recoil, and disruption of the internal elastic lamina resulting in overwhelming neointima and smooth muscle cell proliferation. The oldest atherectomy technologies are the excimer laser and the Rotablator. The excimer laser technology is based on the principle of photoablation converting occlusive material into microbubbles being immediately dissolved into the blood. The Rotablator and the newer diamondback device are high speed rotational "sanding" devices particularly developed for the treatment of highly calcified plaque particularly in small vessel lesions, such as the popliteal and infrapopliteal segments. The Silverhawk system, currently the most widespread used device, is a directional atherectomy device particularly designed for eccentric and not severely calcified infrainguinal lesions whereas a variation of this device, the Rockhawk, is dedicated for the treatment of calcified plaques. The Jetstream system is the latest approved rotational atherectomy device focusing on native arteries with a reference vessel diameter of 4-6 mm in its current version; uniquely this device also has an aspiration capability making the device not only an atherectomy device but potentially also a thrombectomy device. This article will review the different indications for the use of these atherectomy devices including tips and specific device limitations. PMID:20123432

  8. Specific release of plasma membrane enzymes by a phosphatidylinositol-specific phospholipase C.

    PubMed

    Low, M G; Finean, J B

    1978-04-20

    The release of plasma membrane ecto-enzymes by a phosphatidylinositol-specific phospholipase C from Staphylococcus aureus was investigated. There was no effect on L-leucyl-beta-naphthylamidase, alkaline phosphodeisterase I and Ca2+- or MG2+-ATPase, but substantial proportions of the alkaline phosphatase and 5-nucleotidase were released. There was no simultaneous release of phospholipid and the solubilized enzymes were not exluded from Sepharose 6-B. It was therefore concluded that release was not a secondary consequence of membrane vesiculation but occurred as a result of the disruption of specific interactions involving the phosphatidylinositol molecule.

  9. 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... (SERBIA & MONTENEGRO) KOSOVO SANCTIONS REGULATIONS Licenses, Authorizations, and Statements of Licensing Policy § 586.501 General and specific licensing procedures. For provisions relating to...

  10. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Once Customs releases the tobacco products or cigarette papers and tubes in accordance with 19 CFR Part... tubes in accordance with 19 CFR Part 143, Customs Directives, and any other applicable instructions, the..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND...

  11. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Once Customs releases the tobacco products or cigarette papers and tubes in accordance with 19 CFR Part..., 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...

  12. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Once Customs releases the tobacco products or cigarette papers and tubes in accordance with 19 CFR Part..., 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...

  13. 27 CFR 41.86 - Procedure for release.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Protection releases the tobacco products or cigarette papers and tubes in accordance with 19 CFR part 143... accordance with 19 CFR part 143, customs directives, and any other applicable instructions, the importer must..., DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  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 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...

  20. 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...

  1. 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...

  2. 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...

  3. 31 CFR 594.501 - 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. 594.501 Section 594.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM...

  4. 31 CFR 544.501 - 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. 544.501 Section 544.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS...

  5. 31 CFR 576.501 - 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. 576.501 Section 576.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND...

  6. 31 CFR 576.501 - 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. 576.501 Section 576.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND...

  7. 31 CFR 576.501 - 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. 576.501 Section 576.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND...

  8. 31 CFR 576.501 - 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. 576.501 Section 576.501 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND...

  9. 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

  10. 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…

  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

    ... 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... published on April 11, 2000 (65 FR 19476). FOR FURTHER INFORMATION CONTACT: Mr. Robert Redmond,...

  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... information system that serves as the clearinghouse and depository of information about the...

  13. 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.

  14. 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.

  15. 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

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

    PubMed

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

    2015-01-01

    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.

  17. A site-specific controlled-release system for metformin.

    PubMed

    Di Colo, Giacomo; Zambito, Ylenia; Baggiani, Andrea; Carelli, Vera; Serafini, Maria Francesca

    2005-05-01

    Oral absorption of the antihyperglycaemic agent metformin hydrochloride (MF-HCl) is confined to the upper part of the intestine, therefore rational controlled-release formulations of this drug should ensure a complete release during transit from stomach to jejunum. The aim of this study was the preparation of a system able to sustain release of high MF-HCl doses in compliance with the above requirement. Matrices (6 mm diameter; 50 mg weight) comprising varying drug-Precirol ATO 5 ratios were prepared by compression. The matrix containing 70% drug was coated on one face with Eudragit L100-55. Drug release to simulated gastric (SGF), jejunal (SJF) and ileal (SIF) fluids in sequence was studied using a modified USP rotating basket method. Release depended on drug load whereas it was independent of dissolution medium pH and hydrodynamics. Release kinetics were of radical t type and were determined by drug diffusion in aqueous pores created in the matrix by drug dissolution. An equation correlating rate-determining factors was developed, whereby the release pattern could be optimized. The half-coated matrix started release in SGF and completed it in SJF. The half-coated matrix, synchronizing drug release and matrix transit across the small intestine, may improve drug bioavailability and reduce side effects. PMID:15901345

  18. In vitro release of hydrocortisone from topical preparations and automated procedure.

    PubMed

    Shah, V P; Elkins, J; Hanus, J; Noorizadeh, C; Skelly, J P

    1991-01-01

    The in vitro drug release profile of hydrocortisone (HC) from creams, ointments, and lotions has been determined using an automated procedure. A diffusion cell system and commercially available synthetic membranes were utilized for the studies. The use of a synthetic membrane obviates the problems associated with using skin membranes. Uniform creams and ointment samples for determining release rate profile were prepared by using the teflon mask. Automated sampling avoids operator artifacts. The automated technique developed for determining the in vitro release rate profile of the drug from creams, ointments, and lotions using a diffusion-cell system appears to be a reasonable and practical procedure for assuring batch-to-batch uniformity of topical drug products.

  19. 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.

  20. Product Release Rather than Chelation Determines Metal Specificity for Ferrochelatase

    SciTech Connect

    Medlocka, Amy E.; Cartera, Michael; Daileya, Tamara A.; Daileya, Harry A.; Lanzilotta, William N.

    2009-11-16

    Ferrochelatase (protoheme ferrolyase, E.C. 4.99.1.1) is the terminal enzyme in heme biosynthesis and catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme IX (heme). Within the past two years, X-ray crystallographic data obtained with human ferrochelatase have clearly shown that significant structural changes occur during catalysis that are predicted to facilitate metal insertion and product release. One unanswered question about ferrochelatase involves defining the mechanism whereby some metals, such as divalent Fe, Co, Ni, and Zn, can be used by the enzyme in vitro to produce the corresponding metalloporphyrins, while other metals, such as divalent Mn, Hg, Cd, or Pb, are inhibitors of the enzyme. Through the use of high-resolution X-ray crystallography along with characterization of metal species via their anomalous diffraction, the identity and position of Hg, Cd, Ni, or Mn in the center of enzyme-bound porphyrin macrocycle were determined. When Pb, Hg, Cd, or Ni was present in the macrocycle, the conserved {pi} helix was in the extended, partially unwound 'product release' state. Interestingly, in the structure of ferrochelatase with Mn-porphyrin bound, the {pi} helix is not extended or unwound and is in the 'substrate-bound' conformation. These findings show that at least in the cases of Mn, Pb, Cd, and Hg, metal 'inhibition' of ferrochelatase is not due to the inability of the enzyme to insert the metal into the macrocycle or by binding to a second metal binding site as has been previously proposed. Rather, inhibition occurs after metal insertion and results from poor or diminished product release. Possible explanations for the lack of product release are proposed herein.

  1. Setting dissolution specifications for modified-release dosage forms.

    PubMed

    Piscitelli, D A; Young, D

    1997-01-01

    Dissolution specifications are used for quality assurance and may also serve as a surrogate for in vivo bioavailability. These limits can guide formulation development and eliminate the need for bioavailability studies for scale up and post approval changes. Several methods for setting dissolution specifications have been reviewed in this chapter. A summary of the advantages and disadvantages for each method can be found in Table 1. When choosing a method for setting dissolution specifications, it is important to 1) have a discriminating dissolution system, 2) incorporate in vivo data, 3) include intersubject variability, and 4) predict plasma concentration-time profiles. Predicting plasma concentration curves allows one to see how the change in formulation or dissolution limits perform in vivo. Dissolution specifications should be set so that all formulations that have dissolution profiles within the limits of the specifications are bioequivalent. This can be assured if the boundaries are tested for bioequivalence. Minimally, the formulations that have dissolution profiles within the limits of the specifications should be bioequivalent to the pivotal batch. A population prediction of the plasma concentration-time profiles for the upper and lower limit would incorporate the true intersubject variability for the formulation. PMID:9269491

  2. 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.

  3. 40 CFR Appendix E to Part 52 - Performance Specifications and, Specification Test Procedures for Monitoring Systems for Effluent...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....7Reference method. Method 2 as delineated in 40 CFR Part 60. 4. Measurement system performance specifications... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Performance Specifications and... 52—Performance Specifications and, Specification Test Procedures for Monitoring Systems for...

  4. 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

  5. Release of alkaline phosphatase from membranes by a phosphatidylinositol-specific phospholipase C.

    PubMed

    Low, M G; Finean, J B

    1977-10-01

    Purified phosphatidylinositol-specific phospholipase C from Staphylococcus aureus released a substantial proportion of the total alkaline phosphatase activity from a wide range of tissues from several mammalian species. Co-purification of the phospholipase C and alkaline phosphatase-releasing activities and the inhibition of both these activities by iso-osmotic salt solutions suggested that the releasing effect was unlikely to be due to a contaminant.

  6. [Specific anaesthetic procedures for nasal and sinus surgery].

    PubMed

    Boisson-Bertrand, D; Jacquot, C

    2014-12-01

    In nasal and sinus surgery, the anaesthetist must share the operating field with the surgeon and take into account some patients' specific pathologies. Bleeding must be avoided by different means but the accurate gesture of the surgeon, added to the properties of the new anaesthetic drugs, may reduce the risk of this functional surgery. PMID:25458457

  7. 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…

  8. 40 CFR Appendix E to Part 52 - Performance Specifications and, Specification Test Procedures for Monitoring Systems for Effluent...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....7Reference method. Method 2 as delineated in 40 CFR Part 60. 4. Measurement system performance specifications..., Specification Test Procedures for Monitoring Systems for Effluent Stream Gas Volumetric Flow Rate E Appendix E... Stream Gas Volumetric Flow Rate 1. Principle and applicability. 1.1Principle. Effluent stream...

  9. 40 CFR Appendix E to Part 52 - Performance Specifications and, Specification Test Procedures for Monitoring Systems for Effluent...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....7Reference method. Method 2 as delineated in 40 CFR Part 60. 4. Measurement system performance specifications..., Specification Test Procedures for Monitoring Systems for Effluent Stream Gas Volumetric Flow Rate E Appendix E... Stream Gas Volumetric Flow Rate 1. Principle and applicability. 1.1Principle. Effluent stream...

  10. 40 CFR Appendix E to Part 52 - Performance Specifications and, Specification Test Procedures for Monitoring Systems for Effluent...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....7Reference method. Method 2 as delineated in 40 CFR Part 60. 4. Measurement system performance specifications..., Specification Test Procedures for Monitoring Systems for Effluent Stream Gas Volumetric Flow Rate E Appendix E... Stream Gas Volumetric Flow Rate 1. Principle and applicability. 1.1Principle. Effluent stream...

  11. 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.

  12. Endogenous glycosylphosphatidylinositol-specific phospholipase C releases renal dipeptidase from kidney proximal tubules in vitro.

    PubMed

    Park, S W; Choi, K; Kim, I C; Lee, H H; Hooper, N M; Park, H S

    2001-01-15

    Spontaneous enzymic release of renal dipeptidase (RDPase; EC 3.4.13.19), a glycosylphosphatidylinositol (GPI)-linked ectoenzyme, was observed in vitro during incubation of porcine proximal tubules at 37 degrees C. Triton X-114 phase separation of the released RDPase showed that the majority of the enzyme activity partitioned into the aqueous phase, indicating its hydrophilic nature. Immunoblot analyses using an antibody against the cross-reacting determinant (CRD) inositol 1,2-cyclic monophosphate, the epitope formed by phospholipase C (PLC) cleavage of the GPI anchor on a protein, detected the released RDPase. Reprobing the immunoblot with an anti-RDPase serum showed the RDPase band co-migrating with the CRD band. The release of RDPase from the proximal tubules was a Ca(2+)-dependent process and had a pH optimum of 9.0. These results indicate that RDPase is released from the proximal tubules by the action of a distinct endogenous GPI-specific PLC.

  13. 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...

  14. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  15. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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...

  16. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  17. 33 CFR 157.420 - Vessel specific watch policy and procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SECURITY (CONTINUED) POLLUTION RULES FOR THE PROTECTION OF THE MARINE ENVIRONMENT RELATING TO TANK VESSELS... vessel specific watchkeeping, safety, environmental protection, and emergency procedures and arrangements... employed individual to receive essential information in a language the individual understands....

  18. 40 CFR Appendix E to Part 52 - Performance Specifications and, Specification Test Procedures for Monitoring Systems for Effluent...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....7Reference method. Method 2 as delineated in 40 CFR Part 60. 4. Measurement system performance specifications... conditioning. Set up and operate the measurement system in accordance with the manufacturer's written...'s specified zero and calibration procedures, if appropriate. Record the measurement system...

  19. 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

  20. 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.

  1. 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. PMID:26848056

  2. 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.

  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. PMID:26264832

  4. A simple and effective procedure for treating burn contractures: releasing incision and quadra Z technique.

    PubMed

    Sen, Cenk; Karacalar, Ahmet; Agir, Hakan; Dinar, Serkan; Isil, Eda; Iscen, Deniz

    2007-03-01

    Burn contractures particularly involving the joints are challenging problems which might cause severe functional impairments. Many surgical techniques have been described for use, however, an ideal method yet to be found. Releasing incision is the most common and effective way to release the wide and severe contractures but it has some drawbacks. We propose a releasing incision technique combined with four Z plasty incisions to overcome the disadvantages of traditional releasing incision technique. We successfully used our releasing incision and quadra Z technique on seven consecutive patients with burn contractures between 2003 and 2005. We modified the classical releasing incision technique by adding four Z plasties; two of them with a common base on each corner of the incision line. In this technique, limitation of the webbing following the incision is made possible by the transposed flaps and unnecessary lateral extension of the incision and the defect was avoided, i.e. maximum release gain with minimal defect was provided. Satisfactory results were achieved in seven patients treated with this technique due to significant burn contractures between 2003 and 2005 with no significant complication. We propose this technique is suitable in all patients with severe burn contractures who require releasing incision and grafting.

  5. Bristow-Latarjet procedure with specific instrumentation: study of 34 cases

    PubMed Central

    Debet-Mejean, A.; Chetboun, A.; Nourissat, G.

    2008-01-01

    A Bristow-Latarjet procedure with specific instrumentation was performed for recurrent dislocation or subluxation of the glenohumeral joint in 34 patients. The procedure was performed through a subscapularis splitting approach with three specific instruments and a special screw. The clinical outcome was assessed by the Duplay and the Constant scores. Radiographic study was conducted on 23 patients and CT scan in 11 patients. Of the 27 patients interviewed 92% were satisfied. Of the 23 patients examined, 15 had an excellent Duplay score, four a good score, three a medium score, and only one had a bad score. One patient had subluxation episodes, and one patient was revised after a redislocation following violent trauma. On the standard radiographs, all bone blocks were in the correct position. A pseudarthrosis was diagnosed in the patient with subluxation episodes. This device simplifies the surgical technique and provides reproducibility to the procedure. PMID:18633611

  6. 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…

  7. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 type room heaters and fireplace stoves. (a) Applicable standards. Solid fuel type room heaters...

  8. 14 CFR 93.352 - Hudson River Exclusion specific operating procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Hudson River Exclusion specific operating procedures. 93.352 Section 93.352 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

  9. 14 CFR 93.353 - East River Exclusion specific operating procedures.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false East River Exclusion specific operating procedures. 93.353 Section 93.353 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

  10. 14 CFR 93.353 - East River Exclusion specific operating procedures.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false East River Exclusion specific operating procedures. 93.353 Section 93.353 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

  11. 14 CFR 93.353 - East River Exclusion specific operating procedures.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false East River Exclusion specific operating procedures. 93.353 Section 93.353 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

  12. 14 CFR 93.352 - Hudson River Exclusion specific operating procedures.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Hudson River Exclusion specific operating procedures. 93.352 Section 93.352 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

  13. 14 CFR 93.352 - Hudson River Exclusion specific operating procedures.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Hudson River Exclusion specific operating procedures. 93.352 Section 93.352 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

  14. 14 CFR 93.352 - Hudson River Exclusion specific operating procedures.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Hudson River Exclusion specific operating procedures. 93.352 Section 93.352 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

  15. 14 CFR 93.353 - East River Exclusion specific operating procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false East River Exclusion specific operating procedures. 93.353 Section 93.353 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES New York Class...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... subject to emission limits for mercury and hydrogen chloride in Tables 1, 2, or 12 to this subpart... fuel specification analyses for hydrogen sulfide and mercury according to the procedures in paragraphs... common point of gas distribution. (iv) For each fuel type, the analytical methods from Table 6, with...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... subject to emission limits for mercury and hydrogen chloride in Tables 1, 2, or 12 to this subpart... fuel specification analyses for hydrogen sulfide and mercury according to the procedures in paragraphs... common point of gas distribution. (iv) For each fuel type, the analytical methods from Table 6, with...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Supplementary specific procedural 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 200.937 Housing and Urban...

  1. 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.

  2. Patient-specific treatment planning of electrochemotherapy: procedure design and possible pitfalls.

    PubMed

    Pavliha, Denis; Kos, Bor; Zupanič, Anže; Marčan, Marija; Serša, Gregor; Miklavčič, Damijan

    2012-10-01

    Electrochemotherapy uses electroporation for enhancing chemotherapy. Electrochemotherapy can be performed using standard operating procedures with predefined electrode geometries, or using patient-specific treatment planning to predict electroporation. The latter relies on realistic computer models to provide optimal results (i.e. electric field distribution as well as electrodes' position and number) and is suitable for treatment of deep-seated tumors. Since treatment planning for deep-seated tumors has been used in radiotherapy, we expose parallelisms with radiotherapy in order to establish the procedure for electrochemotherapy of deep-seated tumors. We partitioned electrochemotherapy in the following phases: the mathematical model of electroporation, treatment planning, set-up verification, treatment delivery and monitoring, and response assessment. We developed a conceptual treatment planning software that incorporates mathematical models of electroporation. Preprocessing and segmentation of the patient's medical images are performed, and a 3D model is constructed which allows placement of electrodes and implementation of the mathematical model of electroporation. We demonstrated the feasibility of electrochemotherapy of deep-seated tumors treatment planning within a clinical study where treatment planning contributed to the effective electrochemotherapy treatment of deep-seated colorectal metastases in the liver. The described procedure can provide medical practitioners with information on using electrochemotherapy in the clinical setting. The main aims of this paper are: 1) to present the procedure for treating deep-seated tumors by electrochemotherapy based on patient-specific treatment planning, and 2) to identify gaps in knowledge and possible pitfalls of such procedure.

  3. 50 CFR Appendix F to Part 622 - Specifications for Sea Turtle Mitigation Gear and Sea Turtle Handling and Release Requirements

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Specifications for Sea Turtle Mitigation Gear and Sea Turtle Handling and Release Requirements F Appendix F to Part 622 Wildlife and Fisheries...—Specifications for Sea Turtle Mitigation Gear and Sea Turtle Handling and Release Requirements A. Sea...

  4. 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...

  5. Antigen-Specific IP-10 Release Is a Sensitive Biomarker of Mycobacterium bovis Infection in Cattle.

    PubMed

    Parsons, Sven D C; McGill, Kevina; Doyle, Mairead B; Goosen, Wynand J; van Helden, Paul D; Gormley, Eamonn

    2016-01-01

    The most widely used ante-mortem diagnostic tests for tuberculosis in cattle are the tuberculin skin test and the interferon-gamma (IFN-γ) release assay, both of which measure cell-mediated immune responses to Mycobacterium bovis infection. However, limitations in the performance of these tests results in a failure to identify all infected animals. In attempting to increase the range of diagnostic tests for tuberculosis, measurement of the cytokine IP-10 in antigen-stimulated blood has previously been shown to improve the detection of M. tuberculosis and M. bovis infection, in humans and African buffaloes (Syncerus caffer), respectively. In the present study, 60 cattle were identified by the single intradermal comparative tuberculin test as tuberculosis reactors (n = 24) or non-reactors (n = 36) and the release of IFN-γ and IP-10 in antigen-stimulated whole blood from these animals was measured using bovine specific ELISAs. There was a strong correlation between IP-10 and IFN-γ production in these samples. Moreover, measurement of the differential release of IP-10 in response to stimulation with M. bovis purified protein derivative (PPD) and M. avium PPD distinguished between reactor and non-reactor cattle with a sensitivity of 100% (95% CI, 86%-100%) and a specificity of 97% (95% CI, 85%-100%). These results suggest that IP-10 might prove valuable as a diagnostic biomarker of M. bovis infection in cattle. PMID:27167122

  6. Patient-specific simulations of stenting procedures in coronary bifurcations: two clinical cases.

    PubMed

    Morlacchi, Stefano; Colleoni, Sebastian George; Cárdenes, Rubén; Chiastra, Claudio; Diez, Jose Luis; Larrabide, Ignacio; Migliavacca, Francesco

    2013-09-01

    Computational simulations of stenting procedures in idealized geometries can only provide general guidelines and their use in the patient-specific planning of percutaneous treatments is inadequate. Conversely, image-based patient-specific tools that are able to realistically simulate different interventional options might facilitate clinical decision-making and provide useful insights on the treatment for each individual patient. The aim of this work is the implementation of a patient-specific model that uses image-based reconstructions of coronary bifurcations and is able to replicate real stenting procedures following clinical indications. Two clinical cases are investigated focusing the attention on the open problems of coronary bifurcations and their main treatment, the provisional side branch approach. Image-based reconstructions are created combining the information from conventional coronary angiography and computed tomography angiography while structural finite element models are implemented to replicate the real procedure performed in the patients. First, numerical results show the biomechanical influence of stents deployment in the coronary bifurcations during and after the procedures. In particular, the straightening of the arterial wall and the influence of two overlapping stents on stress fields are investigated here. Results show that a sensible decrease of the vessel tortuosity occurs after stent implantation and that overlapping devices result in an increased stress state of both the artery and the stents. Lastly, the comparison between numerical and image-based post-stenting configurations proved the reliability of such models while replicating stent deployment in coronary arteries.

  7. Development of a patient-specific surgical simulator for pediatric laparoscopic procedures.

    PubMed

    Saber, Nikoo R; Menon, Vinay; St-Pierre, Jean C; Looi, Thomas; Drake, James M; Cyril, Xavier

    2014-01-01

    The purpose of this study is to develop and evaluate a pediatric patient-specific surgical simulator for the planning, practice, and validation of laparoscopic surgical procedures prior to intervention, initially focusing on the choledochal cyst resection and reconstruction scenario. The simulator is comprised of software elements including a deformable body physics engine, virtual surgical tools, and abdominal organs. Hardware components such as haptics-enabled hand controllers and a representative endoscopic tool have also been integrated. The prototype is able to perform a number of surgical tasks and further development work is under way to simulate the complete procedure with acceptable fidelity and accuracy. PMID:24732536

  8. 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.

  9. 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.

  10. 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. PMID:18508275

  11. A ligand-specific action of chelated copper on hypothalamic neurons: stimulation of the release of luteinizing hormone-releasing hormone from median eminence explants.

    PubMed Central

    Barnea, A; Colombani-Vidal, M

    1984-01-01

    We have previously shown that chelated copper stimulates the release of luteinizing hormone-releasing hormone (LHRH) from isolated hypothalamic granules. In this study, we wished to ascertain if chelated copper acts on hypothalamic neurons to stimulate LHRH release and, if so, what is the ligand specificity of this interaction. An in vitro system of explants of the median eminence area (MEA) was established and characterized. MEA explants were exposed for 15 min to 50 microM copper, and then they were incubated for 75 min in copper-free medium. Copper led to a transient increase in the rate of LHRH release; the maximal rate was attained 15 min after transfer of the MEA to copper-free medium. In addition, we found that copper complexed to histidine (Cu-His), but not ionic copper, stimulated LHRH release, the magnitude of which was dependent on the dose of Cu-His. The chelator specificity for Cu complex action was such that Cu-His stimulated LHRH release 4.9-fold and Cu-Cys stimulated release 2.5-fold, whereas neither Cu-Thr, Cu-Gly-His-Lys, Cu-bovine serum albumin, nor ceruloplasmin stimulated LHRH release. Based on these results and those of others indicating that the concentration of copper in hypothalamic axonal terminals is 1-2 orders of magnitude greater than plasma, we propose that copper released in the vicinity of the LHRH neurons interacts with specific sites on the LHRH axonal terminals, which leads to release of the peptide. PMID:6390443

  12. 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.

  13. Selective release of plasma-membrane enzymes from rat hepatocytes by a phosphatidylinositol-specific phospholipase C.

    PubMed

    Shukla, S D; Coleman, R; Finean, J B; Michell, R H

    1980-04-01

    When isolated hepatocytes are incubated with phosphatidylinositol-specific phospholipase C, three cell-surface enzymes show markedly different behaviour. Most of the alkaline phosphatase is released at very low values of phosphatidylinositol hydrolysis, whereas further phosphatidylinositol hydrolysis releases only a maximum of about one-third of the 5'-nucleotidase. Alkaline phosphodiesterase I is not released. If cells containing phosphatidyl[3H]inositol are similarly treated, then the released [3H]inositol is in the form of inositol phosphate: no evidence has been obtained for any covalent association between released [3H]inositol and alkaline phosphatase.

  14. Prediction of patient-specific post-operative outcomes of TAVI procedure: The impact of the positioning strategy on valve performance.

    PubMed

    Morganti, S; Brambilla, N; Petronio, A S; Reali, A; Bedogni, F; Auricchio, F

    2016-08-16

    Prosthesis positioning in transcatheter aortic valve implantation procedures represents a crucial aspect for procedure success as demonstrated by many recent studies on this topic. Possible complications, device performance, and, consequently, also long-term durability are highly affected by the adopted prosthesis placement strategy. In the present work, we develop a computational finite element model able to predict device-specific and patient-specific replacement procedure outcomes, which may help medical operators to plan and choose the optimal implantation strategy. We focus in particular on the effects of prosthesis implantation depth and release angle. We start from a real clinical case undergoing Corevalve self-expanding device implantation. Our study confirms the crucial role of positioning in determining valve anchoring, replacement failure due to intra or para-valvular regurgitation, and post-operative device deformation.

  15. 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

  16. 32 CFR 1656.16 - Early release-grounds and procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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. An... based on a physical or mental examination at a MEPS or other location designated by Selective...

  17. 32 CFR 1656.16 - Early release-grounds and procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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. An... based on a physical or mental examination at a MEPS or other location designated by Selective...

  18. 32 CFR 1656.16 - Early release-grounds and procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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. An... based on a physical or mental examination at a MEPS or other location designated by Selective...

  19. 32 CFR 1656.16 - Early release-grounds and procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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. An... based on a physical or mental examination at a MEPS or other location designated by Selective...

  20. 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.

  1. 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. PMID:6406240

  2. 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

  3. 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.

  4. Scalable Imprinting of Shape-Specific Polymeric Nanocarriers Using a Release Layer of Switchable Water Solubility

    PubMed Central

    Agarwal, Rachit; Singh, Vikramjit; Jurney, Patrick; Shi, Li; Sreenivasan, S. V.; Roy, Krishnendu

    2012-01-01

    There is increasing interest in fabricating shape-specific polymeric nano and microparticles for efficient delivery of drugs and imaging agents. The size and shape of these particles could significantly influence their transport properties and play an important role in in vivo biodistribution, targeting and cellular uptake. Nanoimprint lithography methods, such as Jet-and-flash imprint lithography (J-FIL), provide versatile top-down processes to fabricate shape-specific, biocompatible nanoscale hydrogels that can deliver therapeutic and diagnostic molecules in response to disease-specific cues. However, the key challenges in top-down fabrication of such nanocarriers are scalable imprinting with biological and biocompatible materials, ease of particle-surface modification using both aqueous and organic chemistry as well as simple yet biocompatible harvesting. Here we report that a biopolymer-based sacrificial release layer in combination with improved nanocarrier-material formulation can address these challenges. The sacrificial layer improves scalability and ease of imprint-surface modification due to its switchable solubility through simple ion exchange between monovalent and divalent cations. This process enables large-scale bio-nanoimprinting and efficient, one-step harvesting of hydrogel nanoparticles in both water- and organic-based imprint solutions. PMID:22385068

  5. A specific radioimmunoassay for corticotropin releasing factor (CRF) using synthetic ovine CRF. [Rats

    SciTech Connect

    Hashimoto, K.; Murakami, K.; Ohno, N.; Kageyama, J.; Aoki, Y.; Takahara, J.; Ota, Z.

    1983-02-28

    This newly developed specific radioimmunoassay for corticotropin releasing factor (CRF) had a sensitivity range of 25 pg/tube to 4 ng/tube. Intra and interassay coefficients of variation were 4.6% and 9.8%, respectively. Rat median eminence extracts showed a parallel dose response curve with synthetic ovine CRF and a significant cross reaction was not evident with other tested neuropeptides. The highest mean levels of CRF were found in the median eminence (6.61 ng/mg proparaventricular nucleus, dorsomedial nucleus, suprachiasmatic nucleus and ventromedial nucleus. The immunoreactive CRF of the rat medial basal hypothalamus coeluted with bioassayable CRF and with iodinated CRF on Sephadex G-75 chromatography. The results indicate that rat hypothalamus contains a CRF similar to ovine CRF.

  6. Targeted diazeniumdiolates: localized nitric oxide release from glioma-specific peptides and proteins.

    PubMed

    Safdar, Shahana; Taite, Lakeshia J

    2012-01-17

    Nitric oxide (NO) is a small yet important biological messenger, which at sufficient concentrations has been shown to induce apoptosis as well as increase radiosensitization in tumor cells. However, the short half-life of NO gas itself has limited its utility as a therapeutic agent. The objective of this study was the development of targeted NO donors and we illustrate their utility as a potential therapeutic for treatment of glioblastoma multiforme, the most common and aggressive malignant primary brain tumor in adults. We have synthesized two diazeniumdiolate NO donors by reacting NO gas with glioma-specific targeting sequences, VTWTPQAWFQWVGGGSKKKKK (VTW) and chlorotoxin (CTX), and achieved repeatable NO release from both donors. FITC-labeled biomolecules, when incubated with glioma and control cells preferentially bound to the glioma cells and showed only minimal binding to the control cells. Additionally, tumor cell viability was significantly decreased when cells were incubated with the NO donors whereas control cell viability was not affected.

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

    PubMed Central

    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.

    2016-01-01

    Summary Objectives 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. Methods 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. Results 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). Conclusions Our data shows the potential to population tailor detection of MTB sensitization using specific synthetic peptides and interferon-gamma release in vitro. PMID:26632326

  8. 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.

  9. 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

  10. Towards patient-specific finite-element simulation of MitralClip procedure.

    PubMed

    Mansi, T; Voigt, I; Assoumou Mengue, E; Ionasec, R; Georgescu, B; Noack, T; Seeburger, J; Comaniciu, D

    2011-01-01

    MitralClip is a novel minimally invasive procedure to treat mitral valve (MV) regurgitation. It consists in clipping the mitral leaflets together to close the regurgitant hole. A careful preoperative planning is necessary to select respondent patients and to determine the clipping sites. Although preliminary indications criteria are established, they lack prediction power with respect to complications and effectiveness of the therapy in specific patients. We propose an integrated framework for personalized simulation of MV function and apply it to simulate MitralClip procedure. A patient-specific dynamic model of the MV apparatus is computed automatically from 4D TEE images. A biomechanical model of the MV, constrained by the observed motion of the mitral annulus and papillary muscles, is employed to simulate valve closure and MitralClip intervention. The proposed integrated framework enables, for the first time, to quantitatively evaluate an MV finite-element model in-vivo, on eleven patients, and to predict the outcome of MitralClip intervention in one of these patients. The simulations are compared to ground truth and to postoperative images, resulting in promising accuracy (average point-to-mesh distance: 1.47 +/- 0.24 mm). Our framework may constitute a tool for MV therapy planning and patient management.

  11. Detection of Mycobacterium avium subsp. paratuberculosis in Infected Tissues by New Species-Specific Immunohistological Procedures

    PubMed Central

    Coetsier, Christophe; Havaux, Xavier; Mattelard, Francois; Sadatte, Sanaa; Cormont, Francoise; Buergelt, Klaus; Limbourg, Bernard; Latinne, Dominique; Bazin, Herve; Denef, Jean-Francois; Cocito, Carlo

    1998-01-01

    We have previously described the cloning and sequencing of a gene portion coding for the terminal part of a 34-kDa protein of Mycobacterium avium subsp. paratuberculosis, the etiological agent of Johne’s disease (P. Gilot, M. De Kesel, L. Machtelinckx, M. Coene, and C. Cocito, J. Bacteriol. 175:4930–4935, 1993). The recombinant polypeptide (a362) carries species-specific B-cell epitopes which do not cross-react with other mycobacterial pathogens (M. De Kesel, P. Gilot, M.-C. Misonne, M. Coene, and C. Cocito, J. Clin. Microbiol. 31:947–954, 1993). The present work describes the preparation of polyclonal and monoclonal antibodies directed against a362 and the use of these immunoglobulins for histopathological diagnosis of Johne’s disease. The new immunohistological procedures herewith detailed proved to be able to identify M. avium subsp. paratuberculosis antigens in the intestinal tissues and lymph nodes of cattle affected by either the paucibacillary or pluribacillary form of the disease. They yielded negative responses not only with healthy animals but also with those affected by tuberculosis (Mycobacterium bovis). Both immunohistological procedures proved to be as sensitive as or more sensitive than Ziehl-Neelsen staining and, in addition, to be endowed with species specificity. PMID:9665946

  12. 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

    2012-01-01

    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.

  13. 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.

  14. [Study on phase distribution and release of heavy metal in pyrite using sequential extraction procedure and ICP-MS].

    PubMed

    Zhang, Ping; Qi, Jian-Ying; Yang, Chun-Xia; Chen, Yong-Heng

    2007-06-01

    Heavy metal elements of V, Cr, Mn, Co, Ni, Cu, Zn, Sr, Mo, Cd, Sb, Ba and Pb were determined by ICP-MS. The linear ranges of determination for these elements were obtained, and the correlation coefficients were larger than 0.997. The detection limit ranges were from 0.005 to 0.01 microg x L(-1) and the RSDs were lower than 5%. Phase distributions of heavy metals in pyrite were analyzed by ICP-MS with sequential extraction procedure. The result showed that Pb was the main heavy metal in pyrite and its total content was 830 mg x kg(-1). Pb existed mostly in carbonate or galena (PbS) phase of pyrite and the proportion was 56.9%. Pb existed less in iron oxides with 29.7% in proportion, and least in sulfide and silicate with 3.5% and 9.9%, respectively. The release of Pb in pyrite was primary in natural environment, but the release of Cr and Cd was not be ignorable, too. PMID:17763794

  15. 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

  16. Cocaine and specific cocaine metabolites induce von Willebrand Factor release from endothelial cells in a tissue-specific manner

    PubMed Central

    Hobbs, William E.; Moore, Emily E.; Penkala, Rebecca A.; Bolgiano, D.; López, José A.

    2013-01-01

    Objective Cocaine use is associated with arterial thrombosis, including myocardial infarction and stroke. Cocaine use results in increased plasma von Willebrand Factor (VWF), accelerated atherosclerosis, and platelet-rich arterial thrombi, suggesting that cocaine activates the endothelium, promoting platelet-VWF interactions. Approach and Results Human umbilical vein (HUVEC), brain microvasculature (BMVEC), or coronary artery (CAEC) endothelial cells were treated with cocaine or metabolites benzoylecgonine, cocaethylene, norcocaine, or ecgonine methylester. Supernatant VWF concentration and multimer structure were measured, and platelet–VWF strings formed on the endothelial surface under flow were quantified. Cocaine, benzoylecgonine, and cocaethylene induced endothelial VWF release, with the two metabolites being more potent than the parent molecule. BMVEC were more sensitive to cocaine and metabolites than were HUVEC or CAEC. CAEC released VWF into the supernatant but did not form VWF–platelet strings. Intracellular cAMP concentration was not increased after treatment with cocaine or its metabolites. Conclusions Both cocaine and metabolites benzoylecgonine and cocaethylene induced endothelial VWF secretion, possibly explaining thrombotic risk after cocaine ingestion. VWF secretion is likely to vary between vascular beds, with brain endothelial cells being particularly sensitive. These results suggest that clinical management of cocaine-induced ischemia may benefit from therapies aimed at disrupting the VWF–platelet interaction. PMID:23539221

  17. 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.

  18. 50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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...

  19. 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...

  20. 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...

  1. 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...

  2. 50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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...

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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.

  4. 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.

  5. 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 Central

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

    2014-01-01

    Background Using blood utilization data acquired from our anesthesia information management system, an updated institution-specific maximum surgical blood order schedule (MSBOS) was introduced. We evaluate whether the MSBOS, along with a remote electronic blood release system (EBRS), reduced unnecessary preoperative blood orders and costs. Methods 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 MSBOS and the EBRS (Hemosafe®, Haemonetics Corp., Braintree, MA) were introduced mid-way through this time period. We assessed whether these interventions led to reductions in unnecessary preoperative orders and associated costs. Results Among patients having surgical procedures deemed not to require a type and screen or crossmatch (n = 33,216), the percentage 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/patient) for surgical patients, and by $298,966 ($6.20/patient) for all hospitalized patients. Conclusions Implementing institution-specific, updated MSBOS-directed preoperative blood ordering guidelines along with an EBRS results in a substantial reduction in unnecessary orders and costs, with a clinically insignificant increase in requirement for emergency release blood transfusions. PMID:24932853

  6. A procedure for selective full length cDNA cloning of specific RNA species.

    PubMed Central

    Schmid, A; Cattaneo, R; Billeter, M A

    1987-01-01

    A method allowing routine establishment of full length and functionally competent cDNA clones of particular mRNAs from small preparations of polyadenylated RNA is described. Pairs of synthetic primers are used for first and second strand synthesis. They include sequences complementary to the 3' terminal regions of the mRNAs and of the full length first cDNA strands, respectively and bear a few additional nucleotides at their 5' ends. After synthesis of both cDNA strands in one tube, they are precisely trimmed back with T4 DNA polymerase in presence of only two nucleoside triphosphates, to yield sticky ends fitting into a vector plasmid cleaved with two restriction endonucleases. The procedure was first applied to the simultaneous cloning of all five major measles virus (MV) mRNA species from a persistently infected cell line. Two thirds of all clones contained full length MV-specific cDNAs. Screening of less than 200 clones was sufficient to obtain several independent clones corresponding to each mRNA, except for gene F which was represented only once. Images PMID:2884622

  7. 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

  8. A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery.

    PubMed

    Fine, Daniel; Grattoni, Alessandro; Hosali, Sharath; Ziemys, Arturas; De Rosa, Enrica; Gill, Jaskaran; Medema, Ryan; Hudson, Lee; Kojic, Milos; Milosevic, Miljan; Brousseau Iii, Louis; Goodall, Randy; Ferrari, Mauro; Liu, Xuewu

    2010-11-21

    This manuscript demonstrates a mechanically robust implantable nanofluidic membrane capable of tunable long-term zero-order release of therapeutic agents in ranges relevant for clinical applications. The membrane, with nanochannels as small as 5 nm, allows for the independent control of both dosage and mechanical strength through the integration of high-density short nanochannels parallel to the membrane surface with perpendicular micro- and macrochannels for interfacing with the ambient solutions. These nanofluidic membranes are created using precision silicon fabrication techniques on silicon-on-insulator substrates enabling exquisite control over the monodispersed nanochannel dimensions and surface roughness. Zero-order release of analytes is achieved by exploiting molecule to surface interactions which dominate diffusive transport when fluids are confined to the nanoscale. In this study we investigate the nanofluidic membrane performance using custom diffusion and gas testing apparatuses to quantify molecular release rate and process uniformity as well as mechanical strength using a gas based burst test. The kinetics of the constrained zero-order release is probed with molecules presenting a range of sizes, charge states, and structural conformations. Finally, an optimal ratio of the molecular hydrodynamic diameter to the nanochannel dimension is determined to assure zero-order release for each tested molecule.

  9. 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.

  10. 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.

  11. 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

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false May the authorized official use both type A and type B procedures for the same release? 11.36 Section 11.36 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE ASSESSMENTS Assessment Plan Phase § 11.36...

  12. 43 CFR 11.36 - May the authorized official use both type A and type B procedures for the same release?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false May the authorized official use both type A and type B procedures for the same release? 11.36 Section 11.36 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE ASSESSMENTS Assessment Plan Phase § 11.36...

  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. Intestine-Specific, Oral Delivery of Captopril/Montmorillonite: Formulation and Release Kinetics

    PubMed Central

    2011-01-01

    The intercalation of captopril (CP) into the interlayers of montmorillonite (MMT) affords an intestine-selective drug delivery system that has a captopril-loading capacity of up to ca. 14 %w/w and which exhibits near-zero-order release kinetics. PMID:27502639

  15. PREVENTION REFERENCE MANUAL: CHEMICAL SPECIFIC, VOLUME 13: CONTROL OF ACCIDENTAL RELEASES OF METHYL ISOCYANATE

    EPA Science Inventory

    This is one of a series of manuals addressing accidental releases of toxic chemicals. Methyl isocyanite (MIC) has an Immediately Dangerous to Life and Health (IDLH) concentration of 20 ppm, making it a substantially acute toxic hazard. Reducing the risk associated with an acciden...

  16. 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. PMID:27578923

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

    PubMed Central

    Zanotto, Camila Ziliotto

    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. PMID:27578923

  18. Inhibition of ACh release at an Aplysia synapse by neurotoxic phospholipases A2: specific receptors and mechanisms of action.

    PubMed Central

    Fossier, P; Lambeau, G; Lazdunski, M; Baux, G

    1995-01-01

    1. Monochain (OS2) and multichain (taipoxin) neurotoxic phospholipases A2 (PLA2), purified from taipan snake venom, both inhibited ACh release at a concentration of 20 nM (90% inhibition in 2 h) at an identified synapse from buccal ganglion of Aplysia californica. 2. The Na+ current was unchanged upon application of either OS2 or taipoxin. Conversely, presynaptic K+ currents (IA and IK) were increased by taipoxin but not by OS2. In addition, OS2 induced a significant decrease of the presynaptic Ca2+ current (30%) while taipoxin increased this latter current by 20-30%. 3. Bee venom PLA2, another monochain neurotoxic PLA2, also inhibited ACh release while non-toxic enzymatically active PLA2s like OS1 (also purified from taipan snake venom) or porcine pancreatic PLA2 elicited a much weaker inhibition of ACh release, suggesting a specific action of neurotoxic PLA2s versus non-toxic PLA2s on ACh release. 4. Using iodinated OS2, specific high affinity binding sites with molecular masses of 140 and 18 kDa have been identified on Aplysia ganglia. The maximal binding capacities were 55 and 300-400 fmol (mg protein)-1 for membrane preparations from whole and buccal ganglia, respectively. These binding sites are of high affinity for neurotoxic PLA2s (Kd values, 100-800 pM) and of very low affinity for non-toxic PLA2s (Kd values in the micromolar range), thus indicating that these binding sites are presumably involved in the blockade of ACh release by neurotoxic PLA2s. Images Figure 8 Figure 9 PMID:8583413

  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. 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. PMID:26501503

  1. 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.

  2. 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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 40 CFR Appendix A to Part 75 - Specifications and Test Procedures

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... require) performing a flow profile study following the procedures in 40 CFR part 60, appendix A, method, 1... 40 CFR part 60, appendix A, Test Method 1, section 11.5 may be used even if the flow measurement... Spectrometry, for sulfur content of solid or liquid fuels; ASTM D3176-89 (Reapproved 2002), Standard...

  8. 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...

  9. 50 CFR 648.90 - NE multispecies assessment, framework procedures and specifications, and flexible area action...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... as defined under 50 CFR 600.10, in accordance with the procedures specified in § 648.55 (d) and (e... to, changes in the target fishing mortality rates, minimum biomass thresholds, numerical estimates of parameter values, and the use of a proxy for biomass may be made either through a biennial adjustment...

  10. 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... 40 CFR part 60, appendix A, Test Method 1, section 11.5 may be used even if the flow measurement... sulfur content and minimum GCV shall be determined from all available fuel sampling and analysis data...

  11. 40 CFR Appendix A to Part 75 - Specifications and Test Procedures

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... require) performing a flow profile study following the procedures in 40 CFR part 60, appendix A, method, 1... 40 CFR part 60, appendix A, Test Method 1, section 11.5 may be used even if the flow measurement... following: (1) The AETB's quality manual. For the purpose of application of 40 CFR part 2, subpart B,...

  12. 40 CFR Appendix A to Part 75 - Specifications and Test Procedures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... require) performing a flow profile study following the procedures in 40 CFR part 60, appendix A, method, 1... 40 CFR part 60, appendix A, Test Method 1, section 11.5 may be used even if the flow measurement... following: (1) The AETB's quality manual. For the purpose of application of 40 CFR part 2, subpart B,...

  13. 40 CFR Appendix A to Part 75 - Specifications and Test Procedures

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... require) performing a flow profile study following the procedures in 40 CFR part 60, appendix A, method, 1... 40 CFR part 60, appendix A, Test Method 1, section 11.5 may be used even if the flow measurement... following: (1) The AETB's quality manual. For the purpose of application of 40 CFR part 2, subpart B,...

  14. Welding procedure specification: gas tungsten arc welding of AISI 41XX steels

    SciTech Connect

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

    1985-08-01

    Procedure WPS-126 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of AISI 4130 and 4142 steel (ASTM A519) (P-No: None), 0.438-in. wall pipe; filler metal is AMS 6457, Class 4130 MC (F-, A-No: None).

  15. 50 CFR 648.90 - NE multispecies assessment, framework procedures and specifications, and flexible area action...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 CFR 600.10, in accordance with the procedures specified in § 648.55 (d) and (e). (3) Council...; 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...

  16. 50 CFR 648.90 - NE multispecies assessment, framework procedures and specifications, and flexible area action...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... as defined under 50 CFR 600.10, in accordance with the procedures specified in § 648.55 (d) and (e...; 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...

  17. 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

    2015-11-01

    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 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

  19. 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. PMID:26329035

  20. 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.

  1. 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

  2. A comparison of opioid use between WCB recipients and other Manitobans for knee, shoulder, back and carpal tunnel release procedures

    PubMed Central

    Raymond, Colette B.; Ekuma, Okechukwu; Shafer, Leigh Anne

    2016-01-01

    Background This study's objectives were to evaluate whether WCB claimants with conditions requiring certain surgical procedures are more likely to be prescribed outpatient opioids than other Manitobans and whether those prescribed opioids are more likely to still be on opioid medications 6 months post procedure. Methods We compared 7,246 WCB claims for a number of surgical procedures to 65,032 similar procedures performed in other Manitobans. Logistic regression was used to explore the association between being a WCB claimant and being prescribed opioids, while controlling for type of surgical procedure and other potential confounders. Results WCB claimants were more likely than other Manitobans to be prescribed opioids (adjusted OR 1.38; 95%CI 1.30–1.47). Amongst those prescribed opioids, the odds of being still on opioids 6 months post‐procedure were not significantly elevated for WCB claimants (adjusted OR 1.09 95%CI 0.97–1.23). Conclusions WCB claimants are prescribed opioids more often than non‐claimants for similar procedures. Am. J. Ind. Med. 59:257–263, 2016. © 2016 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:26792402

  3. 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.

  4. 14 CFR 151.27 - Procedures: Application, plans, specifications, and appraisals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... layout plan approved by the Administrator; and (2) Preliminary plans and specifications in enough detail... accomplishing the project in accordance with the master plan layout, the rules in subparts B and C...

  5. 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.

  6. Patient-Specific Surgical Planning, Where Do We Stand? The Example of the Fontan Procedure.

    PubMed

    de Zélicourt, Diane A; Kurtcuoglu, Vartan

    2016-01-01

    The Fontan surgery for single ventricle heart defects is a typical example of a clinical intervention in which patient-specific computational modeling can improve patient outcome: with the functional heterogeneity of the presenting patients, which precludes generic solutions, and the clear influence of the surgically-created Fontan connection on hemodynamics, it is acknowledged that individualized computational optimization of the post-operative hemodynamics can be of clinical value. A large body of literature has thus emerged seeking to provide clinically relevant answers and innovative solutions, with an increasing emphasis on patient-specific approaches. In this review we discuss the benefits and challenges of patient-specific simulations for the Fontan surgery, reviewing state of the art solutions and avenues for future development. We first discuss the clinical impact of patient-specific simulations, notably how they have contributed to our understanding of the link between Fontan hemodynamics and patient outcome. This is followed by a survey of methodologies for capturing patient-specific hemodynamics, with an emphasis on the challenges of defining patient-specific boundary conditions and their extension for prediction of post-operative outcome. We conclude with insights into potential future directions, noting that one of the most pressing issues might be the validation of the predictive capabilities of the developed framework. PMID:26183962

  7. 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

  8. 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. PMID:25174374

  9. 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.

  10. 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.

  11. Lipid oxidation in trout muscle is strongly inhibited by a protein that specifically binds hemin released from hemoglobin

    PubMed Central

    Cai, He; Grunwald, Eric W; Park, Sungyong; Lei, Benfang; Richards, Mark P.

    2013-01-01

    The recombinant Streptococcal protein apoShp can be used as a probe for hemoglobin (Hb) reactivity in fish muscle due to its specific affinity for hemin that is released from Hb at post mortem pH values. Hemin affinity measurements indicated that apoShp binds hemin released from Hb but not myoglobin (Mb). Hemin affinity of holoShp was higher at pH 5.7 compared to pH 8.0. This may be attributed to enhanced electrostatic interaction of His58 with the heme-7-propionate at lower pH. ApoShp readily acquired hemin that was released from trout IV metHb in the presence of washed cod muscle during 2°C storage at pH 6.3. This was based on increases in redness in the washed cod matrix which occurs when apoShp binds hemin that is released from metHb. ApoShp prevented Hb-mediated lipid oxidation in washed cod muscle during 2°C storage. The prevention of Hb-mediated lipid oxidation by apoShp was likely due to bis-methionyl coordination of hemin that dissociated from metHb. This hexa-coordination of hemin appears to prevent peroxide-mediated redox reactions and there is no component in the matrix capable of dissociating hemin from Shp. ApoShp was also added to minced muscle from Rainbow trout (Oncorhynchus mykiss) to examine the degree to which Hb contributes to lipid oxidation in trout muscle. Addition of apoShp inhibited approximately 90% of the lipid oxidation that occurred in minced trout muscle during 9 days of 2°C storage based on lipid peroxide, hexanal, and thiobarituric acid reactive substances (TBARS) values. These results strongly suggest that Hb is the primary promoter of lipid oxidation in trout muscle. PMID:23570608

  12. [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. PMID:16422505

  13. [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.

  14. 24 CFR 200.942 - 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 carpet and carpet with attached... for carpet and carpet with attached cushion. (a) Applicable standards. (1) Carpet and carpet with... 1983)—Standard Specification for Rubber Cellular Cushion Used for Carpet or Rug Underlay; (vii)...

  15. 24 CFR 200.942 - 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 carpet and carpet with attached... for carpet and carpet with attached cushion. (a) Applicable standards. (1) Carpet and carpet with... 1983)—Standard Specification for Rubber Cellular Cushion Used for Carpet or Rug Underlay; (vii)...

  16. 24 CFR 200.942 - 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 carpet and carpet with attached... for carpet and carpet with attached cushion. (a) Applicable standards. (1) Carpet and carpet with... 1983)—Standard Specification for Rubber Cellular Cushion Used for Carpet or Rug Underlay; (vii)...

  17. 24 CFR 200.942 - 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 carpet and carpet with attached... for carpet and carpet with attached cushion. (a) Applicable standards. (1) Carpet and carpet with... 1983)—Standard Specification for Rubber Cellular Cushion Used for Carpet or Rug Underlay; (vii)...

  18. 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).

  19. Monitoring of kidney and simultaneous pancreas-kidney transplantation rejection by release of donor-specific, soluble HLA class I.

    PubMed

    DeVito-Haynes, L D; Jankowska-Gan, E; Sollinger, H W; Knechtle, S J; Burlingham, W J

    1994-07-01

    Using an HLA-A2-specific ELISA we monitored daily pretransplantation and posttransplantation sera from five kidney and eight simultaneous pancreas-kidney HLA-A2-negative recipients of HLA-A2-positive transplants during hospitalization. We found that, unlike liver transplants, neither kidney nor simultaneous pancreas-kidney transplants continuously secreted donor HLA proteins. However, three of four rejection episodes in kidney recipients and seven of seven rejection episodes in simultaneous pancreas-kidney recipients were accompanied by elevated serum levels of donor sHLA-A2 (> 5 ng/ml). In only one kidney patient was there a release of donor antigen without evidence of rejection, but in the simultaneous pancreas-kidney group most patients had at least one time point of detectable sHLA-A2 without strong evidence of kidney rejection. While total sHLA levels were also elevated during rejection, the rise in donor-specific sHLA was more dramatic when compared to pretransplantation background levels. We hypothesized that the release of donor sHLA class I proteins by transplanted organs might be a systemic indication of rejection in both pancreas and kidney allografts. The detection of donor sHLA in recipient sera could be an important noninvasive monitor of rejection, especially in the pancreas, which is currently difficult to monitor as a single-organ transplant. PMID:7960963

  20. 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. PMID:24684664

  1. 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.

  2. Radioactive particulate release associated with the DOT specification 6M container under hypothetical accident conditions

    SciTech Connect

    Taylor, J.M.; Raney, P.J.

    1986-02-01

    A testing program was conducted to determine the leakage of depleted uranium dioxide powder (DUO) from the inner containment components of the US Department of Transportation's (DOT) specification 6M container under hypothetical accident conditions. Depleted uranium dioxide was selected as a surrogate for plutonium oxide because of the similarities in the powder characteristics, density and particle size, and because of the special handling and special facilities required for plutonium oxide. The DUO was packaged inside food pack cans in three different configurations inside the 2R vessel of the 6M container. The amount of DUO powder leakage ranged from none detectable (<2 x 10/sup -7/ g) to a high of 1 x 10/sup -3/ g. The combination of gravity, vibration and pressure produced the highest leakage of DUO. Containers that had hermetic seals (leak rates <6 x 10/sup -4/ atm cc/min) did not leak any detectable amount (<2 x 10/sup -7/ g) of DUO under the test conditions. Impact forces had no effect on the leakage of particles with the packaging configurations used. 23 refs., 24 figs., 3 tabs.

  3. 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

  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. Production of 191Pt radiotracer with high specific activity for the development of preconcentration procedures

    NASA Astrophysics Data System (ADS)

    Parent, M.; Strijckmans, K.; Cornelis, R.; Dewaele, J.; Dams, R.

    1994-04-01

    A radiotracer of Pt with suitable nuclear characteristics and high specific activity (i.e. activity to mass ratio) is a powerful tool when developing preconcentration methods for the determination of base-line levels of Pt in e.g. environmental and biological samples. Two methods were developed for the production of 191Pt with high specific activity and radionuclidic purity: (1) via the 190Pt(n, γ) 191Pt reaction by neutron irradiation of enriched Pt in a nuclear reactor at high neutron fluence rate and (2) via the 191Ir(p, n) 191Pt reaction by proton irradiation of natural Ir with a cyclotron, at an experimentally optimized proton energy. For the latter method it was necessary to separate Pt from the Ir matrix. For that reason either liquid-liquid extraction with dithizone or adsorption chromatography were used. The yields, the specific activities and the radionuclidic purities were experimentally determined as a function of the proton energy and compared to the former method. The half-life of 191Pt was accurately determined to be 2.802 ± 0.025 d.

  6. Co-stimulation-induced release of pro-inflammatory cytokine interleukin-8 by allergen-specific T cells.

    PubMed

    Spinozzi, F; Agea, E; Piattoni, S; Bistoni, O; Grignani, F; Bertotto, A

    1996-07-01

    Chemokines, which include interleukin (IL)-8, are a family of pro-inflammatory molecules with potent chemoattractant activity on neutrophils, as well as other cell types. IL-8 can be recovered from many inflammatory sites. To test the hypothesis that Th2-type allergen-specific T cells, known to be the main cell type governing the allergic inflammation, are a source of IL-8 and to investigate whether IL-8 release is influenced by the nature of the in vitro mitogenic or co-mitogenic stimulation, cypress-specific T-cell clones (TCC) were generated from five allergic subjects during in vitro seasonal exposure to the allergen. Purified cypress extract was produced directly from freshly collected pollen and used for in vitro stimulation of PBMC bulk cultures. After 5 days priming and a further 7 day period of IL-2-driven cell expansion, monoclonal antibodies to CD3, CD2 and CD28 were adopted for in vitro restimulation of allergen-specific cell lines or, subsequently, secondary established TCC. The induction of apoptosis was detected by propidium iodide (PI) cytofluorimetric assay. Basal and co-stimulation-induced IL-8 production was measured by an ELISA method. Both cypress-specific T-cell lines and TCC secreted appreciable amounts of IL-8. By cross-linking T-cell lines or Th2 CD4+ TCC with CD3, CD2 or CD28 MoAbs, the authors observed a great stimulation-induced IL-8 secretion, preferentially after CD2 or combined CD2/CD28 stimulation. In addition, CD4+ clones released large amounts of IL-8 into culture supernatants after CD2 stimulation while undergoing programmed cell death (30-40% hypodiploid DNA profile of PI-stained cells). In contrast, CD3 crosslinking was unable to determine the release of IL-8 or the induction of apoptosis. Taken together, these results suggest that incomplete TcR engagement by allergen may lead to the secretion of pro-inflammatory cytokines with a contemporary induction of apoptosis in a significant number of target cells. This phenomenon may

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

    PubMed Central

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

    2014-01-01

    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). PMID:24334296

  8. 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).

  9. A novel three-color, clone-specific fluorescence in situ hybridization procedure for monoclonal gammopathies.

    PubMed

    Ahmann, G J; Jalal, S M; Juneau, A L; Christensen, E R; Hanson, C A; Dewald, G W; Greipp, P R

    1998-02-01

    We have developed a three-color cytoplasmic immunoglobulin (cIg) and fluorescence in situ hybridization (FISH) technique to detect plasma cell chromosomal aneuploidy in patients with multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and amyloidosis (AL). Immunofluorescent-labeled antibodies to detect light chain expression and six directly labeled alpha-satellite chromosome specific enumeration probes (CEP) were used simultaneously to detect aneuploidy of the plasma cells. The six probes were specific for chromosomes 7, 9, 11, 15, 18, and X. The technique was tested in 12 consecutive patient samples (5 MM, 2 MGUS, 3 SMM, and 2 AL). Based on the alpha-satellite signals, we found trisomic clones for CEP 7 (4 of 12), CEP 11 (4 of 12), CEP X (1 of 12), CEP 9 (8 of 12), CEP 15 (7 of 12), and CEP 18 (5 of 12). Trisomic clones of at least one of the six chromosomes were present in 9 of 12 patients. We believe that this technique efficiently identifies monotypic plasma cells and permits simultaneous analysis of numeric chromosome anomalies by FISH in emerging neoplastic cells. We are in the process of applying this technique to a series of about 100 newly diagnosed monoclonal gammopathy patients. PMID:9460493

  10. Chronic Stress Induces Sex-Specific Alterations in Methylation and Expression of Corticotropin-Releasing Factor Gene in the Rat

    PubMed Central

    Sterrenburg, Linda; Gaszner, Balázs; Boerrigter, Jeroen; Santbergen, Lennart; Bramini, Mattia; Elliott, Evan; Chen, Alon; Peeters, Bernard W. M. M.; Roubos, Eric W.; Kozicz, Tamás

    2011-01-01

    Background Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive. Methods Male and female rats were exposed to chronic variable mild stress (CVMS) after which immediate early gene products, corticotropin-releasing factor (CRF) mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN), oval (BSTov) and fusiform (BSTfu) parts of the bed nucleus of the stria terminalis, and central amygdala (CeA). Results CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females. Conclusions The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression. PMID:22132228

  11. 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

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25714031

  13. Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility.

    PubMed

    Nelson, Benjamin R; Wu, Fenfen; Liu, Yun; Anderson, Douglas M; McAnally, John; Lin, Weichun; Cannon, Stephen C; Bassel-Duby, Rhonda; Olson, Eric N

    2013-07-16

    Excitation-contraction (EC) coupling comprises events in muscle that convert electrical signals to Ca(2+) transients, which then trigger contraction of the sarcomere. Defects in these processes cause a spectrum of muscle diseases. We report that STAC3, a skeletal muscle-specific protein that localizes to T tubules, is essential for coupling membrane depolarization to Ca(2+) release from the sarcoplasmic reticulum (SR). Consequently, homozygous deletion of src homology 3 and cysteine rich domain 3 (Stac3) in mice results in complete paralysis and perinatal lethality with a range of musculoskeletal defects that reflect a blockade of EC coupling. Muscle contractility and Ca(2+) release from the SR of cultured myotubes from Stac3 mutant mice could be restored by application of 4-chloro-m-cresol, a ryanodine receptor agonist, indicating that the sarcomeres, SR Ca(2+) store, and ryanodine receptors are functional in Stac3 mutant skeletal muscle. These findings reveal a previously uncharacterized, but required, component of the EC coupling machinery of skeletal muscle and introduce a candidate for consideration in myopathic disorders. PMID:23818578

  14. Convergence and constraint in eukaryotic release factor 1 (eRF1) domain 1: the evolution of stop codon specificity

    PubMed Central

    Inagaki, Yuji; Blouin, Christian; Doolittle, W. Ford; Roger, Andrew J.

    2002-01-01

    Class 1 release factor in eukaryotes (eRF1) recognizes stop codons and promotes peptide release from the ribosome. The ‘molecular mimicry’ hypothesis suggests that domain 1 of eRF1 is analogous to the tRNA anticodon stem–loop. Recent studies strongly support this hypothesis and several models for specific interactions between stop codons and residues in domain 1 have been proposed. In this study we have sequenced and identified novel eRF1 sequences across a wide diversity of eukaryotes and re-evaluated the codon-binding site by bioinformatic analyses of a large eRF1 dataset. Analyses of the eRF1 structure combined with estimates of evolutionary rates at amino acid sites allow us to define the residues that are under structural (i.e. those involved in intramolecular interactions) versus non-structural selective constraints. Furthermore, we have re-assessed convergent substitutions in the ciliate variant code eRF1s using maximum likelihood-based phylogenetic approaches. Our results favor the model proposed by Bertram et al. that stop codons bind to three ‘cavities’ on the protein surface, although we suggest that the stop codon may bind in the opposite orientation to the original model. We assess the feasibility of this alternative binding orientation with a triplet stop codon and the eRF1 domain 1 structures using molecular modeling techniques. PMID:11788716

  15. Determining organisation-specific factors for developing health interventions in companies by a Delphi procedure: Organisational Mapping.

    PubMed

    van Scheppingen, Arjella R; ten Have, Kristin C J M; Zwetsloot, Gerard J I M; Kok, Gerjo; van Mechelen, Willem

    2015-12-01

    Companies, seen as social communities, are major health promotion contexts. However, health promotion in the work setting is often less successful than intended. An optimal adjustment to the organisational context is required. Knowledge of which organisation-specific factors are relevant to health promotion is scarce. A Delphi procedure is used to identify these factors. The aim is to contribute to more effective workplace health promotion. The identified factors are described and embedded into a practical methodology (Intervention Mapping). A systematic use of these factors (called 'Organisational Mapping') is likely to contribute to more effective health promotion in the work setting.

  16. Determining organisation-specific factors for developing health interventions in companies by a Delphi procedure: Organisational Mapping.

    PubMed

    van Scheppingen, Arjella R; ten Have, Kristin C J M; Zwetsloot, Gerard J I M; Kok, Gerjo; van Mechelen, Willem

    2015-12-01

    Companies, seen as social communities, are major health promotion contexts. However, health promotion in the work setting is often less successful than intended. An optimal adjustment to the organisational context is required. Knowledge of which organisation-specific factors are relevant to health promotion is scarce. A Delphi procedure is used to identify these factors. The aim is to contribute to more effective workplace health promotion. The identified factors are described and embedded into a practical methodology (Intervention Mapping). A systematic use of these factors (called 'Organisational Mapping') is likely to contribute to more effective health promotion in the work setting. PMID:26573181

  17. 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

  18. 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.

  19. Construction of a human chromosome 3 specific NotI linking library using a novel cloning procedure.

    PubMed Central

    Zabarovsky, E R; Boldog, F; Thompson, T; Scanlon, D; Winberg, G; Marcsek, Z; Erlandsson, R; Stanbridge, E J; Klein, G; Sümegi, J

    1990-01-01

    Two new diphasmid vectors (lambda SK17 and SK22) and a novel procedure to construct linking libraries are described. A partial filling-in reaction provides counter-selection against false linking clones in the library, and obviates the need for supF selection. The diphasmid vectors, in combination with the novel selection procedure, have been used to construct a chromosome 3 specific NotI linking library from a human chromosome 3/mouse microcell hybrid cell line. The application of the new vectors and the strong biochemical and biological selections resulted in a library of 60,000 NotI linking clones. As practically all of them are real NotI linking clones (no false recombinants) the library represents approximately 3,000 human recombinants (equal to 10-15 genomic equivalents of chromosome 3). Previously published methods for construction of linking libraries are compared with the procedure described in the present paper. The advantages of the new vectors and the novel protocol are discussed. Images PMID:2243778

  20. A Rapid, Specific Membrane Filtration Procedure for Enumeration of Enterococci in Recreational Water

    PubMed Central

    Messer, James W.; Dufour, Alfred P.

    1998-01-01

    A two-step membrane filter (MF) method with mE medium, upon which the membrane must be incubated for 48 h and then transferred to a substrate medium to differentiate enterococci, is recommended by the U.S. Environmental Protection Agency to measure enterococci in fresh and marine recreational waters. The original mE medium was modified by reducing the triphenyltetrazolium chloride from 0.15 to 0.02 g/liter and adding 0.75 g of indoxyl β-d-glucoside per liter. The new MF medium, mEI medium, detected levels of enterococci in 24 h comparable to those detected by the original mE medium in 48 h, with the same level of statistical confidence. In addition, the use of mEI medium eliminated the need to transfer the membrane to a substrate medium to differentiate enterococci from other genera of the fecal streptococcal group. Colonies from mEI medium were examined to determine the rates of false-positive and false-negative occurrences. mEI medium had a false-positive rate of 6.0% and a false-negative rate of 6.5%. Interlaboratory testing of the MF method with mEI medium demonstrated that the relative reproducibility standard deviations among laboratories ranged from 2.2% for marine water to 18.9% for freshwater. The comparative recovery studies, specificity determinations, and multilaboratory evaluation indicated that mEI medium has analytical performance characteristics equivalent to those of mE medium. The simplicity of use and decreased incubation time with mEI medium will facilitate the detection and quantification of enterococci in fresh and marine recreational waters. PMID:9464407

  1. 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)

  2. 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.

  3. Cell type-specific roles for tissue plasminogen activator released by neurons or microglia after excitotoxic injury.

    PubMed

    Siao, Chia-Jen; Fernandez, Susana R; Tsirka, Stella E

    2003-04-15

    Tissue plasminogen activator (tPA) plays important roles in the brain after excitotoxic injury. It is released by both neurons and microglia and mediates neuronal death and microglial activation. Mice lacking tPA are resistant to excitotoxicity and show very limited microglial activation. Activated microglia are neurotoxic in culture, but this phenomenon is not well documented in vivo. To further understand the sequence of events through which tPA mediates microglial activation and neurodegeneration, we have generated mice that exhibit restricted expression of tPA through introduction of tPA transgenes under the control of neuronal- or microglial-specific promoters into tPA-deficient mice. Neither strain of transgenic mice shows abnormal brain morphology or inflammation in the absence of injury, and unilateral intrahippocampal kainate injections into the transgenic mice induced excitotoxicity and microglial activation reminiscent of wild-type mice. However, there are differences in the kinetics of the resulting pathology. The neuronal tPA-expressing mice exhibit accelerated microglial activation compared with wild-type or microglial tPA-expressing mice. However, microglial tPA-expressing mice exhibit greater neurodegeneration. These data suggest a model in which tPA plays different roles after kainate injection depending on whether it is released by neurons or microglia. We propose that tPA, initially secreted from injured neurons, acts as a cytokine to activate microglia at the site of injury. These activated microglia then secrete additional tPA, which promotes extracellular matrix degradation, neurodegeneration, and self-proliferation. We suggest that an approach to attenuate microglia-mediated neuronal death in vivo might be to pharmacologically prevent microglial activation.

  4. Molecular cloning and tissue-specific expression of a gonadotropin-releasing hormone receptor in the Japanese eel.

    PubMed

    Okubo, K; Suetake, H; Usami, T; Aida, K

    2000-08-01

    Gonadotropin-releasing hormone (GnRH) is a key regulatory neuropeptide involved in the control of reproduction in vertebrates. In the Japanese eel, one of the most primitive teleost species, two molecular forms of GnRH, mammalian-type GnRH and chicken-II-type GnRH (cGnRH-II), have been identified. This study has isolated a full-length cDNA for a GnRH receptor from the pituitary of the eel. The 3233-bp cDNA encodes a 380-amino acid protein which contains seven hydrophobic transmembrane domains and N- and C-terminal regions. The exon/intron organization of the open reading frame of the eel GnRH receptor gene was also determined. The open reading frame consists of three exons and two introns. The exon-intron splice site is similar to that of the GnRH receptor genes of mammals reported so far. Expression of the eel GnRH receptor was detected in various parts of the brain, pituitary, eye, olfactory epithelium, and testis. This result suggests that GnRH has local functions in these tissues in addition to its actions on gonadotropin synthesis and release in the pituitary. This tissue-specific expression pattern is similar to that of the eel cGnRH-II. Furthermore, the present eel receptor shows very high amino acid identity with the catfish and goldfish GnRH receptors, which are highly selective for the cGnRH-II. These results suggest that the cGnRH-II acts through binding to the present receptor in the eel.

  5. Optimization Correction Strength Using Contra Bending Technique without Anterior Release Procedure to Achieve Maximum Correction on Severe Adult Idiopathic Scoliosis

    PubMed Central

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Purnaning, Dyah; Kurniawati, Tri

    2016-01-01

    Adult scoliosis is defined as a spinal deformity in a skeletally mature patient with a Cobb angle of more than 10 degrees in the coronal plain. Posterior-only approach with rod and screw corrective manipulation to add strength of contra bending manipulation has correction achievement similar to that obtained by conventional combined anterior release and posterior approach. It also avoids the complications related to the thoracic approach. We reported a case of 25-year-old male adult idiopathic scoliosis with double curve. It consists of main thoracic curve of 150 degrees and lumbar curve of 89 degrees. His curve underwent direct contra bending posterior approach using rod and screw corrective manipulation technique to achieve optimal correction. After surgery the main thoracic Cobb angle becomes 83 degrees and lumbar Cobb angle becomes 40 degrees, with 5 days length of stay and less than 800 mL blood loss during surgery. There is no complaint at two months after surgery; he has already come back to normal activity with good functional activity. PMID:27064801

  6. 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

  7. 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.

  8. 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.

  9. Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis

    PubMed Central

    Kumar, Rajiv; Singh, Neetu; Gautam, Shalini; Singh, Om Prakash; Gidwani, Kamlesh; Rai, Madhukar; Sacks, David

    2014-01-01

    Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs) typically fail to respond to stimulation with leishmanial antigen. Unexpectedly, it was recently shown that Leishmania specific IFNγ, can readily be detected when a whole blood stimulation assay (WBA) is used. We sought to define the conditions that permit whole blood cells to respond to antigen stimulation, and clarify the biological role of the IFNγ found to be released by cells from VL patients. CD4+ T cells were found to be crucial for and the main source of the IFNγ production in Leishmania stimulated whole blood (WB) cultures. Complement, antibodies and red blood cells present in whole blood do not play a significant role in the IFNγ response. The IFNγ production was reduced by blockade of human leukocyte antigen (HLA)-DR, indicating that the response to leishmanial antigens observed in WB of active VL patients is a classical HLA- T cell receptor (TCR) driven reaction. Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth. PMID:25275531

  10. Tumor Specific Epigenetic Silencing of Corticotropin Releasing Hormone -Binding Protein in Renal Cell Carcinoma: Association of Hypermethylation and Metastasis

    PubMed Central

    Tezval, Hossein; Dubrowinskaja, Natalia; Peters, Inga; Reese, Christel; Serth, Katrin; Atschekzei, Faranaz; Hennenlotter, Jörg; Stenzl, Arnulf; Kuczyk, Markus A.; Serth, Jürgen

    2016-01-01

    The relevance of Corticotropin Releasing Hormone (CRH)-system in human malignancies is a question of growing interest. Here we investigated hypermethylation and epigenetic silencing of the CRH-Binding Protein (CRHBP) gene in clear cell renal cell cancer (ccRCC). Relative methylation of the CRHBP CpG island (CGI) was determined in 17 tumor cell lines as well as 86 ccRCC samples and 66 paired normal tissues using pyrosequencing and quantitative methylation specific PCR of bisulfite converted DNA. Results were statistically compared with relative mRNA expression levels of CRHBP and clinicopathological parameters of patients. Re-expression of CRHBP following 5-aza-2´-deoxycytidine treatment was investigated by quantitative mRNA expression analysis. Real-time impedance analysis was applied for analysis of invasiveness of renal tumor cells following si-RNA knockdown of CRHBP expression or ectopic expression of CRHBP. We found the CRHBP CGI to be frequently methylated in tumor cell lines of renal, prostatic, and bladder cancer. Comparison of methylation in normal and paired renal cancer tissue specimens revealed hypermethylation of the CRHBP CGI in tumors (p<1*10−12). DNA methylation and decreased mRNA expression were correlated (R = 0.83, p<1*10−12). Tumor cell lines showed 5-aza-2´-deoxycytidine dependent reduction of methylation and re-expression of CRHBP was associated with altered cellular invasiveness of renal cancer cells in real-time impedance invasion assays. Hypermethylation and inverse relationship with mRNA expression were validated in silico using the TCGA network data. We describe for the first time tumor specific epigenetic silencing of CRHBP and statistical association with aggressive tumors thus suggesting the CRH system to contribute to the development of kidney cancer. PMID:27695045

  11. 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. PMID:24805264

  12. 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.

  13. Comprehensive Data Scientific Procedure for Enhanced Analysis and Interpretation of Real-Time Breath Measurements in In Vivo Aroma-Release Studies.

    PubMed

    Szymańska, Ewa; Brown, Phil A; Ziere, Aldo; Martins, Sara; Batenburg, Max; Harren, Frans J M; Buydens, Lutgarde M C

    2015-10-20

    Real-time measurements of many low-abundance volatile organic compounds (VOCs) in breath and air samples are already feasible due to progress in analytical technologies, such as proton transfer reaction mass spectrometry (PTR-MS). Nevertheless, the information content of real-time measurements is not fully exploited, due to the lack of suitable data handling methods. This study develops a data scientific procedure to enhance data analysis and interpretation of longitudinal, multivariate data sets from real-time, in vivo, aroma-release studies. The developed procedure includes an automated data preprocessing and a multivariate assessment of the test panel performance. A large multifactorial PTR-MS data set is investigated that includes four experimental protocols, two tested food products, four aroma compounds, and eight panelists. Real-time measurements are converted into standardized breath profiles by preprocessing, and 10 kinetic parameters are derived. Next to this, panel performance is evaluated per experimental protocol and food product. Comprehensive information about panel performance, individual panelists, studied products, aroma compounds, and kinetic parameters is extracted, demonstrating the great value of the developed approach.

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

    SciTech Connect

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

    1986-06-01

    Procedure WPS-126 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of AISI 4130 and 4142 steel (ASTM A519) (P-No: None), 0.438-inch wall pipe; filler metal is AMS 6457, Class 4130 MC (F-, A-No: None).

  15. 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.

  16. 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. PMID:23849308

  17. Photocontrol of NO, H2S, and HNO Release in Biological Systems by Using Specific Caged Compounds.

    PubMed

    Nakagawa, Hidehiko

    2016-01-01

    Nitric oxide (NO) is a gas that plays various roles in physiological signal transduction, for example, in vasodilation, neural transmission, and biodefence. Recently, other gaseous signal mediators such as carbon monoxide (CO) and hydrogen sulfide (H2S) have also been found to have important biological activities. Since experimental studies with gaseous mediators are difficult, chemicals that enable controlled release of these gases are indispensable. We have developed a range of photocontrollable releasers that generate NO, H2S, and related species with fine spatiotemporal control, and we have also employed these caged compounds in various applications. This paper briefly reviews our work on photocontrollable NO, H2S, and HNO releasers, and presents some typical applications illustrating the suitability of our compounds for controlled release of these biologically active species in cellular and tissue systems. These compounds also appear to have potential for future therapeutic applications. PMID:27581628

  18. A correlation between the ligand specificity for 67copper uptake and for copper-prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from median eminence explants.

    PubMed

    Barnea, A; Cho, G; Hartter, D E

    1988-04-01

    We have previously shown that copper (Cu) leads to a 3- to 4-fold amplification of prostaglandin E2 (PGE2) stimulation of LHRH release from explants of the median eminence area (MEA), that this amplification is a saturable function of [Cu], and that complexed Cu but not ionic Cu is the active form of the metal. This implicates a ligand-specific site in Cu action. In this study we address the following questions. Is there a ligand specificity for Cu amplification of PGE2 stimulation of LHRH release, and if so, does it correlate with the ligand specificity for Cu uptake? MEAs of 1-month-old female rats were incubated for 5 min with 150 microM Cu solution and then for 15 min with 10 microM PGE2 (Cu/PGE2); LHRH released into the medium was evaluated by RIA. To assess Cu uptake, MEAs were incubated with 100 microM67 Cu solution for 15 min, and 67Cu accumulation by the MEA was evaluated. The Cu was complexed to one of the following ligands: histamine, His, Cys, Thr, Gly, glutathione, Gly-His-Lys, or albumin. There was a high degree of correlation (r = 0.943) between the ligand specificity for Cu/PGE2 stimulation of LHRH release (Cu action) and 67Cu uptake. Complexation of ionic Cu with His facilitated Cu action and 67Cu uptake 3-fold each, and this was completely prevented by the inclusion of His in a 100-fold excess over the concentration of the Cu/His complex. Histamine, the amino acids, and the peptides facilitated Cu action and 67Cu uptake, whereas albumin did not do so. Of these facilitatory ligands, histamine and His were the most effective and Gly-His-Lys was the least effective. In summary, both 67Cu uptake and Cu action are ligand-dependent and ligand-specific; the Cu interactive sites have a common recognition for the Cu-ligand complex and for the ligand itself; and the ligand specificity for 67Cu uptake and for Cu action are highly correlated. These results are consistent with the ligand specificity for Cu uptake being the primary determinant of the ligand

  19. 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.

  20. Visible Light-Controlled Nitric Oxide Release from Hindered Nitrobenzene Derivatives for Specific Modulation of Mitochondrial Dynamics.

    PubMed

    Kitamura, Kai; Kawaguchi, Mitsuyasu; Ieda, Naoya; Miyata, Naoki; Nakagawa, Hidehiko

    2016-05-20

    Nitric oxide (NO) is a physiological signaling molecule, whose biological production is precisely regulated at the subcellular level. Here, we describe the design, synthesis, and evaluation of novel mitochondria-targeted NO releasers, Rol-DNB-mor and Rol-DNB-pyr, that are photocontrollable not only in the UV wavelength range but also in the biologically favorable visible wavelength range (530-590 nm). These caged NO compounds consist of a hindered nitrobenzene as the NO-releasing moiety and a rhodamine chromophore. Their NO-release properties were characterized by an electron spin resonance (ESR) spin trapping method and fluorometric analysis using NO probes, and their mitochondrial localization in live cells was confirmed by costaining. Furthermore, we demonstrated visible light control of mitochondrial fragmentation via activation of dynamin-related protein 1 (Drp1) by means of precisely controlled NO delivery into mitochondria of cultured HEK293 cells, utilizing Rol-DNB-pyr. PMID:26878937

  1. 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

  2. Increasing level of prostate-specific antigen and prostate cancer risk factors among 193 men examined in screening procedure.

    PubMed

    Opalińska, Edyta; Michalak, Anna; Stoma, Filip; Latalski, Maciej; Goniewicz, Mariusz

    2003-01-01

    Prostate cancer is one of the most common cancers in men, therefore has become recently an essential problem of public health. The factors influencing cancer include: androgens metabolism disorders, diabetes mellitus, overweight and obesity, smoking, alcohol and black coffee intake, diet rich in saturated fats and poor in unsaturated, lack of physical activity, geographical zone, race, such carcinogenic substances as: cadmium, materials used in rubber, painting, printing, ship industry etc., contagious factors and also older age and a positive family history of the disease. To diagnose prostate cancer in its early stage such screening procedures as physical examination--digital rectal exam (DRE) and determination of prostate-specific antigen (PSA) level in blood serum are used. The aim of the study was to assess prostate cancer risk factors occurrence in the examined 193 men, aged 50-70 years, who reported to urology outpatient department at Clinical Hospital in Lublin, measure the PSA level in blood serum and examine the correlation between them. Respondents filled in a questionnaire about the presence of prostate cancer risk factors and urogenital symptoms. The questionnaire was completed with DRE and PSA measurement. The results led us to the following conclusions: 1/ in the studied population elevated PSA level is determined in 3.1% of 193 examined men, 2/ increased PSA occurs mainly in men from rural areas, with elementary education, divorced, older (>60 years), using fat-rich diet, smokers, black coffee drinkers, with overweight or obesity and non diabetic, 3/ a combination of PSA test with DRE seems to be useful and rather cheap for the detection of prostate cancer in the early stage of its development.

  3. 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.

  4. 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

  5. A novel endo-β-N-acetylglucosaminidase releases specific N-glycans depending on different reaction conditions.

    PubMed

    Le Parc, Annabelle; Karav, Sercan; Bell, Juliana Maria Leite Nobrega De Moura; 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 microbiome. 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

  6. 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

  7. Evaluation of the resident-species procedure for developing site-specific water quality criteria for copper in Blaine Creek, Kentucky

    SciTech Connect

    Dobbs, M.G.; Farris, J.L.; Cherry, D.S.; Cairns, J. . Dept. of Biology); Reash, R.J. . Environmental Engineering Div.)

    1994-06-01

    Acute toxicity tests were performed on each of nine different organisms in Blaine Creek (Lawrence County, KY) water to determine 48-h LC50 values for copper (Cu). Blaine Creek is the receiving stream for Kentucky Power Company's Big Sandy Plant fly-ash pond discharge. Selection of the nine tested species and integration of the results were based on the US Environmental Protection Agency's (EPA's) resident-species procedure. The following LC50 ([mu]g Cu/L) values were obtained: Daphnia pulex 37; Physella sp. 109; Isonychia bicolor 223; Pimephales promelas 284; Stenonema sp. 453; Eurycea bislineata 1,120; Chironomus riparius 1,170; Orconectes sp. 2,370; Lepomis macrochirus 4,300. A final acute value (FAV) of 10.1 [mu]g Cu/L was derived using the Blaine Creek database, which is lower than the EPA's national FAV. The differences in FAVs were due to the effect of database size, not differences in the relative sensitivity of test organisms. The findings provide caution for dischargers who may choose to use the resident-species procedure for future site-specific water-quality-criteria demonstrations. The resident-species procedure, because of the inherent conservative bias of the calculation process, tends to produce more stringent criteria when used on a site-specific basis. A modified recalculation procedure, in conduction with site-specific metal bioavailability data, was judged to be the most appropriate method for deriving site-specific Cu criteria for Blaine Creek.

  8. 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…

  9. Polar metabolites synergize the activity of prostaglandin F2α in a species-specific hormonal sex pheromone released by ovulated common carp.

    PubMed

    Lim, Hangkyo; Sorensen, Peter W

    2011-07-01

    Many species of teleost fish detect and release F prostaglandins (PGFs), but the specific identities of these compounds and how they function as species-specific pheromones have yet to be resolved. This study addressed these questions in the common carp. An initial set of experiments established that mature male common carp were attracted to chemicals released by ovulated conspecifics, whereas the odor of female goldfish, a close relative, was less attractive. Tests of fractionated holding water from ovulated carp revealed that only the non-polar fraction was attractive on its own. Mass spectrometry and immunoassay next demonstrated that the non-polar fraction contained large quantities of prostaglandin F(2α) (PGF(2α)), 15keto-prostaglandinF(2α), and 13,14-dihydro-15keto-prostaglandin F(2α) (100 g fish released over 1 μg of all 3 PGFs per h at a ratio of 1.0: 1.7: 0.7). Ovulated goldfish released the same three PGFs but at a slightly greater rate and in a different ratio. Tests of synthetic mixtures of these PGFs revealed that the carp-specific mixture attracted male carp but was no better than the goldfish-specific mixture or PGF(2α) alone and that PGF(2α) was just as attractive as mixture of all three PGFs. A final set of attraction tests revealed that although PGF(2α) could explain all of the activity of the non-polar portion of female carp holding water, it could not explain the entire activity of female water but that a mixture of PGFs and the polar fraction could. We conclude that ovulated female carp release a multi-component sex pheromone complex that is comprised of PGF(2α) and unknown species-specific polar compound(s) that synergize the activity of the former. The pheromone also might be useful in controlling this invasive species. The observation that a fish hormonal sex pheromone incorporates bodily metabolites in addition to relatively common hormonal products demonstrates a mechanism by which species specificity may be conferred to this

  10. 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.

  11. Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex: simultaneous measurement of spontaneous locomotor activity in behaving rats.

    PubMed

    Takase, K; Kimura, F; Yagami, T; Mitsushima, D

    2009-03-01

    The difference in visual object recognition by males and females suggests a sex-specific function in the medial prefrontal cortex (mPFC). In the present study, we performed an in vivo microdialysis study in three groups of rats (males, diestrous females, and proestrous females) to examine the potential sex difference in acetylcholine (ACh) release in the mPFC. The dialysate was automatically collected from the mPFC every 20 min for 24 h under freely moving conditions and the spontaneous locomotor activity was simultaneously monitored. Although ACh release in the mPFC during the dark phase was significantly greater than during the light phase in both sexes, the female rats consistently exhibited a significantly greater mean ACh release than the males. Spontaneous locomotor activity during the dark phase was also significantly greater than during the light phase in both sexes, but the females exhibited significantly greater spontaneous locomotor activity than the males. In addition, both sexes of rats were found to have significant positive correlations between ACh release and spontaneous locomotor activity, but females were found to have significantly greater correlation coefficients than males. Stereological methods were used to examine the number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis and the horizontal diagonal band of Broca. The number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis was also greater in females than males, suggesting a contribution to the higher ACh release in females. In contrast, no sex difference in the choline acetyltransferase immunoreactive cells was observed in the horizontal diagonal band of Broca. This is the first report to show a sex difference in the 24-h ACh release profile in the mPFC of behaving rats.

  12. Sex-specific 24-h acetylcholine release profile in the medial prefrontal cortex: simultaneous measurement of spontaneous locomotor activity in behaving rats.

    PubMed

    Takase, K; Kimura, F; Yagami, T; Mitsushima, D

    2009-03-01

    The difference in visual object recognition by males and females suggests a sex-specific function in the medial prefrontal cortex (mPFC). In the present study, we performed an in vivo microdialysis study in three groups of rats (males, diestrous females, and proestrous females) to examine the potential sex difference in acetylcholine (ACh) release in the mPFC. The dialysate was automatically collected from the mPFC every 20 min for 24 h under freely moving conditions and the spontaneous locomotor activity was simultaneously monitored. Although ACh release in the mPFC during the dark phase was significantly greater than during the light phase in both sexes, the female rats consistently exhibited a significantly greater mean ACh release than the males. Spontaneous locomotor activity during the dark phase was also significantly greater than during the light phase in both sexes, but the females exhibited significantly greater spontaneous locomotor activity than the males. In addition, both sexes of rats were found to have significant positive correlations between ACh release and spontaneous locomotor activity, but females were found to have significantly greater correlation coefficients than males. Stereological methods were used to examine the number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis and the horizontal diagonal band of Broca. The number of choline acetyltransferase immunoreactive cells in the nucleus basalis magnocellularis was also greater in females than males, suggesting a contribution to the higher ACh release in females. In contrast, no sex difference in the choline acetyltransferase immunoreactive cells was observed in the horizontal diagonal band of Broca. This is the first report to show a sex difference in the 24-h ACh release profile in the mPFC of behaving rats. PMID:19162130

  13. Ajoene, the antiplatelet compound derived from garlic, specifically inhibits platelet release reaction by affecting the plasma membrane internal microviscosity.

    PubMed

    Rendu, F; Daveloose, D; Debouzy, J C; Bourdeau, N; Levy-Toledano, S; Jain, M K; Apitz-Castro, R

    1989-04-15

    Ajoene (E,Z-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a product of the rearrangement of allicin (a major component of raw garlic), has been shown to be a potent inhibitor of platelet aggregation in vitro through inhibition of granule release and fibrinogen binding. Our present study further elaborates on this inhibitory action, through studies of the effect of ajoene on the earliest steps of platelet activation. The transducing mechanism involved in thrombin-induced platelet activation was not modified by the drug as indicated by a normal breakdown of phosphatidylinositol 4,5,bisphosphate and normal production of phosphatidic acid. Likewise, the agonist-induced phosphorylation of myosin light chain (P20) and of the 43 kD protein (P43) were not impaired by ajoene. Under the same conditions, however, ajoene (100 microM) produced a strong inhibition of the thrombin-induced release of dense body and alpha-granule constituents. Electron spin resonance studies of the effect of ajoene on some physico-chemical properties of the platelet plasma membrane (intact platelets), as well as on artificial lipid membranes, indicated that ajoene increased mobility of the fatty acid spin label 16 nitroxide stearate. This suggests the existence of a decreased microviscosity of the most internal region within the lipid bilayer membrane, without affecting the outer hydrophilic moieties of the bilayer. As a whole, these results suggest that the effect of ajoene on the release reaction must be, in part, due to physical modification of the bilayer, which impairs the fusion of the granules and plasma membrane, a prerequisite for exocytosis.

  14. Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol.

    PubMed Central

    Harder, T; Kellner, R; Parton, R G; Gruenberg, J

    1997-01-01

    Annexin II is an abundant protein which is present in the cytosol and on the cytoplasmic face of plasma membrane and early endosomes. It is generally believed that this association occurs via Ca(2+)-dependent binding to lipids, a mechanism typical for the annexin protein family. Although previous studies have shown that annexin II is involved in early endosome dynamics and organization, the precise biological role of the protein is unknown. In this study, we found that approximately 50% of the total cellular annexin was associated with membranes in a Ca(2+)-independent manner. This binding was extremely tight, since it resisted high salt and, to some extent, high pH treatments. We found, however, that membrane-associated annexin II could be quantitatively released by low concentrations of the cholesterol-sequestering agents filipin and digitonin. Both treatments released an identical and limited set of proteins but had no effects on other membrane-associated proteins. Among the released proteins, we identified, in addition to annexin II itself, the cortical cytoskeletal proteins alpha-actinin, ezrin and moesin, and membrane-associated actin. Our biochemical and immunological observations indicate that these proteins are part of a complex containing annexin II and that stability of the complex is sensitive to cholesterol sequestering agents. Since annexin II is tightly membrane-associated in a cholesterol-dependent manner, and since it seems to interact physically with elements of the cortical actin cytoskeleton, we propose that the protein serves as interface between membranes containing high amounts of cholesterol and the actin cytoskeleton. Images PMID:9188103

  15. 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

    ... 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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.

  1. Pathogen specific cytokine release reveals an effect of TLR2 Arg753Gln during Candida sepsis in humans.

    PubMed

    Woehrle, Tobias; Du, Weidong; Goetz, Achim; Hsu, Hsin-Yun; Joos, Thomas O; Weiss, Manfred; Bauer, Ute; Brueckner, Uwe B; Marion Schneider, E

    2008-03-01

    Toll-like receptors (TLRs) are crucial pattern-recognition receptors (PRRs) for activation of innate and adapted immunity. TLR2 heterodimerizes with TLR1 or TLR6 to recognize multiple pathogen-associated molecular patterns (PAMPs) of fungi, Gram-positive pathogens, and mycobacteria. Receptor activation culminates in monocyte, T-helper (Th)1, and Th2 cytokine release. Single nucleotide polymorphisms (SNPs) Arg753Gln and Arg677Trp affect TLR2 responsiveness and may contribute to the course of sepsis, which is associated with substantial morbidity and mortality during intensive care treatment. We genotyped 325 critically ill patients with septic shock, and performed a detailed clinical follow-up with 47 of these patients. Here, we investigated whether distinct sepsis episodes result in defined plasma cytokine patterns, and whether cytokine profiles may be linked to the TLR2 polymorphisms. Blood sampling was done daily and microbiological testing was performed on a routine basis. DNA was extracted from whole blood and TLR2 SNPs were typed by pyrosequencing. Cytokines were measured by multiplexed array technologies and the leukocyte phenotype was determined by flow cytometry. Among the 325 ICU patients, 17 individuals (5.2%) were heterozygous for Arg753Gln. The SNP Arg677Trp was not found in any patient. Episodes of Gram-negative, Gram-positive, and Candida sepsis were recorded. During Gram-positive sepsis, the cytokine pattern did not differ between Arg753Gln heterozygous patients and wild type patients. By contrast, during Candida sepsis, the Arg753Gln heterozygous patients showed biomarker patterns that differed from wild type patients with elevated TNF-alpha plasma concentrations, but reduced IFN-gamma and IL-8 levels. In conclusion, TLR2 SNP Arg753Gln results in altered cytokine release in response to Candida but not to Gram-positive sepsis.

  2. 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

  3. 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

    2016-01-01

    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.

  4. Role of the C2A domain of synaptotagmin in transmitter release as determined by specific antibody injection into the squid giant synapse preterminal.

    PubMed Central

    Mikoshiba, K; Fukuda, M; Moreira, J E; Lewis, F M; Sugimori, M; Niinobe, M; Llinás, R

    1995-01-01

    Squid synaptotagmin (Syt) cDNA, including its open reading frame, was cloned and polyclonal antibodies were obtained in rabbits immunized with glutathione S-transferase (GST)-Syt-C2A. Binding assays indicated that the antibody, anti-Syt-C2A, recognized squid Syt and inhibited the Ca(2+)-dependent phospholipid binding to the C2A domain. This antibody, when injected into the preterminal at the squid giant synapse, blocked transmitter release in a manner similar to that previously reported for the presynaptic injection of members of the inositol high-polyphosphate series. The block was not accompanied by any change in the presynaptic action potential or the amplitude or voltage dependence of the presynaptic Ca2+ current. The postsynaptic potential was rather insensitive to repetitive presynaptic stimulation, indicating a direct effect of the antibody on the transmitter release system. Following block of transmitter release, confocal microscopical analysis of the preterminal junction injected with rhodamine-conjugated anti-Syt-C2A demonstrated fluorescent spots at the inner surface of the presynaptic plasmalemma next to the active zones. Structural analysis of the same preparations demonstrated an accumulation of synaptic vesicles corresponding in size and distribution to the fluorescent spots demonstrated confocally. Together with the finding that such antibody prevents Ca2+ binding to a specific receptor in the C2A domain, these results indicate that Ca2+ triggers transmitter release by activating the C2A domain of Syt. We conclude that the C2A domain is directly related to the fusion of synaptic vesicles that results in transmitter release. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7479868

  5. 46 CFR 160.062-6 - Procedure for approval.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 CFR 159.010. The independent laboratory will forward the report to the Commandant for examination...: 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 CFR 159.010. The independent laboratory will forward the report to the Commandant for examination...: 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...

  7. 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. PMID:27581561

  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. The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

    PubMed Central

    Nielsen, M. H.; Irvine, H.; Vedel, S.; Raungaard, B.; Beck-Nielsen, H.; Handberg, A.

    2016-01-01

    Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor-positive cells (TF+ MVs), were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation. PMID:26925191

  10. Specific receptor for hydrazine: mapping the in situ release of hydrazine in live cells and in an in vitro enzymatic assay.

    PubMed

    Ali, Firoj; A, Anila H; Taye, Nandaraj; Mogare, Devraj G; Chattopadhyay, Samit; Das, Amitava

    2016-05-01

    We report a new chemodosimetric reagent capable of detecting hydrazine in the presence of several other competing amine derivatives and ionic analytes of biological relevance. This reagent has been utilized for real time monitoring of in situ N2H4 release during the metabolism of a crucial tuberculosis drug, isoniazid, in live HepG2 cells. The fluorescence response of the reagent based on its specific reaction with N2H4 is used for developing an in vitro assay for aminoacylase-1.

  11. Methods and procedures for use of complement-fixation technique in type- and strain-specific diagnosis of influenza*†

    PubMed Central

    Lief, Florence S.; Henle, Werner

    1959-01-01

    It is now well established that there are two kinds of complement-fixing antigens of influenza virus: the soluble, type-specific, antigens, found mainly in infected tissue but also within the virus particle; and the virus, strain-specific, antigens, closely linked with the haemagglutinating component. For true results in complement-fixation testing in influenza, antigens or antisera of the one kind must be free of the other kind. This paper describes in detail the preparation of reagents for such testing and a variety of basic aspects of test procedures. PMID:13651922

  12. Inhibition of cytochrome c release by 10-N-nonyl acridine orange, a cardiolipin-specific dye, during myocardial ischemia-reperfusion in the rat.

    PubMed

    Zhang, Guo-Xing; Kimura, Shoji; Murao, Koji; Obata, Koji; Matsuyoshi, Hiroko; Takaki, Miyako

    2010-02-01

    The release of cytochrome c from the mitochondria to the cytosol is a critical step for downstream caspase-mediated apoptotic signal transduction in ischemia-reperfusion (I/R)-induced myocardial tissue injury. 10-N-nonyl acridine orange (NAO), a cardiolipin-specific dye, has been shown to inhibit Bid-mediated cytochrome c release from isolated mitochondria in vitro; however, the possible protective effects of NAO and the mechanisms underlying the protection from myocardial I/R-induced tissue injury in a rat model are unknown. Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion. All rats received either vehicle or NAO (100 microg/kg iv) 10 min before the occlusion. The infarct size in the heart at 24 h after reperfusion was significantly reduced in NAO-treated rats compared with vehicle-treated rats. NAO treatment significantly reduced the cytosolic cytochrome c contents and caspase-9 activity in the ischemic region but did not affect caspase-8 activity. Furthermore, NAO treatment markedly suppressed the translocation of truncated Bid, a proapoptotic Bcl-2 family member, to the mitochondrial fraction. NAO also suppressed the mitochondrial swelling and oxygen uptake stimulated by calcium overload. The results suggest that NAO possesses protective effects against myocardial I/R injury, which may be due to the suppression of cytochrome c release through blockade of truncated Bid translocation to mitochondria and inhibition of the opening of mitochondrial permeability transition pores.

  13. Role of the C2B domain of synaptotagmin in vesicular release and recycling as determined by specific antibody injection into the squid giant synapse preterminal.

    PubMed

    Fukuda, M; Moreira, J E; Lewis, F M; Sugimori, M; Niinobe, M; Mikoshiba, K; Llinás, R

    1995-11-01

    Synaptotagmin (Syt) is an inositol high-polyphosphate series [IHPS inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6-pentakisphosphate, and inositol 1,2,3,4,5,6-hexakisphosphate] binding synaptic vesicle protein. A polyclonal antibody against the C2B domain (anti-Syt-C2B), an IHPS binding site, was produced. The specificity of this antibody to the C2B domain was determined by comparing its ability to inhibit IP4 binding to the C2B domain with that to inhibit the Ca2+/phospholipid binding to the C2A domain. Injection of the anti-Syt-C2B IgG into the squid giant presynapse did not block synaptic release. Coinjection of IP4 and anti-Syt-C2B IgG failed to block transmitter release, while IP4 itself was a powerful synpatic release blocker. Repetitive stimulation to presynaptic fiber injected with anti-Syt-C2B IgG demonstrated a rapid decline of the postsynaptic response amplitude probably due to its block of synaptic vesicle recycling. Electron microscopy of the anti-Syt-C2B-injected presynapse showed a 90% reduction of the numbers of synaptic vesicles. These results, taken together, indicate that the Syt molecule is central, in synaptic vesicle fusion by Ca2+ and its regulation by IHPS, as well as in the recycling of synaptic vesicles.

  14. Role of the C2B domain of synaptotagmin in vesicular release and recycling as determined by specific antibody injection into the squid giant synapse preterminal.

    PubMed Central

    Fukuda, M; Moreira, J E; Lewis, F M; Sugimori, M; Niinobe, M; Mikoshiba, K; Llinás, R

    1995-01-01

    Synaptotagmin (Syt) is an inositol high-polyphosphate series [IHPS inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6-pentakisphosphate, and inositol 1,2,3,4,5,6-hexakisphosphate] binding synaptic vesicle protein. A polyclonal antibody against the C2B domain (anti-Syt-C2B), an IHPS binding site, was produced. The specificity of this antibody to the C2B domain was determined by comparing its ability to inhibit IP4 binding to the C2B domain with that to inhibit the Ca2+/phospholipid binding to the C2A domain. Injection of the anti-Syt-C2B IgG into the squid giant presynapse did not block synaptic release. Coinjection of IP4 and anti-Syt-C2B IgG failed to block transmitter release, while IP4 itself was a powerful synpatic release blocker. Repetitive stimulation to presynaptic fiber injected with anti-Syt-C2B IgG demonstrated a rapid decline of the postsynaptic response amplitude probably due to its block of synaptic vesicle recycling. Electron microscopy of the anti-Syt-C2B-injected presynapse showed a 90% reduction of the numbers of synaptic vesicles. These results, taken together, indicate that the Syt molecule is central, in synaptic vesicle fusion by Ca2+ and its regulation by IHPS, as well as in the recycling of synaptic vesicles. Images Fig. 1 Fig. 2 Fig. 3 PMID:7479869

  15. 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

  16. 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

  17. Restoration of abdominal wall integrity as a salvage procedure in difficult recurrent abdominal wall hernias using a method of wide myofascial release.

    PubMed

    Levine, J P; Karp, N S

    2001-03-01

    The management of primary and recurrent giant incisional hernias remains a complex and frustrating challenge even with multiple alloplastic and autogenous closure options. The purpose of this study was to develop a reconstructive technique of restoring abdominal wall integrity to a subcategory of patients, who have failed initial hernia therapy, by performing superior and lateral myofascial release. Over a 1.5-year period, 10 patients with previously unsuccessful treatment of abdominal wall hernias, using either primary repair or placement of synthetic material, were studied. The patients had either recurrence of the hernia or complications such as infections requiring removal of synthetic material. The hernias were not able to be treated with standard primary closure techniques or synthetic material. The average defect size was 19 x 9 cm. Each patient underwent wide lysis of bowel adhesions releasing the posterior abdominal wall fascia to the posterior axillary line, subcutaneous release of the anterior abdominal wall fascia to a similar level, and complete removal of any synthetic material (if present). The abdominal domain was reestablished by releasing the laterally retracted abdominal wall. The amount of available abdominal wall tissue was increased by wide release of the cephalic abdominal wall fascia overlying the costal margin and the external oblique fascia and muscle laterally. If needed, partial thickness of the internal oblique muscle and its anterior fascia were also released laterally to perform a tension-free primary closure of the defect. All repairs were closed with satisfactory functional and aesthetic results. All alloplastic material was removed. Fascial release was limited so as to close only the hernia defect without tension. No significant release of the rectus sheath and muscle was needed. Good, dynamic muscle function was noted postoperatively. All repairs have remained intact, and no further abdominal wall hernias have been noted on follow-up.

  18. A target-cell specific role for presynaptic Fmr1 in regulating glutamate release onto neocortical fast-spiking inhibitory neurons

    PubMed Central

    Patel, Ankur B.; Hays, Seth A.; Bureau, Ingrid; Huber, Kimberly M.; Gibson, Jay R.

    2013-01-01

    In the mouse model of Fragile X Syndrome, the Fmr1 knockout, local excitation of layer 4 fast-spiking (FS) inhibitory neurons is robustly decreased by 50%, but the mechanisms mediating this change are unknown. Here, we performed recordings in acutely prepared slices obtained from Fmr1 “mosaic” mice where Fmr1 is deleted in about half of all neurons, and we find that loss of presynaptic, but not postsynaptic, Fmr1 fully recapitulates the deficit. The change in connection strength is primarily due to a decrease in release probability indicating that FMRP normally positively regulates these processes. This change in presynaptic neurotransmitter release is observed both in the mosaic mice and in the constitutive Fmr1 knockout mice. Manipulations in release probability enabled both the mimic and rescue of the impaired function in this synaptic pathway. Loss of presynaptic Fmr1 has no effect on excitatory synapses onto excitatory neurons, indicating a target-cell specific function for presynaptic FMRP. Finally, we demonstrate that the excitation decrement onto FS neurons also exists in layer 5 of the Fmr1 KO suggesting a widespread role for presynaptic Fmr1 in the excitation of inhibitory neurons. In summary, we identify a novel function for presynaptic FMRP in promoting presynaptic neurotransmitter release, and we show that loss of this function accounts for impaired excitation of neocortical FS inhibitory neurons. These changes may contribute to the cognitive dysfunction and circuit hyperexcitability associated with Fragile X Syndrome – including patients with complete deletion of FMRP and those with mosaic expression of FMRP. PMID:23392687

  19. A Practical Procedure for Instituting a Chore and Allowance Program for Grade School Children: Specific Guidelines for Clinicians.

    ERIC Educational Resources Information Center

    Neul, Shari K. T.; Drabman, Ronald S.

    2001-01-01

    This article provides a use plan for instituting and maintaining a successful chore and allowance program for children. Specific guidelines are outlined regarding how to teach children basic money management skills. Explicit examples are offered for teaching these skills that can be easily adopted by parents and clinicians who specialize in…

  20. 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

  1. Differentiating specific job knowledge from implicit trait policies in procedural knowledge measured by a situational judgment test.

    PubMed

    Motowidlo, Stephan J; Beier, Margaret E

    2010-03-01

    This study compared validities of situational judgment test (SJT) scoring keys that were presumed to be differentially saturated with specific knowledge about effective job behavior and general knowledge about effective trait expression. The keys were based on subject matter experts' effectiveness judgments, undergraduates' effectiveness judgments, and graduate students' trait judgments. We used data reported earlier by Motowidlo, Dunnette, and Carter (1990) with managerial incumbents in telecommunication companies. All keys yielded valid relations with supervisory performance ratings. The key based on subject matter experts' judgments, however, explained criterion variance beyond the variance explained by the other keys. These results suggest that specific knowledge about effective job behavior and general knowledge about effective trait expression (i.e., implicit trait policies) contribute independently to variance in job performance.

  2. 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/.

  3. 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.

  4. 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...

  5. 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.

  6. Phylogenetic footprinting reveals evolutionarily conserved regions of the gonadotropin-releasing hormone gene that enhance cell-specific expression.

    PubMed

    Givens, Marjory L; Kurotani, Reiko; Rave-Harel, Naama; Miller, Nichol L G; Mellon, Pamela L

    2004-12-01

    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.

  7. 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.

  8. 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

  9. 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.

  10. 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

    2016-01-01

    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

  11. Basolateral amygdala rapid glutamate release encodes an outcome-specific representation vital for reward-predictive cues to selectively invigorate reward-seeking actions

    PubMed Central

    Malvaez, Melissa; Greenfield, Venuz Y.; Wang, Alice S.; Yorita, Allison M.; Feng, Lili; Linker, Kay E.; Monbouquette, Harold G.; Wassum, Kate M.

    2015-01-01

    Environmental stimuli have the ability to generate specific representations of the rewards they predict and in so doing alter the selection and performance of reward-seeking actions. The basolateral amygdala participates in this process, but precisely how is unknown. To rectify this, we monitored, in near-real time, basolateral amygdala glutamate concentration changes during a test of the ability of reward-predictive cues to influence reward-seeking actions (Pavlovian-instrumental transfer). Glutamate concentration was found to be transiently elevated around instrumental reward seeking. During the Pavlovian-instrumental transfer test these glutamate transients were time-locked to and correlated with only those actions invigorated by outcome-specific motivational information provided by the reward-predictive stimulus (i.e., actions earning the same specific outcome as predicted by the presented CS). In addition, basolateral amygdala AMPA, but not NMDA glutamate receptor inactivation abolished the selective excitatory influence of reward-predictive cues over reward seeking. These data the hypothesis that transient glutamate release in the BLA can encode the outcome-specific motivational information provided by reward-predictive stimuli. PMID:26212790

  12. An Efficient Procedure for Marker-Free Mutagenesis of S. coelicolor by Site-Specific Recombination for Secondary Metabolite Overproduction

    PubMed Central

    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. PMID:23409083

  13. Site-specific (18)F-labeling of the protein hormone leptin using a general two-step ligation procedure.

    PubMed

    Flavell, Robert R; Kothari, Paresh; Bar-Dagan, Maya; Synan, Michael; Vallabhajosula, Shankar; Friedman, Jeffrey M; Muir, Tom W; Ceccarini, Giovanni

    2008-07-16

    The protein hormone leptin acts to regulate body fat and energy expenditure. Resistance to this hormone is implicated in human obesity and its pathophysiological consequences. In order to gain insight into the mechanism of leptin resistance, an (18)F-labeled derivative was developed to study the biodistribution of the hormone using positron emission tomography (PET). A two-step, site specific ligation approach was developed for this purpose, in which an aminooxy-reactive group was incorporated at the C-terminus of leptin using expressed protein ligation (EPL), which was subsequently derivatized with [ (18)F]fluorobenzaldehyde using an aniline-accelerated radiochemical oximation reaction. The modified hormone was shown to be biologically active in vitro and in vivo, and it was applied to PET imaging in ob/ ob mice. These protocols will allow for the routine production of site-specifically (18)F radiolabeled leptin, as well as other proteins, for use in PET imaging in systems from mouse to man.

  14. Separation of one-pot procedure released O-glycans as 1-phenyl-3-methyl-5-pyrazolone derivatives by hydrophilic interaction and reversed-phase liquid chromatography followed by identification using electrospray mass spectrometry and tandem mass spectrometry.

    PubMed

    Wang, Chengjian; Yuan, Jiangbei; Wang, Zhongfu; Huang, Linjuan

    2013-01-25

    Qualitative and quantitative analysis of naturally-occurring complex glycans is essential for glycomics, which focuses on the studies of structure-function correlations of saccharides. We previously reported a one-pot procedure for the non-reductive release from glycoproteins and in situ labeling with 1-phenyl-3-methyl-5-pyrazolone (PMP) of O-glycans (C. Wang et al., Proteomics 11 (2011) 4229). Here we describe an HPLC-based O-glycan analytical strategy that combines a range of techniques including the one-pot procedure, independent separation by hydrophilic interaction liquid chromatography (HILIC) and reversed-phase high-performance liquid chromatography (RP-HPLC) and identification by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). The complex mixtures of both neutral and sialylated O-glycans as bis-PMP derivatives released from glycoproteins using the one-pot procedure could be well separated by HILIC based on their size or by RP-HPLC depending on the type of linkage and their resulting three-dimensional (3D) structure, and their structure could be characterized by the ESI-MS and MS/MS analysis of the eluted glycan fractions. The validity of the current strategy was confirmed by the analysis of O-glycans released by the one-pot procedure from some standard glycoproteins, including porcine stomach mucin (PSM), bovine submaxillary mucin (BSM) and bovine fetuin. The applicability of the current method to complex biological samples was also demonstrated by the analysis of mucin-type glycans from fetal bovine serum (FBS) and frog egg-jelly coat (FEC). This strategy, a powerful analytical tool that features the combination of different techniques, is useful for the qualitative and quantitative O-glycan analysis of more complex biological samples and has a potential for constructing an O-glycan analysis and structure database.

  15. 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. PMID:15198539

  16. 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.

  17. 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.

  18. Metatarsalgia and Morton's Disease: Comparison of Outcomes Between Open Procedure and Neurectomy Versus Percutaneous Metatarsal Osteotomies and Ligament Release With a Minimum of 2 Years of Follow-Up.

    PubMed

    Bauer, Thomas; Gaumetou, Elodie; Klouche, Shahnaz; Hardy, Philippe; Maffulli, Nicola

    2015-01-01

    The present study compared the clinical results of open neurectomy versus a percutaneous procedure for Morton's disease. This was a retrospective study comparing the functional results after 2 surgical procedures: open neurectomy and a percutaneous procedure (with deep transverse metatarsal ligament release and distal metatarsal osteotomies). The present study included 52 patients (26 in each group), and the mean follow-up period was 4 (range 2 to 7) years. The patient evaluation criteria included the presence of painful symptoms of Morton's disease, American Orthopaedic Foot and Ankle Society (AOFAS) functional scale score, patient satisfaction, and delay for recovery. Percutaneous treatment of Morton's disease and open neurectomy produced complete relief of pain in 25 of 26 patients in each group. At the latest follow-up visit, the mean AOFAS score had significantly improved from 36 ± 11 preoperatively to a mean of 89 ± 18 (p < .001). After 2 years, the functional improvement obtained with the percutaneous procedure persisted, with a stable AOFAS score (96 ± 10). Persistent metatarsalgia was reported by patients who had undergone open neurectomy, with a significantly decreased AOFAS score (81 ± 21, p = .009). The percutaneous procedure for Morton's disease provided excellent functional outcomes (AOFAS score >90) significantly more often with a shorter delay than after open neurectomy (p = .03). At the latest follow-up visit, metatarsalgia due to plantar hyperpressure or bursitis and requiring plantar orthotics was present in 11 of 26 patients (44%) after open neurectomy and in 1 of 26 patients (4%) after the percutaneous procedure (p = .002). Percutaneous treatment of Morton's disease is a reliable procedure providing results as good as those after open neurectomy, with significantly better outcomes in the longer term and a lower rate of late metatarsalgia.

  19. 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...

  20. Determining optimal cytotoxic activity of human Her2neu specific CD8 T cells by comparing the Cr51 release assay to the xCELLigence system.

    PubMed

    Erskine, Courtney L; Henle, Andrea M; Knutson, Keith L

    2012-01-01

    Cytotoxic CD8 T cells constitute a subgroup of T cells that are capable of inducing the death of infected or malignant host cells. These cells express a specialized receptor, called the T cell receptor (TCR), which can recognize a specific antigenic peptide bound to HLA class I molecules. Engagement of infected cells or tumor cells through their HLA class I molecule results in production of lytic molecules such as granzymes and perforin resulting in target cell death. While it is useful to determine frequencies of antigen-specific CD8 T cells using assays such as the ELIspot or flow cytometry, it is also helpful to ascertain the strength of CD8 T cell responses using cytotoxicity assays. The most recognizable assay for assessing cytotoxic function is the Chromium Release Assay (CRA), which is considered a standard assay. The CRA has several limitations, including exposure of cells to gamma radiation, lack of reproducibility, and a requirement for large numbers of cells. Over the past decade, there has been interest in adopting new strategies to overcome these limitations. Newer approaches include those that measure caspase release , BLT esterase activity and surface expression of CD107. The impedance-based assay, using the Roche xCelligence system, was examined in the present paper for its potential as an alternative to the CRA. Impedance or opposition to an electric current occurs when adherent tumor cells bind to electrode plates. Tumor cells detach following killing and electrical impedance is reduced which can be measured by the xCelligence system. The ability to adapt the impedance-based approach to assess cell-mediated killing rests on the observation that T cells do not adhere tightly to most surfaces and do not appear to have much impact on impedance thus diminishing any concern of direct interference of the T cells with the measurement. Results show that the impedance-based assay can detect changes in the levels of antigen-specific cytotoxic CD8 T cells

  1. Cell type-specific activation of metabolism reveals that beta-cell secretion suppresses glucagon release from alpha-cells in rat pancreatic islets.

    PubMed

    Takahashi, Rui; Ishihara, Hisamitsu; Tamura, Akira; Yamaguchi, Suguru; Yamada, Takahiro; Takei, Daisuke; Katagiri, Hideki; Endou, Hitoshi; Oka, Yoshitomo

    2006-02-01

    Abnormal glucagon secretion is often associated with diabetes mellitus. However, the mechanisms by which nutrients modulate glucagon secretion remain poorly understood. Paracrine modulation by beta- or delta-cells is among the postulated mechanisms. Herein we present further evidence of the paracrine mechanism. First, to activate cellular metabolism and thus hormone secretion in response to specific secretagogues, we engineered insulinoma INS-1E cells using an adenovirus-mediated expression system. Expression of the Na+-dependent dicarboxylate transporter (NaDC)-1 resulted in 2.5- to 4.6-fold (P < 0.01) increases in insulin secretion in response to various tricarboxylic acid cycle intermediates. Similarly, expression of glycerol kinase (GlyK) increased insulin secretion 3.8- or 4.2-fold (P < 0.01) in response to glycerol or dihydroxyacetone, respectively. This cell engineering method was then modified, using the Cre-loxP switching system, to activate beta-cells and non-beta-cells separately in rat islets. NaDC-1 expression only in non-beta-cells, among which alpha-cells are predominant, caused an increase (by 1.8-fold, P < 0.05) in glucagon secretion in response to malate or succinate. However, the increase in glucagon release was prevented when NaDC-1 was expressed in whole islets, i.e., both beta-cells and non-beta-cells. Similarly, an increase in glucagon release with glycerol was observed when GlyK was expressed only in non-beta-cells but not when it was expressed in whole islets. Furthermore, dicarboxylates suppressed basal glucagon secretion by 30% (P < 0.05) when NaDC-1 was expressed only in beta-cells. These data demonstrate that glucagon secretion from rat alpha-cells depends on beta-cell activation and provide insights into the coordinated mechanisms underlying hormone secretion from pancreatic islets.

  2. A microextraction procedure based on a task-specific ionic liquid for the separation and preconcentration of lead ions from red lipstick and pine leaves.

    PubMed

    Saljooqi, Asma; Shamspur, Tayebeh; Mohamadi, Maryam; Afzali, Daryoush; Mostafavi, Ali

    2015-05-01

    First, the extraction and preconcentration of ultratrace amounts of lead(II) ions was performed using microliter volumes of a task-specific ionic liquid. The remarkable properties of ionic liquids were added to the advantages of microextraction procedure. The ionic liquid used was trioctylmethylammonium thiosalicylate, which formed a lead thiolate complex due to the chelating effect of the ortho-positioned carboxylate relative to thiol functionality. So, trioctylmethylammonium thiosalicylate played the roles of both chelating agent and extraction solvent simultaneously. Hence, there is no need to use a ligand. The main parameters affecting the efficiency of the method were investigated and optimized. Under optimized conditions, this approach showed a linear range of 2.0-24.0 ng/mL with a detection limit of 0.0010 ng/mL. The proposed method was applied to the extraction and preconcentration of lead from red lipstick and pine leaves samples prior to electrothermal atomic absorption spectroscopic determination.

  3. A microextraction procedure based on a task-specific ionic liquid for the separation and preconcentration of lead ions from red lipstick and pine leaves.

    PubMed

    Saljooqi, Asma; Shamspur, Tayebeh; Mohamadi, Maryam; Afzali, Daryoush; Mostafavi, Ali

    2015-05-01

    First, the extraction and preconcentration of ultratrace amounts of lead(II) ions was performed using microliter volumes of a task-specific ionic liquid. The remarkable properties of ionic liquids were added to the advantages of microextraction procedure. The ionic liquid used was trioctylmethylammonium thiosalicylate, which formed a lead thiolate complex due to the chelating effect of the ortho-positioned carboxylate relative to thiol functionality. So, trioctylmethylammonium thiosalicylate played the roles of both chelating agent and extraction solvent simultaneously. Hence, there is no need to use a ligand. The main parameters affecting the efficiency of the method were investigated and optimized. Under optimized conditions, this approach showed a linear range of 2.0-24.0 ng/mL with a detection limit of 0.0010 ng/mL. The proposed method was applied to the extraction and preconcentration of lead from red lipstick and pine leaves samples prior to electrothermal atomic absorption spectroscopic determination. PMID:25735972

  4. NASPE expert consensus document: use of i.v. (conscious) sedation/analgesia by nonanesthesia personnel in patients undergoing arrhythmia specific diagnostic, therapeutic, and surgical procedures.

    PubMed

    Bubien, R S; Fisher, J D; Gentzel, J A; Murphy, E K; Irwin, M E; Shea, J B; Dick, M; Ching, E; Wilkoff, B L; Benditt, D G

    1998-02-01

    Use of IV (Conscious) Sedation/Analgesia by Nonanesthesia Personnel in Patients Undergoing Arrhythmia Specific Diagnostic, Therapeutic, and Surgical Procedures. This article is intended to inform practitioners, payers, and other interested parties of the opinion of the North American Society of Pacing and Electrophysiology (NASPE) concerning evolving areas of clinical practice or technologies or both, that are widely available or are new to the practice community. Expert consensus documents are so designated because the evidence base and experience with the technology or clinical practice are not yet sufficiently well developed, or rigorously controlled trials are not yet available that would support a more definitive statement. This article has been endorsed by the American College of Cardiology, October 1997. PMID:9507538

  5. A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release

    PubMed Central

    Jose, Antony M.; Bany, I. Amy; Chase, Daniel L.; Koelle, Michael R.

    2007-01-01

    Transient receptor potential (TRP) channel subunits form homotetramers that function in sensory transduction. Heteromeric channels also form, but their physiological subunit compositions and functions are largely unknown. We found a dominant-negative mutant of the C. elegans TRPV (vanilloid-type) subunit OCR-2 that apparently incorporates into and inactivates OCR-2 homomers as well as heteromers with the TRPV subunits OCR-1 and -4, resulting in a premature egg-laying defect. This defect is reproduced by knocking out all three OCR genes, but not by any single knockout. Thus a mixture of redundant heteromeric channels prevents premature egg laying. These channels, as well as the G-protein Gαo, function in neuroendocrine cells to promote release of neurotransmitters that block egg laying until eggs filling the uterus deform the neuroendocrine cells. The TRPV channel OSM-9, previously suggested to be an obligate heteromeric partner of OCR-2 in sensory neurons, is expressed in the neuroendocrine cells but has no detectable role in egg laying. Our results identify a specific set of heteromeric TRPV channels that redundantly regulate neuroendocrine function and show that a subunit combination that functions in sensory neurons is also present in neuroendocrine cells but has no detectable function in these cells. PMID:17057248

  6. 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

    2015-12-01

    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. PMID:26476917

  7. 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

    2015-12-01

    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.

  8. High background rates of positive tuberculosis-specific interferon-γ release assays in a low prevalence region of UK: a surveillance study

    PubMed Central

    2012-01-01

    Background Background rates of latent tuberculosis infection in low prevalence regions of Britain are unknown. These would be valuable data for interpreting positive IGRA results, and guiding cost-benefit analyses. The management of a large outbreak of tuberculosis occurring in a rural district hospital provided an opportunity to determine the background rates and epidemiology of IGRA-positivity amongst unselected hospital patients in a low-prevalence region of U.K. Methods As part of a public health surveillance project we identified 445 individuals exposed to the index cases for clinical assessment and testing by a TB-specific interferon-γ release assay (IGRA): T-Spot.TB. Uniquely, an additional comparator group of 191 age-matched individuals without specific recent exposure, but with a similar age distribution and demographic, were recruited from the same wards where exposure had previously occurred, to undergo assessment by questionnaire and IGRA. Results Rates of IGRA positivity were 8.7% (95%CI, 4.2-13, n=149) amongst unexposed patients, 9.5%(3.0-22, n=21) amongst unexposed staff, 22%(14–29, n=130) amongst exposed patients, 11%(6.1-16, n=142) amongst exposed staff. Amongst the individuals without history of recent exposure to the outbreak, IGRA-positivity was associated with prior TB treatment (OR11, P.04) and corticosteroid use (OR5.9, P.02). Background age-specific prevalences of IGRA-positivity amongst unexposed individuals were: age <40 0%(N/A), age 40–59 15%(12–29), age 60–79 7.0%(1.1-13), age≥80 10%(5.9-19). Conclusions Background rates of IGRA-positivity remain high amongst unselected white-Caucasian hospital inpatients in U.K. These data will aid interpretation of future outbreak studies. As rates peak in the 5th and 6th decade, given an ageing population and increasing iatrogenic immunosuppression, reactivation of LTBI may be a persistent hazard in this population for several decades to come. PMID:23216965

  9. Specific functions of the Rep and Rep' proteins of porcine circovirus during copy-release and rolling-circle DNA replication

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Prospective multi-centre Voxel Based Morphometry study employing scanner specific segmentations: Procedure development using CaliBrain structural MRI data

    PubMed Central

    2009-01-01

    Background Structural Magnetic Resonance Imaging (sMRI) of the brain is employed in the assessment of a wide range of neuropsychiatric disorders. In order to improve statistical power in such studies it is desirable to pool scanning resources from multiple centres. The CaliBrain project was designed to provide for an assessment of scanner differences at three centres in Scotland, and to assess the practicality of pooling scans from multiple-centres. Methods We scanned healthy subjects twice on each of the 3 scanners in the CaliBrain project with T1-weighted sequences. The tissue classifier supplied within the Statistical Parametric Mapping (SPM5) application was used to map the grey and white tissue for each scan. We were thus able to assess within scanner variability and between scanner differences. We have sought to correct for between scanner differences by adjusting the probability mappings of tissue occupancy (tissue priors) used in SPM5 for tissue classification. The adjustment procedure resulted in separate sets of tissue priors being developed for each scanner and we refer to these as scanner specific priors. Results Voxel Based Morphometry (VBM) analyses and metric tests indicated that the use of scanner specific priors reduced tissue classification differences between scanners. However, the metric results also demonstrated that the between scanner differences were not reduced to the level of within scanner variability, the ideal for scanner harmonisation. Conclusion Our results indicate the development of scanner specific priors for SPM can assist in pooling of scan resources from different research centres. This can facilitate improvements in the statistical power of quantitative brain imaging studies. PMID:19445668

  11. Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice.

    PubMed

    Schreurs, B G; Oh, M M; Alkon, D L

    1996-03-01

    1. Using a rabbit cerebellar slice preparation, we stimulated a classical conditioning procedure by stimulating parallel fiber inputs to Purkinje cells with the use of a brief, high-frequency train of eight constant-current pulses 80 ms before climbing fiber inputs to the same Purkinje cell were stimulated with the use of a brief, lower frequency train of three constant-current pulses. In all experiments, we assessed the effects of stimulation by measuring the peak amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single parallel fiber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs underwent a long-term (> 20 min) reduction in peak amplitude (30%) after paired stimulation of the parallel and climbing fibers but not after unpaired or parallel fiber alone stimulation. We call this phenomenon pairing-specific long-term depression (PSD). 3. Facilitation of the peak amplitude of a second EPSP elicited by a parallel fiber train occurred both before and after paired stimulation suggesting that the locus of depression was not presynaptic. Depression of the peak amplitude of a depolarizing response to focal application of glutamate following pairings of parallel and climbing fiber stimulation added support to a suggested postsynaptic locus of the PSD effect. 4. The application of aniracetam potentiated EPSP peak amplitude by 40%, but these values returned to baseline as a result of pairings. With the removal of aniracetam from the bath 20 min after pairings, normal levels of pairing-specific EPSP depression were observed, indicating that the effect did not result from direct desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors. 5. Incubation of slices in the protein kinase inhibitor H-7 potentiated EPSP peak amplitudes slightly (9%), but peak amplitudes returned to baseline levels after pairings. The net reduction in EPSP peak amplitude of < 10% after pairings suggested that H-7 partially

  12. 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.

  13. 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. PMID:26655589

  14. Specific absorption rate in neonates undergoing magnetic resonance procedures at 1.5 T and 3 T

    PubMed Central

    Beqiri, Arian; Price, Anthony N.; Teixeira, Jose Nuno; Hand, Jeffrey W.; Hajnal, Joseph V.

    2015-01-01

    MRI is finding increased clinical use in neonatal populations; the extent to which electromagnetic models used for quantification of specific absorption rate (SAR) by commercial MRI scanners accurately reflect this alternative scenario is unclear. This study investigates how SAR predictions relating to adults can be related to neonates under differing conditions when imaged using 1.5 T and 3 T MRI scanners. Electromagnetic simulations were produced in neonatal subjects of different sizes and positions within a generic MRI body transmit device operating at both 64 MHz and 128 MHz, corresponding to 1.5 T and 3 T MRI scanners, respectively. An adult model was also simulated, as was a spherical salt‐water phantom, which was also used in a calorimetry experiment. The SAR in neonatal subjects was found to be less than that experienced in an adult in all scenarios; however, the overestimation factor was variable. For example a 3 T body scan resulting in local 10 g SAR of 10.1 W kg−1 in an adult would deposit 2.6 W kg−1 in a neonate: an approximately fourfold difference. The SAR experienced by neonatal subjects undergoing MRI is lower than that in adults in equivalent situations. If the safety of such procedures is assessed using adult‐appropriate models then the result is a conservative estimate. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. PMID:25594939

  15. 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.

  16. Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release.

    PubMed Central

    Zini, S; Fournie-Zaluski, M C; Chauvel, E; Roques, B P; Corvol, P; Llorens-Cortes, C

    1996-01-01

    Angiotensin (Ang) II and Ang III are two peptide effectors of the brain renin-angiotensin system that participate in the control of blood pressure and increase water consumption and vasopressin release. In an attempt to delineate the respective roles of these peptides in the regulation of vasopressin secretion, their metabolic pathways and their effects on vasopressin release were identified in vivo. For this purpose, we used recently developed selective inhibitors of aminopeptidase A (APA) and aminopeptidase N (APN), two enzymes that are believed to be responsible for the N-terminal cleavage of Ang II and Ang III, respectively. Mice received [3H]Ang II intracerebroventricularly (i.c.v.) in the presence or absence of the APN inhibitor, EC33 (3-amino-4-thio-butyl sulfonate) of the APN inhibitor, EC27 (2-amino-pentan-1,5-dithiol). [3H]Ang II and [3H]Ang III levels were evaluated from hypothalamus homogenates by HPLC. EC33 increased the half-life of [3H]Ang II 2.6-fold and completely blocked the formation of [3H]Ang III, whereas EC27 increased the half-life of [3H]Ang III 2.3-fold. In addition, the effects of EC33 and EC27 on Ang-induced vasopressin release were studied in mice. Ang II was injected i.c.v. in the presence or absence of EC33, and plasma vasopressin levels were estimated by RIA. While vasopressin levels were increased 2-fold by Ang II (5 ng), EC33 inhibited Ang II-induced vasopressin release in a dose-dependent manner. In contrast, EC27 injected alone increased in a dose-dependent manner vasopressin levels. The EC27-induced vasopressin release was completely blocked by the coadministration of the Ang receptor antagonist (Sar1-Ala8) Ang II. These results demonstrate for the first time that (i) APA and APN are involved in vivo in the metabolism of brain Ang II and Ang III, respectively, and that (ii) the action of Ang II on vasopressin release depends upon the prior conversion of Ang II to Ang III. This shows that Ang III behaves as one of the main

  17. 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).

  18. 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.

  19. 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. PMID:27051284

  20. 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

  1. 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. PMID:25662498

  2. 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.

  3. 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…

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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. PMID:25051610

  10. 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.

  11. Procedural Due Process in the Context of Public Higher Education: The Identification of Specific Due Process Components Impacting the Termination of Tenured Faculty.

    ERIC Educational Resources Information Center

    Habecker, Eugene B.

    Due process procedures that are judicially required in public colleges and universities when tenured faculty are involuntarily terminated for cause were identified through analysis of federal case law. Other areas of case law pertaining to due process were reviewed, including student dismissals from public colleges and universities, and property…

  12. 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. PMID:26447666

  13. 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…

  14. 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.

  15. 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.

  16. Interpretation and optimization of the dissolution specifications for a modified release product with an in vivo-in vitro correlation (IVIVC).

    PubMed

    Hayes, Siobhán; Dunne, Adrian; Smart, Trevor; Davis, John

    2004-03-01

    This article considers the in vivo significance attached to in vitro dissolution testing. Almost invariably, the in vitro dissolution test is interpreted in terms of bioequivalence. The literature that describes methods for setting in vitro dissolution specifications is reviewed. The most common interpretation of these specifications is a deterministic one, that is, those batches passing the dissolution specifications would be bioequivalent with the reference if tested in vivo and those failing the dissolution specifications would not be bioequivalent if tested in vivo. Due to random variation, the deterministic interpretation is not appropriate. Instead, we need to consider the conditional probability that a batch that has passed the in vitro dissolution test would demonstrate bioequivalence if tested in vivo, and that a batch known to have failed the in vitro dissolution test would demonstrate bioinequivalence if tested in vivo. One way to estimate these probabilities is by means of a simulated experiment in which the production and testing (in vivo and in vitro) of a large number of batches is computer simulated. Such a simulation can only be performed if the relationship between the in vitro dissolution characteristics and the in vivo performance of the product has been modeled. These models are generally referred to as in vivo-in vitro correlations (IVIVC). The results of one such experiment are described. The above-mentioned conditional probabilities are shown to depend on the choice of dissolution specifications. This result leads to the notion of optimal dissolution specifications. However, both of the conditional probabilities cannot be maximized simultaneously. The probability of making a correct decision on the basis of the in vitro dissolution test is introduced as a possible optimality criterion. This probability is a linear combination of the two conditional probabilities of interest. Using this criterion, the optimal dissolution specifications can be

  17. 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

    2016-09-01

    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. PMID:27438964

  18. 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

    2016-09-01

    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.

  19. 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.

  20. Procedural knowledge

    SciTech Connect

    Georgeff, M.P.; Lansky, A.L.

    1986-10-01

    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, our 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.

  1. A sequence-specific DNA binding small molecule triggers the release of immunogenic signals and phagocytosis in a model of B-cell lymphoma.

    PubMed

    Kang, JeenJoo S; Dervan, Peter B

    2015-11-01

    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

  2. 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

  3. 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.

  4. 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.

  5. 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/

  6. 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/

  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 PMID:27054474

  8. 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.

  9. 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

  10. Ultrasound-Assisted Endoscopic Carpal Tunnel Release.

    PubMed

    Ohuchi, Hiroshi; Hattori, Soichi; Shinga, Kotaro; Ichikawa, Ken; Yamada, Shin

    2016-06-01

    Various surgical procedures for carpal tunnel syndrome exist, such as open release, ultrasound-guided percutaneous release, and endoscopic release. Postoperative pain, scarring, and slow recovery to normal function are reported complications of open release. Damage to vessels and the median nerve and its branches underlying the transverse carpal ligament is a reported complication of ultrasound-guided percutaneous release. Damage to the superficial palmar arch and incomplete release are reported complications of endoscopic release. By performing endoscopic carpal tunnel release with ultrasound assistance, we could visualize neurovascular structures directly with the endoscope and also indirectly with ultrasound to minimize complications. We could also evaluate the morphologic changes of the median nerve dynamically before and after the release. We discuss the technique for this procedure and outline pearls and pitfalls for success. PMID:27656366

  11. Measurement of bile acid synthesis in man by release of 14CO2 from [26-14C]cholesterol: comparison to isotope dilution and assessment of optimum cholesterol specific activity.

    PubMed

    Mitchell, J C; Stone, B G; Duane, W C

    1992-01-01

    Bile acid synthesis can be measured as release of 14CO2 from [26-14C]cholesterol divided by cholesterol specific activity, but this method has not been validated in human subjects. We made twelve comparisons of this CO2 method to standard isotope dilution in six normal subjects and found a mean discrepancy of 6%. Linear regression analysis of one value with respect to the other revealed a correlation coefficient of 0.83 (P less than 0.01), a Y-intercept close to zero (-4.98) and a slope close to 1 (1.06), suggesting good correspondence between the two methods. To assess the potential for error arising from use of serum cholesterol to estimate specific activity of cholesterol used for bile acid synthesis, we compared synthesis measured using serum free cholesterol specific activity to that measured using bile cholesterol specific activity, which is known to be near isotopic equilibrium with the precursor pool used for bile acid synthesis. Synthesis calculated in these two ways differed by less than 10%. The data indicate that the CO2 method using either serum or bile cholesterol specific activity provides a valid estimate of bile acid synthesis in man.

  12. (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.

  13. 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.

  14. 40 CFR 302.8 - Continuous releases.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... CFR part 355, which require initial telephone and written notifications of continuous releases to be... release data, engineering estimates, knowledge of operating procedures, or best professional judgment to... requirements of this section, the person in charge may rely on recent release data, engineering estimates,...

  15. 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. PMID:24526727

  16. (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. PMID:26873673

  17. 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.

  18. A controlled-release microchip.

    PubMed

    Santini, J T; Cima, M J; Langer, R

    1999-01-28

    Much previous work in methods of achieving complex drug-release patterns has focused on pulsatile release from polymeric materials in response to specific stimuli, such as electric or magnetic fields, exposure to ultrasound, light or enzymes, and changes in pH or temperature. An alternative method for achieving pulsatile release involves using microfabrication technology to develop active devices that incorporate micrometre-scale pumps, valves and flow channels to deliver liquid solutions. Here we report a solid-state silicon microchip that can provide controlled release of single or multiple chemical substances on demand. The release mechanism is based on the electrochemical dissolution of thin anode membranes covering microreservoirs filled with chemicals in solid, liquid or gel form. We have conducted proof-of-principle release studies with a prototype microchip using gold and saline solution as a model electrode material and release medium, and we have demonstrated controlled, pulsatile release of chemical substances with this device.

  19. Amino acid substitutions at position 97 in HLA-A2 segregate cytolysis from cytokine release in MART-1/Melan-A peptide AAGIGILTV-specific cytotoxic T lymphocytes.

    PubMed

    Maeurer, M J; Chan, H W; Karbach, J; Salter, R D; Knuth, A; Lotze, M T; Storkus, W J

    1996-11-01

    CD8+ T lymphocytes recognize antigenic peptides presented by major histocompatibility complex (MHC) class I molecules. Individual peptide termini appear to be fixed at the C- and N-terminal ends. In contrast, central peptide side chains residues may point in different directions and exhibit limited flexibility, dependent on the MHC class I structural variation. For instance, position 97 in HLA-A201 has been shown to shift individual peptide species into different coordinations, one oriented towards the peptide N terminus, or more towards the C-terminal end. The conformational shape of such non-anchor peptide residues may affect the affinity of MHC/peptide/TCR interaction, resulting in quantitative, or qualitative different T cell effector functions. To characterize the impact of different amino acid residues occupying position 97 in HLA-A2 on peptide binding and presentation to CTL, we generated a panel of mutated HLA-A2 molecules containing either M, K, T, V, G, Q, W, P or H at position 97. The HLA-A0201 presented melanoma-associated MART-1/Melan-A derived peptide AAGIGILTV was employed to assess the impact of such position-97 mutations on HLA-A2 in peptide binding measured in an HLA-A2 reconstitution assay and presentation to AAGIGILTV-specific polyclonal or clonal T lymphocytes as measured by cytotoxicity, or interferon (IFN)-gamma and granulocyte/ macrophage colony-stimulating factor (GM-CSF) secretion. The high-affinity AAGIGILTV peptide bound to all position-97 mutants, albeit with differential efficiencies, and elicited specific release of IFN-gamma and GM-CSF by CTL. CTL responses were triggered only by the HLA-A2 wild type, by HLA-A2-H97 (histidine position 97 mutant), and HLA-A2-W97. The HLA-A2-M97 presenting molecule elicited enhanced cytokine release and CTL effector functions by polyclonal and by clonal effector T cells. These results indicate that MHC class I-bound peptides can trigger specific cytokine release by effector T cells independently of

  20. Domain contributions to signaling specificity differences between Ras-guanine nucleotide releasing factor (Ras-GRF) 1 and Ras-GRF2.

    PubMed

    Jin, Shan-Xue; Bartolome, Christopher; Arai, Junko A; Hoffman, Laurel; Uzturk, B Gizem; Kumar-Singh, Rajendra; Waxham, M Neal; Feig, Larry A

    2014-06-01

    Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2) constitute a family of similar calcium sensors that regulate synaptic plasticity. They are both guanine exchange factors that contain a very similar set of functional domains, including N-terminal pleckstrin homology, coiled-coil, and calmodulin-binding IQ domains and C-terminal Dbl homology Rac-activating domains, Ras-exchange motifs, and CDC25 Ras-activating domains. Nevertheless, they regulate different forms of synaptic plasticity. Although both GRF proteins transduce calcium signals emanating from NMDA-type glutamate receptors in the CA1 region of the hippocampus, GRF1 promotes LTD, whereas GRF2 promotes θ-burst stimulation-induced LTP (TBS-LTP). GRF1 can also mediate high frequency stimulation-induced LTP (HFS-LTP) in mice over 2-months of age, which involves calcium-permeable AMPA-type glutamate receptors. To add to our understanding of how proteins with similar domains can have different functions, WT and various chimeras between GRF1 and GRF2 proteins were tested for their abilities to reconstitute defective LTP and/or LTD in the CA1 hippocampus of Grf1/Grf2 double knock-out mice. These studies revealed a critical role for the GRF2 CDC25 domain in the induction of TBS-LTP by GRF proteins. In contrast, the N-terminal pleckstrin homology and/or coiled-coil domains of GRF1 are key to the induction of HFS-LTP by GRF proteins. Finally, the IQ motif of GRF1 determines whether a GRF protein can induce LTD. Overall, these findings show that for the three forms of synaptic plasticity that are regulated by GRF proteins in the CA1 hippocampus, specificity is encoded in only one or two domains, and a different set of domains for each form of synaptic plasticity.

  1. Toggle release

    NASA Technical Reports Server (NTRS)

    Graves, Thomas Joseph (Inventor); Yang, Robert Alexander (Inventor); Brown, Christopher William (Inventor)

    1988-01-01

    The invention relates to a pyrotechnic actuated release mechanism which is mechanically two fault tolerant for effecting release. It is particularly well suited for releasably connecting structures to be used in the space environment or in other aerospace applications. The device comprises a fastener plate and fastener body, each attachable to either one of a pair of structures to be joined. The fastener plate and the body are fastenable by a toggle 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 and adapted for limited pivotal movement therein, the toggle is restrained by three retractable latching pins. Each pin is individually retractable by combustion of a pyrotechnic charge. While retraction of all three pins releases the toggle, the fastener is mechanically two fault tolerant since the failure of any single 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 is mounted on the fastener plate as a support for the socket mounting of the toggle whereby its selective axial movement provides a means for pre-loading the toggle.

  2. A universal procedure for the [¹⁸F]trifluoromethylation of aryl iodides and aryl boronic acids with highly improved specific activity.

    PubMed

    van der Born, Dion; Sewing, Claudia; Herscheid, J Koos D M; Windhorst, Albert D; Orru, Romano V A; Vugts, Danielle J

    2014-10-01

    Herein, we describe a valuable method for the introduction of the [(18)F]CF3 group into arenes with highly improved specific activity by the reaction of [(18)F]trifluoromethane with aryl iodides or aryl boronic acids. This [(18)F]trifluoromethylation reaction is the first to be described in which the [(18)F]CF3 products are generated in actual trace amounts and can therefore effectively be used as PET tracers. The method shows broad scope with respect to possible aryl iodide and aryl boronic acid substrates, as well as good to excellent conversion. In particular, the [(18)F]trifluoromethylation of boronic acids was found to outperform [(18)F]trifluoromethylation reactions of halogenated aryl precursors with regard to conversion, reaction conditions, and kinetics. PMID:25155042

  3. A universal procedure for the [¹⁸F]trifluoromethylation of aryl iodides and aryl boronic acids with highly improved specific activity.

    PubMed

    van der Born, Dion; Sewing, Claudia; Herscheid, J Koos D M; Windhorst, Albert D; Orru, Romano V A; Vugts, Danielle J

    2014-10-01

    Herein, we describe a valuable method for the introduction of the [(18)F]CF3 group into arenes with highly improved specific activity by the reaction of [(18)F]trifluoromethane with aryl iodides or aryl boronic acids. This [(18)F]trifluoromethylation reaction is the first to be described in which the [(18)F]CF3 products are generated in actual trace amounts and can therefore effectively be used as PET tracers. The method shows broad scope with respect to possible aryl iodide and aryl boronic acid substrates, as well as good to excellent conversion. In particular, the [(18)F]trifluoromethylation of boronic acids was found to outperform [(18)F]trifluoromethylation reactions of halogenated aryl precursors with regard to conversion, reaction conditions, and kinetics.

  4. 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.

  5. 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.

  6. 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; 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. PMID:25051612

  7. 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; 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.

  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. 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.

  10. Bioinspired, releasable quorum sensing modulators.

    PubMed

    Gomes, José; Grunau, Alexander; Lawrence, Adrien K; Eberl, Leo; Gademann, Karl

    2013-01-01

    We demonstrate the synthesis and immobilization of natural product hybrids featuring an acyl-homoserine lactone and a nitrodopamine onto biocompatible TiO(2) surfaces through an operationally simple dip-and-rinse procedure. The resulting immobilized hybrids were shown to be powerful quorum sensing (QS) activators in Pseudomonas strains acting by slow release from the surface. PMID:23169441

  11. 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. PMID:27482994

  12. 14 CFR 1274.214 - Inquiries and release of information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGREEMENTS WITH COMMERCIAL FIRMS Pre-Award Requirements § 1274.214 Inquiries and release of information. NASA personnel shall follow the procedures established in NFS 1805.402 prior to releasing information to the...

  13. 14 CFR 1274.214 - Inquiries and release of information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGREEMENTS WITH COMMERCIAL FIRMS Pre-Award Requirements § 1274.214 Inquiries and release of information. NASA personnel shall follow the procedures established in NFS 1805.402 prior to releasing information to the...

  14. 14 CFR 1274.214 - Inquiries and release of information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGREEMENTS WITH COMMERCIAL FIRMS Pre-Award Requirements § 1274.214 Inquiries and release of information. NASA personnel shall follow the procedures established in NFS 1805.402 prior to releasing information to the...

  15. 14 CFR 1274.214 - Inquiries and release of information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGREEMENTS WITH COMMERCIAL FIRMS Pre-Award Requirements § 1274.214 Inquiries and release of information. NASA personnel shall follow the procedures established in NFS 1805.402 prior to releasing information to the...

  16. 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

  17. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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. 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.

  19. 24 CFR 58.76 - Procedure for objections.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Development ENVIRONMENTAL REVIEW PROCEDURES FOR ENTITIES ASSUMING HUD ENVIRONMENTAL RESPONSIBILITIES Release of Funds for Particular Projects § 58.76 Procedure for objections. A person or agency objecting to...

  20. 24 CFR 58.76 - Procedure for objections.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Development ENVIRONMENTAL REVIEW PROCEDURES FOR ENTITIES ASSUMING HUD ENVIRONMENTAL RESPONSIBILITIES Release of Funds for Particular Projects § 58.76 Procedure for objections. A person or agency objecting to...

  1. 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.

  2. 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.

  3. 32 CFR 93.5 - Procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SERVICE OF PROCESS; RELEASE OF OFFICIAL INFORMATION IN LITIGATION; AND TESTIMONY BY NSA PERSONNEL AS WITNESSES § 93.5 Procedures. (a) Release of official information in litigation. NSA personnel shall not..., but a record of such approval will be made and retained in the OGC. NSA personnel shall not...

  4. 32 CFR 93.5 - Procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SERVICE OF PROCESS; RELEASE OF OFFICIAL INFORMATION IN LITIGATION; AND TESTIMONY BY NSA PERSONNEL AS WITNESSES § 93.5 Procedures. (a) Release of official information in litigation. NSA personnel shall not..., but a record of such approval will be made and retained in the OGC. NSA personnel shall not...

  5. 28 CFR 527.31 - Procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... accordance with the provisions of 28 CFR part 524, subpart F. ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Procedures. 527.31 Section 527.31... be considered, particularly if release is within twelve months. (h) Release of inmates classified...

  6. Performance of Children With Developmental Dyslexia on Two Skill Learning Tasks-Serial Reaction Time and Tower of Hanoi Puzzle: A Test of the Specific Procedural Learning Difficulties Theory.

    PubMed

    Vakil, Eli; Lowe, Michal; Goldfus, Carol

    2015-01-01

    Among the various theories proposed to explain developmental dyslexia (DD), the theory of specific procedural learning difficulties has gained certain support and is the framework for the current research. This theory claims that an inability to achieve skill automaticity explains the difficulties experienced by individuals with DD. Previous research on automaticity and DD has exhibited methodological issues such as a failure to test a range of skills. The current study broadens previous findings by delineating various reading skills correlated with several aspects of skill acquisition. Furthermore, the study utilizes two nonverbal tasks that reflect distinct types of skills: Serial Reaction Time (SRT) and the Tower of Hanoi Puzzle (TOHP). A total of 53 children aged 11 to 13 participated in the study, of whom 23 were children with DD and 30 were controls. Participants completed a test battery that consisted of reading tests, the SRT, and the TOHP. Results show no differences in learning rate between individuals with or without DD, although individuals with DD performed both tasks at a slower rate. Correlations were identified between a number of reading measures and measures of skill acquisition, expressed primarily in individuals with DD. Implications are examined in the discussion. PMID:24153401

  7. CHANGING RELEASE CRITERIA FROM PAST TO PRESENT

    SciTech Connect

    Graf, A.; Valencia, L.

    2003-02-27

    Beginning with the decommissioning of nuclear power plants the release, criteria for radioactive materials has gained importance significantly. After decommissioning and dismantling, most of the residues need not be treated as radioactive waste, since they contain only small amounts of radioactivity. The Karlsruhe Research Center already dismantled two research reactors completely (the Karlstein Super Heated Steam Reactor and the Niederaichbach Nuclear Power Plant), while several additional decommissioning projects are currently in progress. About 70 % of the total waste mass within each project can be released from the area of atomic regulations and licenses. At the Niederaichbach and Karlstein sites the release procedures and the release criteria were determined in the decommissioning license, where issues such as controlling and release values were fixed. Additionally, each step of the release process has to be coordinated with the regulator. Today the general release criteria are contained in the atomic act. Depending on the nature of the material to be released (e.g. building structures or metallic waste), and depending on the further use of the material, such as unrestricted reuse or waste disposal, release values for each nuclide are established. To prepare the release of materials, a release plan including the release measurement results is sent to the regulator, who has to officially approve the concept.

  8. Validation of a simplified field-adapted procedure for routine determinations of methyl mercury at trace levels in natural water samples using species-specific isotope dilution mass spectrometry.

    PubMed

    Lambertsson, Lars; Björn, Erik

    2004-12-01

    A field-adapted procedure based on species-specific isotope dilution (SSID) methodology for trace-level determinations of methyl mercury (CH(3)Hg(+)) in mire, fresh and sea water samples was developed, validated and applied in a field study. In the field study, mire water samples were filtered, standardised volumetrically with isotopically enriched CH(3) (200)Hg(+), and frozen on dry ice. The samples were derivatised in the laboratory without further pre-treatment using sodium tetraethyl borate (NaB(C(2)H(5))(4)) and the ethylated methyl mercury was purge-trapped on Tenax columns. The analyte was thermo-desorbed onto a GC-ICP-MS system for analysis. Investigations preceding field application of the method showed that when using SSID, for all tested matrices, identical results were obtained between samples that were freeze-preserved or analysed unpreserved. For DOC-rich samples (mire water) additional experiments showed no difference in CH(3)Hg(+) concentration between samples that were derivatised without pre-treatment or after liquid extraction. Extractions of samples for matrix-analyte separation prior to derivatisation are therefore not necessary. No formation of CH(3)Hg(+) was observed during sample storage and treatment when spiking samples with (198)Hg(2+). Total uncertainty budgets for the field application of the method showed that for analyte concentrations higher than 1.5 pg g(-1) (as Hg) the relative expanded uncertainty (REU) was approximately 5% and dominated by the uncertainty in the isotope standard concentration. Below 0.5 pg g(-1) (as Hg), the REU was >10% and dominated by variations in the field blank. The uncertainty of the method is sufficiently low to accurately determine CH(3)Hg(+) concentrations at trace levels. The detection limit was determined to be 4 fg g(-1) (as Hg) based on replicate analyses of laboratory blanks. The described procedure is reliable, considerably faster and simplified compared to non-SSID methods and thereby very

  9. Mobile Energy Laboratory Procedures

    SciTech Connect

    Armstrong, P.R.; Batishko, C.R.; Dittmer, A.L.; Hadley, D.L.; Stoops, J.L.

    1993-09-01

    Pacific Northwest Laboratory (PNL) has been tasked to plan and implement a framework for measuring and analyzing the efficiency of on-site energy conversion, distribution, and end-use application on federal facilities as part of its overall technical support to the US Department of Energy (DOE) Federal Energy Management Program (FEMP). The Mobile Energy Laboratory (MEL) Procedures establish guidelines for specific activities performed by PNL staff. PNL provided sophisticated energy monitoring, auditing, and analysis equipment for on-site evaluation of energy use efficiency. Specially trained engineers and technicians were provided to conduct tests in a safe and efficient manner with the assistance of host facility staff and contractors. Reports were produced to describe test procedures, results, and suggested courses of action. These reports may be used to justify changes in operating procedures, maintenance efforts, system designs, or energy-using equipment. The MEL capabilities can subsequently be used to assess the results of energy conservation projects. These procedures recognize the need for centralized NM administration, test procedure development, operator training, and technical oversight. This need is evidenced by increasing requests fbr MEL use and the economies available by having trained, full-time MEL operators and near continuous MEL operation. DOE will assign new equipment and upgrade existing equipment as new capabilities are developed. The equipment and trained technicians will be made available to federal agencies that provide funding for the direct costs associated with MEL use.

  10. WHO expert committee on specifications for pharmaceutical preparations.

    PubMed

    2013-01-01

    The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: Release procedure for International Chemical Reference Substances; WHO guidelines on quality risk management; WHO guidelines on variations to a prequalified product; and the Collaborative procedure between the World Health Organization Prequalification of Medicines Programme and national medicines regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products.

  11. [76Br]BMK-152, a non-peptide analogue, with high affinity and low non-specific binding for the Corticotropin-Releasing Factor Type 1 Receptor (CRF1 receptor)

    PubMed Central

    Jagoda, Elaine M.; Lang, Lixin; McCullough, Karen; Contoreggi, Carlo; Kim, B. Moon; Ma, Ying; Rice, Kenner C.; Szajek, Lawrence P; Eckelman, William C.; Kiesewetter, Dale O.

    2013-01-01

    Corticotropin-releasing factor (CRF), a neuropeptide, regulates endocrine and autonomic responses to stress through G-protein coupled receptors, CRF1 or CRF2. A PET ligand able to monitor changes in CRF1 receptor occupancy in vivo would aid in understanding the pathophysiology of stress related diseases as well as in the clinical development of non-peptide antagonists with therapeutic value. We have radiolabeled the CRF1 receptor ligand, BMK-152 ([8-(4-bromo-2,6-dimethoxyphenyl)-2,7-dimethylpyrazolo[1,5-α][1,3,5]triazin-4-yl]-N,N-bis-(2-methoxyethyl)amine; ClogP= 2.6), at both the 3 and 4 position with [76Br]. Using in vitro autoradiography saturation studies the 4-[76Br]BMK-152 exhibited high affinity binding to both rat (Kd = 0.23 ± 0.07 nM; n=3) and monkey frontal cortex (Kd = 0.31 ± 0.08 nM; n=3) consistent with CRF1 receptor regional distribution whereas with the 3-[76Br]BMK-152, the Kd's could not be determined due to high non-specific binding. In vitro autoradiography competition studies using [125I]Tyr0-o-CRF confirmed that 3-Br-BMK-152 (Ki = 24.4 ± 4.9 nM; n=3) had lower affinity (70 fold) than 4-Br-BMK-152 (Ki = 0.35 ± 0.07 nM; n=3) in monkey frontal cortex and similiar studies using [125I]Sauvagine confirmed CRF1 receptor selectivity. In vivo studies with P-glycoprotein (PGP) knockout mice (KO) and their wildtype littermates (WT) showed that the brain uptake of 3-[76Br]BMK/4-[76Br]BMK was increased < 2 fold in KO vs WT indicating that 3-[76Br]BMK-152/4-[76Br]BMK was not a Pgp substrate. Rat brain uptakes of 4-[76Br] BMK-152 from ex vivo autoradiography studies showed regional localization consistent with known published CRF1 receptor distribution and potential as a PET ligand for in vivo imaging of CRF1 receptors. PMID:21308801

  12. Model Testing Using Data from Accidental Releases of 131I and 137Cs: 1: Model Testing Using Data on 131I Released from Hanford

    SciTech Connect

    Thiessen, Kathleen M.; Napier, Bruce A.; Filistovic, Vitold; Homma, Toshimitsu; Kanyar, Bela; Krajewski, Pawel; Kryshev, Alexander I.; Nedveckaite, Tatjana; Nenyei, Arpad; Sazykina, Tatiana G.; Tveten, Ulf; Sjoblom, Kirsti-Liisa; Robinson, Carol

    2002-09-01

    Two major areas of emphasis in the BIOMASS (Biosphere Modelling and Assessment Methods) programme were the improvement of the accuracy of model predictions and the improvement of modelling procedures within the general area of environmental assessment. Theme 2 of BIOMASS, Environmental Releases, focused specifically on issues of dose reconstruction and remediation assessment. Within Theme 2, the Dose Reconstruction Working Group was concerned with the evaluation of the reliability of methods and models used for dose reconstruction for specific individuals and members of specific population subgroups. The Dose Reconstruction Working Group of BIOMASS carried out model testing exercises. The present paper describes the first one, which was based on an accidental release of 131I from the Hanford Purex Chemical Separations Plant in the northwestern United States in September 1963 (BIOMASS, 1999). The scenario made use of monitoring data originally collected during the two months following the release (Soldat, 1965) and further evaluated as part of the Hanford Environmental Dose Reconstruction (HEDR) project in the 1990s (Farris et al., 1994). Radioiodine releases are important for many radiation accidents, and because data on the results of these releases are often incomplete, models for estimating 131I transport and exposure are essential in dose reconstruction efforts. The Hanford scenario therefore provided a valuable opportunity to intercompare modelling approaches and model predictions among several assessors, to compare model predictions with data, and to identify the most important sources of bias and uncertainty in the model results.

  13. Source Term Estimates of Radioxenon Released from the BaTek Medical Isotope Production Facility Using External Measured Air Concentrations

    SciTech Connect

    Eslinger, Paul W.; Cameron, Ian M.; Dumais, Johannes R.; Imardjoko, Yudi; Marsoem, Pujadi; McIntyre, Justin I.; Miley, Harry S.; Stoehlker, Ulrich; Widodo, Susilo; Woods, Vincent T.

    2015-10-01

    Abstract Batan Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies 99mTc for use in medical procedures. Atmospheric releases of Xe-133 in the production process at BaTek are known to influence the measurements taken at the closest stations of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The xenon isotopes released from BaTek are the same as those produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analysts trying to decide whether a specific measurement result came from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84E13 Bq of Xe-133. Concentrations of Xe-133 in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88E13 Bq. The same optimization process yielded a release estimate of 1.70E13 Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10 percent of each other. Weekly release estimates of 1.8E13 Bq and a 40 percent facility operation rate yields a rough annual release estimate of 3.7E13 Bq of Xe-133. This value is consistent with previously published estimates of annual releases for this facility, which are based on measurements at three IMS stations. These multiple lines of evidence cross-validate the stack release estimates and the release estimates from atmospheric samplers.

  14. The Practicality of Targeted Prostate Biopsy Procedures on the Dominant Side of the Tumor Determined by Magnetic Resonance Imaging in Elderly Patients with High Serum Levels of Prostate-Specific Antigen

    PubMed Central

    Huh, Jung Sik; Kim, Bong Soo; Kim, Young Joo; Kim, Sung Dae

    2015-01-01

    Purpose To examine the possibility of reducing the number of cores per prostate biopsy in elderly patients with high levels of prostate-specific antigen (PSA) without significantly lowering the detection rate of prostate cancer. Materials and Methods Two hundreds sixteen men with PSA levels >20 ng/mL who underwent prostate biopsies from May 2009 to April 2013 were retrospectively reviewed. With the help of magnetic resonance imaging (MRI), the laterality of the dominant tumor burden in patients was determined. The results of targeted biopsies were compared with those of conventional biopsy procedures. Results The mean age and PSA level were 79.5 years and 81.3 ng/mL, respectively, and the overall diagnostic rate of sextant biopsies was 81.9% (177/216). MRI was able to show the tumor burden in 189 of the 216 patients. The detection rate of transrectal ultrasonography (TRUS)-guided targeted biopsies was 87.3% (165/189). Detection rates were comparable with conventional biopsies (81.9% [177/216]) (p=0.23). Of the 177 men in whom the results of the sextant biopsy were positive, 12 men (6.8%) with PSA levels <29 ng/mL did not have any cancer cells according to targeted biopsies. However, all other patients were diagnosed with prostate cancer using the abovementioned techniques. Conclusions We believe that TRUS-guided targeted biopsies of the prostate in elderly men with high PSA levels could reduce the number of unnecessary cores per biopsy. However, a risk of detection loss remains. Therefore, we recommend that at least a sextant biopsy should be performed, even in elderly patients, in order to detect prostate cancer. PMID:26770939

  15. Region-specific roles of the prelimbic cortex, the dorsal CA1, the ventral DG and ventral CA1 of the hippocampus in the fear return evoked by a sub-conditioning procedure in rats.

    PubMed

    Fu, Juan; Xing, Xiaoli; Han, Mengfi; Xu, Na; Piao, Chengji; Zhang, Yue; Zheng, Xigeng

    2016-02-01

    The return of learned fear is an important issue in anxiety disorder research since an analogous process may contribute to long-term fear maintenance or clinical relapse. A number of studies demonstrate that mPFC and hippocampus are important in the modulation of post-extinction re-expression of fear memory. However, the region-specific role of these structures in the fear return evoked by a sub-threshold conditioning (SC) is not known. In the present experiments, we first examined specific roles of the prelimbic cortex (PL), the dorsal hippocampus (DH, the dorsal CA1 area in particular), the ventral hippocampus (the ventral dentate gyrus (vDG) and the ventral CA1 area in particular) in this fear return process. Then we examined the role of connections between PL and vCA1 with this behavioral approach. Rats were subjected to five tone-shock pairings (1.0-mA shock) to induce conditioned fear (freezing), followed by three fear extinction sessions (25 tone-alone trials each session). After a post-test for extinction memory, some rats were retrained with the SC procedure to reinstate tone-evoked freezing. Rat groups were injected with low doses of the GABAA agonist muscimol to selectively inactivate PL, DH, vDG, or vCA1 120 min before the fear return test. A disconnection paradigm with ipsilateral or contralateral muscimol injection of the PL and the vCA1 was used to examine the role of this pathway in the fear return. We found that transient inactivation of these areas significantly impaired fear return (freezing): inactivation of the prelimbic cortex blocked SC-evoked fear return in particular but did not influence fear expression in general; inactivation of the DH area impaired fear return, but had no effect on the extinction retrieval process; both ventral DG and ventral CA1 are required for the return of extinguished fear whereas only ventral DG is required for the extinction retrieval. These findings suggest that PL, DH, vDG, and vCA1 all contribute to the fear

  16. Best practices for code release

    NASA Astrophysics Data System (ADS)

    Berriman, G. Bruce

    2016-01-01

    In this talk, I want to describe what I think are the best practices for releasing code and having it adopted by end users. Make sure your code is licensed, so users will know how the software can be used and modified, and place your code in a public repository that (and make sure that you follow institutional policies in doing this). Yet licensing and releasing code are not enough: the code must be organized and documented so users can understand what it does, what its limitations are, and how to build and use it. I will describe what I think are best practices in developing the content to support release, including tutorials, design documents, specifications of interfaces and so on. Much of what I have learned on based on ten years of experience in supporting releases of the Montage Image Mosaic Engine.

  17. Synapsins differentially control dopamine and serotonin release.

    PubMed

    Kile, Brian M; Guillot, Thomas S; Venton, B Jill; Wetsel, William C; Augustine, George J; Wightman, R Mark

    2010-07-21

    Synapsins are a family of synaptic vesicle proteins that are important for neurotransmitter release. Here we have used triple knock-out (TKO) mice lacking all three synapsin genes to determine the roles of synapsins in the release of two monoamine neurotransmitters, dopamine and serotonin. Serotonin release evoked by electrical stimulation was identical in substantia nigra pars reticulata slices prepared from TKO and wild-type mice. In contrast, release of dopamine in response to electrical stimulation was approximately doubled in striatum of TKO mice, both in vivo and in striatal slices, in comparison to wild-type controls. This was due to loss of synapsin III, because deletion of synapsin III alone was sufficient to increase dopamine release. Deletion of synapsins also increased the sensitivity of dopamine release to extracellular calcium ions. Although cocaine did not affect the release of serotonin from nigral tissue, this drug did enhance dopamine release. Cocaine-induced facilitation of dopamine release was a function of external calcium, an effect that was reduced in TKO mice. We conclude that synapsins play different roles in the control of release of dopamine and serotonin, with release of dopamine being negatively regulated by synapsins, specifically synapsin III, while serotonin release appears to be relatively independent of synapsins. These results provide further support for the concept that synapsin function in presynaptic terminals varies according to the neurotransmitter being released. PMID:20660258

  18. Standards of neurosurgical procedures.

    PubMed

    Steiger, H J

    2001-01-01

    Written specifications with regard to procedures performed, equipment used, and training of the involved personnel are widely used in the industry and aviation to guarantee constant quality. Similar systems are progressively being introduced to medicine. We have made an effort to standardize surgical procedures by introducing step-by-step guidelines and checklists. The current experience shows that a system of written standards is applicable to neurosurgery and that the use of checklists contributes to the prevention of forgetting essential details. Written standards and checklists are also a useful training tool within a university hospital and facilitate communication of essentials to the residents. Comparison with aviation suggests that standardization leads to a remarkable but nonetheless limited reduction of adverse incidents. PMID:11840739

  19. Reusable Release Mechanism

    NASA Technical Reports Server (NTRS)

    Bunker, J. W.; Ritchie, R. S.

    1984-01-01

    Slider release mechanism reusable. Bears heavy loads while latched, yet gives smooth release motion. Release effected by explosively driving perpendicular slider out of engagement with load-bearing shank. Device has potential industrial applications such as emergency release of lifting cables from helicopters, cranes and hoists.

  20. Carpal tunnel release complicated by necrotizing fasciitis.

    PubMed

    Greco, R J; Curtsinger, L J

    1993-06-01

    We report a 31-year-old diabetic woman who underwent carpal tunnel release for median nerve compression followed by a laparoscopic tubal ligation. The procedure was complicated by a severe postoperative necrotizing fasciitis infection of the carpal tunnel release incision. This has not been previously reported. The wound was poorly responsive to antibiotic therapy and serial wound debridements. Control of the woman's infection required total excision of the palmar skin and fascia. Complicating factors in this case included the woman's long history of insulin-dependent diabetes and a concomitant clean-contaminated procedure.

  1. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  2. Radioactive materials released from nuclear power plants

    SciTech Connect

    Tichler, J.; Benkovitz, C.

    1981-11-01

    Releases of radioactive materials in airborne and liquid effluents from commercial light water reactors during 1979 have been compiled and reported. Data on solid waste shipments as well as selected operating information have been included. This report supplements earlier annual reports issued by the former Atomic Energy Commission and the Nuclear Regulatory Commission. The 1979 release data are compared with previous year's releases in tabular form. Data covering specific radionuclides are summarized.

  3. Administrative Procedures for Small Institutions. Second Edition.

    ERIC Educational Resources Information Center

    Mathews, Keith W., Ed.

    This guide offers sample administrative procedures and policies that can be used by small colleges and universities to prepare or revise administrative procedures manuals. The sample procedures and policies offered here have been compiled from a review of many manuals from many different institutions, and vary from the general to the specific.…

  4. Procedures for Peer Review of Grant Applications

    ERIC Educational Resources Information Center

    US Department of Education, 2006

    2006-01-01

    This guide presents information on the procedures for peer review of grant applications. It begins with an overview of the review process for grant application submission and review. The review process includes: (1) pre-submission procedures that enable the Institute to plan for specific review sessions; (2) application processing procedures; (3)…

  5. Radiometric correction procedure study

    NASA Technical Reports Server (NTRS)

    Colby, C.; Sands, R.; Murphrey, S.

    1978-01-01

    A comparison of MSS radiometric processing techniques identified as a preferred radiometric processing technique a procedure which equalizes the mean and standard deviation of detector-specific histograms of uncalibrated scene data. Evaluation of MSS calibration data demonstrated that the relationship between detector responses is essentially linear over the range of intensities typically observed in MSS data, and that the calibration wedge data possess a high degree of temporal stability. An analysis of the preferred radiometric processing technique showed that it could be incorporated into the MDP-MSS system without a major redesign of the system, and with minimal impact on system throughput.

  6. 32 CFR 806.17 - Release and processing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... preparing and processing an Air Force FOIA appeal package. (2) Air Force host tenant relationships. The Air Force host base FOIA manager may log, process, and report FOIA requests for Air Force tenant units. In such cases, the host base FOIA office refers all recommended denials and “no records” appeals to...

  7. 49 CFR 701.6 - Release and processing procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... FOIA request. The FOIA also does not require that a new computer program be developed to extract the..., programming or a particular format would result in a significant expenditure of resources or interfere...

  8. 49 CFR 701.6 - Release and processing procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... FOIA request. The FOIA also does not require that a new computer program be developed to extract the..., programming or a particular format would result in a significant expenditure of resources or interfere...

  9. 49 CFR 701.6 - Release and processing procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... FOIA request. The FOIA also does not require that a new computer program be developed to extract the..., programming or a particular format would result in a significant expenditure of resources or interfere...

  10. 49 CFR 701.6 - Release and processing procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... FOIA request. The FOIA also does not require that a new computer program be developed to extract the..., programming or a particular format would result in a significant expenditure of resources or interfere...

  11. 49 CFR 701.6 - Release and processing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... FOIA request. The FOIA also does not require that a new computer program be developed to extract the..., programming or a particular format would result in a significant expenditure of resources or interfere...

  12. TMACS Test Procedure TP008: SACS Interface. Revision 5

    SciTech Connect

    Washburn, S.J.

    1994-05-31

    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 SACS Interface functions.

  13. 10 CFR 850.31 - Release criteria.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Release criteria. 850.31 Section 850.31 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.31 Release criteria. (a) The responsible employer must clean beryllium-contaminated equipment and other items to...

  14. 10 CFR 850.31 - Release criteria.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Release criteria. 850.31 Section 850.31 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.31 Release criteria. (a) The responsible employer must clean beryllium-contaminated equipment and other items to...

  15. 21 CFR 181.28 - Release agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PRIOR-SANCTIONED FOOD INGREDIENTS Specific Prior-Sanctioned Food Ingredients § 181.28 Release agents....

  16. 10 CFR 850.31 - Release criteria.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Release criteria. 850.31 Section 850.31 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.31 Release... the equipment or item and its future use and the nature of the beryllium contamination. (c)...

  17. 10 CFR 850.31 - Release criteria.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Release criteria. 850.31 Section 850.31 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.31 Release... the equipment or item and its future use and the nature of the beryllium contamination. (c)...

  18. 10 CFR 850.31 - Release criteria.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Release criteria. 850.31 Section 850.31 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.31 Release... the equipment or item and its future use and the nature of the beryllium contamination. (c)...

  19. Capture and release of cancer cells using electrospun etchable MnO2 nanofibers integrated in microchannels

    NASA Astrophysics Data System (ADS)

    Liu, Hui-qin; Yu, Xiao-lei; Cai, Bo; You, Su-jian; He, Zhao-bo; Huang, Qin-qin; Rao, Lang; Li, Sha-sha; Liu, Chang; Sun, Wei-wei; Liu, Wei; Guo, Shi-shang; Zhao, Xing-zhong

    2015-03-01

    This paper introduces a cancer cell capture/release microchip based on the self-sacrificed MnO2 nanofibers. Through electrospinning, lift-off and soft-lithography procedures, MnO2 nanofibers are tactfully fabricated in microchannels to implement enrichment and release of cancer cells in liquid samples. The MnO2 nanofiber net which mimics the extra cellular matrix can lead to high capture ability with the help of a cancer cell-specific antibody bio-conjugation. Subsequently, an effective and friendly release method is carried out by using low concentration of oxalic acid to dissolve the MnO2 nanofiber substrate while keeping high viability of those released cancer cells at the same time. It is conceivable that our microchip may have potentials in realizing biomedical analysis of circulating tumor cells for biological and clinical researches in oncology.

  20. Controlled release from recombinant polymers.

    PubMed

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-09-28

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

  1. Controlled Release from Recombinant Polymers

    PubMed Central

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

  2. Multiplexed programmable release of captured DNA.

    PubMed

    Kennedy-Darling, Julia; Holden, Matthew T; Shortreed, Michael R; Smith, Lloyd M

    2014-11-01

    Nucleic-acid hybridization is widely used for the specific capture of complementary sequences from complex samples. It is useful for both analytical methodologies, such as array hybridization (e.g. transcriptome analysis, genetic-variation analysis), and preparative strategies such as exome sequencing and sequence-specific proteome capture and analysis (PICh, HyCCAPP). It has not generally been possible to selectively elute particular captured subsequences, however, as the conditions employed for disruption of a duplex can lack the specificity needed to discriminate between different sequences. We show here that it is possible to bind and selectively release multiple sets of sequences by using toehold-mediated DNA branch migration. The strategy is illustrated for simple mixtures of oligonucleotides, for the sequence-specific capture and specific release of crosslinked yeast chromatin, and for the specific release of oligonucleotides hybridized to DNA microarrays. PMID:25157426

  3. Release of soluble elements from biochars derived from various biomass feedstocks.

    PubMed

    Wu, Hailu; Che, Xiaodong; Ding, Zhuhong; Hu, Xin; Creamer, Anne Elise; Chen, Hao; Gao, Bin

    2016-01-01

    Biochar as soil amendment can increase soil carbon (C) sequestration and mineral nutrients; however, some of its soluble elements may also be unintentionally released during the application. In this work, eight types of biochars were derived from herbaceous, woody, and waste (tailing, manure, sludge) biomass feedstocks through slow pyrolysis at 600 °C in N2. The elemental composition, specific surface area, morphology, crystalline phases, thermal stability, surface functional groups, and pH of the point of zero charge of the biochars were determined using various methods. These properties varied significantly among the tested biochars, suggesting that feedstock type played an important role in controlling their properties. Laboratory release and toxicity characteristic leaching procedure extraction experiments were conducted to evaluate the potential release of nutritious and toxic element from biochars. Results showed that all the biochars released nutritious elements and thus, may be beneficial to plants when amended in soils. In general, biochars produced from herbaceous and woody biomass feedstocks showed low risks of releasing toxic elements. Biochar derived from sludge, however, might present ecotoxicological challenges for its environmental applications due to the release of toxic elements, such as heavy metals.

  4. Impact of the nonvolatile wine matrix composition on the in vivo aroma release from wines.

    PubMed

    Muñoz-González, Carolina; Martín-Álvarez, Pedro J; Moreno-Arribas, M Victoria; Pozo-Bayón, M Ángeles

    2014-01-01

    The impact of the nonvolatile wine matrix composition on the retronasal aroma release of four volatile compounds added to different types of wines has been evaluated. For this purpose, a tailor-made retronasal aroma trapping device (RATD) was used to entrap the exhaled breath of six panelists previously trained in a specific consumption procedure. Five wines of different composition (white wine, sparkling white wine, young red wine, aged red wine, and a sweet wine) were evaluated. Prior to the evaluation, with the exception of the sweet wine, the wines were adjusted to the same ethanol content and aromatized with a mixture of four target volatile compounds. Aroma release data were submitted to multivariate statistical analysis in order to relate wine chemical composition and aroma release during wine drinking. Results showed interindividual differences and a clustering of panelists among lower and higher aroma releasers, which was in agreement to the differences in their breathing capacity. A significant influence of the matrix composition in the low aroma releasers group during wine consumption was observed. The consumption of red wines provoked a significantly higher aroma release than the consumption of white and sweet wines. From the chemical composition determined in the wine samples (pH, total acidity, total polyphenols, neutral polysaccharides, residual sugar, and nitrogenous compounds), the amount of total polyphenols was better correlated with the observed effect.

  5. 14 CFR 34.81 - Fuel specifications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... EXHAUST EMISSION REQUIREMENTS FOR TURBINE ENGINE POWERED AIRPLANES Test Procedures for Engine Smoke Emissions (Aircraft Gas Turbine Engines) § 34.81 Fuel specifications. Fuel having specifications as...

  6. 14 CFR 34.81 - Fuel specifications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... EXHAUST EMISSION REQUIREMENTS FOR TURBINE ENGINE POWERED AIRPLANES Test Procedures for Engine Smoke Emissions (Aircraft Gas Turbine Engines) § 34.81 Fuel specifications. Fuel having specifications as...

  7. Intensity of activation and timing of deactivation modulate elastic energy storage and release in a pennate muscle and account for gait-specific initiation of limb protraction in the horse.

    PubMed

    Lichtwark, Glen A; Watson, Johanna C; Mavrommatis, Sophia; Wilson, Alan M

    2009-08-01

    The equine biceps brachii (biceps) initiates rapid limb protraction through a catapult mechanism. Elastic strain energy is slowly stored in an internal tendon and is then rapidly released to protract the forelimb. The muscle fibres are short, have little scope for length change and can therefore only shorten slowly compared with the speed at which the whole muscle must shorten, which makes them poor candidates for driving rapid limb protraction. We suggest that the muscle fibres in the biceps act to modulate the elastic energy output of the muscle-tendon unit (MTU) to meet the demands of locomotion under different conditions. We hypothesise that more elastic strain energy is stored and released from the biceps MTU during higher speed locomotion to accommodate the increase in energy required to protract the limb and that this can be achieved by varying the length change and activation conditions of the muscle. We examined the work performed by the biceps during trot and canter using an inverse dynamics analysis (IDA). We then used excised biceps muscles to determine how much work could be performed by the muscle in active and passive stretch-shorten cycles. A muscle model was developed to investigate the influence of changes in activation parameters on energy storage and energy return from the biceps MTU. Increased biceps MTU length change and increased work performed by the biceps MTU were found at canter compared with at trot. More work was performed by the ex vivo biceps MTU following activation of the muscle and by increasing muscle length change. However, the ratio of active to passive work diminished with increasing length change. The muscle model demonstrated that duration and timing of activation during stretch-shorten cycles could modulate the elastic energy storage and return from the biceps. We conclude that the equine biceps MTU acts as a tuneable spring and the contractile component functions to modulate the energy required for rapid forelimb

  8. Groundwater technical procedures of the U.S. Geological Survey

    USGS Publications Warehouse

    Cunningham, William L.; Schalk, Charles W.

    2011-01-01

    A series of groundwater technical procedures documents (GWPDs) has been released by the U.S. Geological Survey, Water-Resources Discipline, for general use by the public. These technical procedures were written in response to the need for standardized technical procedures of many aspects of groundwater science, including site and measuring-point establishment, measurement of water levels, and measurement of well discharge. The techniques are described in the GWPDs in concise language and are accompanied by necessary figures and tables derived from cited manuals, reports, and other documents. Because a goal of this series of procedures is to remain current with the state of the science, and because procedures change over time, this report is released in an online format only. As new procedures are developed and released, they will be linked to this document.

  9. 24 CFR 58.70 - Notice of intent to request release of funds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Housing and Urban Development ENVIRONMENTAL REVIEW PROCEDURES FOR ENTITIES ASSUMING HUD ENVIRONMENTAL RESPONSIBILITIES Release of Funds for Particular Projects § 58.70 Notice of intent to request release of funds....

  10. 24 CFR 58.70 - Notice of intent to request release of funds.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Housing and Urban Development ENVIRONMENTAL REVIEW PROCEDURES FOR ENTITIES ASSUMING HUD ENVIRONMENTAL RESPONSIBILITIES Release of Funds for Particular Projects § 58.70 Notice of intent to request release of funds....

  11. ELECTROMAGNETIC RELEASE MECHANISM

    DOEpatents

    Michelson, C.

    1960-09-13

    An electromagnetic release mechanism is offered that may be used, for example, for supporting a safety rod for a nuclear reactor. The release mechanism is designed to have a large excess holding force and a rapid, uniform, and dependable release. The fast release is accomplished by providing the electromagnet with slotttd polts separated by an insulating potting resin, and by constructing the poles with a ferro-nickel alloy. The combination of these two features materially reduces the eddy current power density whenever the magnetic field changes during a release operation. In addition to these features, the design of the armature is such as to provide ready entrance of fluid into any void that might tend to form during release of the armature. This also improves the release time for the mechanism. The large holding force for the mechanism is accomplished by providing a small, selected, uniform air gap between the inner pole piece and the armature.

  12. HUMAN RELIABILITY ANALYSIS FOR COMPUTERIZED PROCEDURES

    SciTech Connect

    Ronald L. Boring; David I. Gertman; Katya Le Blanc

    2011-09-01

    This paper provides a characterization of human reliability analysis (HRA) issues for computerized procedures in nuclear power plant control rooms. It is beyond the scope of this paper to propose a new HRA approach or to recommend specific methods or refinements to those methods. Rather, this paper provides a review of HRA as applied to traditional paper-based procedures, followed by a discussion of what specific factors should additionally be considered in HRAs for computerized procedures. Performance shaping factors and failure modes unique to computerized procedures are highlighted. Since there is no definitive guide to HRA for paper-based procedures, this paper also serves to clarify the existing guidance on paper-based procedures before delving into the unique aspects of computerized procedures.

  13. Nanoparticle release from dental composites.

    PubMed

    Van Landuyt, K L; Hellack, B; Van Meerbeek, B; Peumans, M; Hoet, P; Wiemann, M; Kuhlbusch, T A J; Asbach, C

    2014-01-01

    Dental composites typically contain high amounts (up to 60 vol.%) of nanosized filler particles. There is a current concern that dental personnel (and patients) may inhale nanosized dust particles (<100 nm) during abrasive procedures to shape, finish or remove restorations but, so far, whether airborne nanoparticles are released has never been investigated. In this study, composite dust was analyzed in real work conditions. Exposure measurements of dust in a dental clinic revealed high peak concentrations of nanoparticles in the breathing zone of both dentist and patient, especially during aesthetic treatments or treatments of worn teeth with composite build-ups. Further laboratory assessment confirmed that all tested composites released very high concentrations of airborne particles in the nanorange (>10(6)cm(-3)). The median diameter of airborne composite dust varied between 38 and 70 nm. Electron microscopic and energy dispersive X-ray analysis confirmed that the airborne particles originated from the composite, and revealed that the dust particles consisted of filler particles or resin or both. Though composite dust exhibited no significant oxidative reactivity, more toxicological research is needed. To conclude, on manipulation with the bur, dental composites release high concentrations of nanoparticles that may enter deeply into the lungs.

  14. Multicomponent Implant Releasing Dexamethasone

    NASA Astrophysics Data System (ADS)

    Nikkola, L.; Vapalahti, K.; Ashammakhi, N.

    2008-02-01

    Several inflammatory conditions are usually treated with corticosteroids. There are various problems like side effects with traditional applications of steroids, e.g. topical, or systemic routes. Local drug delivery systems have been studied and developed to gain more efficient administration with fewer side effects. Earlier, we reported on developing Dexamethasone (DX) releasing biodegradable fibers. However, their drug release properties were not satisfactory in terms of onset of drug release. Thus, we assessed the development of multicomponent (MC) implant to enhance earlier drug release from such biodegradable fibers. Poly (lactide-co-glycolide) (PLGA) and 2 wt-% and 8 wt-% DX were compounded and extruded with twin-screw extruder to form of fibers. Some of the fibers were sterilized to obtain a change in drug release properties. Four different fiber classes were studied: 2 wt-%, 8 wt-%, sterilized 2 wt-%, and sterilized 8 wt-%. 3×4 different DX-releasing fibers were then heat-pressed to form one multicomponent rod. Half of the rods where sterilized. Drug release was measured from initial fibers and multicomponent rods using a UV/VIS spectrometer. Shear strength and changes in viscosity were also measured. Drug release studies showed that drug release commenced earlier from multicomponent rods than from component fibers. Drug release from multicomponent rods lasted from day 30 to day 70. The release period of sterilized rods extended from day 23 to day 57. When compared to the original component fibers, the drug release from MC rods commenced earlier. The initial shear strength of MC rods was 135 MPa and decreased to 105 MPa during four weeks of immersion in phosphate buffer solution. Accordingly, heat pressing has a positive effect on drug release. After four weeks in hydrolysis, no disintegration was observed.

  15. 19 CFR 143.44 - RLF procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... fees through the ACH (see 19 CFR 24.25) or any other method of electronic payment authorized by CBP. (c.... Line release (see 19 CFR, Part 142, Subpart D) or immediate delivery procedures may not be combined... is made under statement processing (see 19 CFR 24.25)....

  16. 19 CFR 143.44 - RLF procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... fees through the ACH (see 19 CFR 24.25) or any other method of electronic payment authorized by CBP. (c.... Line release (see 19 CFR, Part 142, Subpart D) or immediate delivery procedures may not be combined... is made under statement processing (see 19 CFR 24.25)....

  17. 19 CFR 143.44 - RLF procedure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... fees through the ACH (see 19 CFR 24.25) or any other method of electronic payment authorized by CBP. (c.... Line release (see 19 CFR, Part 142, Subpart D) or immediate delivery procedures may not be combined... is made under statement processing (see 19 CFR 24.25)....

  18. 19 CFR 143.44 - RLF procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... fees through the ACH (see 19 CFR 24.25) or any other method of electronic payment authorized by CBP. (c.... Line release (see 19 CFR, Part 142, Subpart D) or immediate delivery procedures may not be combined... is made under statement processing (see 19 CFR 24.25)....

  19. 19 CFR 143.44 - RLF procedure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... fees through the ACH (see 19 CFR 24.25) or any other method of electronic payment authorized by CBP. (c.... Line release (see 19 CFR, Part 142, Subpart D) or immediate delivery procedures may not be combined... is made under statement processing (see 19 CFR 24.25)....

  20. 32 CFR 97.6 - Procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Whether the disclosure, including release in camera, is appropriate under the rules of procedure governing... camera, is appropriate or necessary under the relevant substantive law concerning privilege; (5) Whether the disclosure, except when in camera and necessary to assert a claim of privilege, would...

  1. 32 CFR 97.6 - Procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Whether the disclosure, including release in camera, is appropriate under the rules of procedure governing... camera, is appropriate or necessary under the relevant substantive law concerning privilege; (5) Whether the disclosure, except when in camera and necessary to assert a claim of privilege, would...

  2. 32 CFR 97.6 - Procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) Whether the disclosure, including release in camera, is appropriate under the rules of procedure governing... camera, is appropriate or necessary under the relevant substantive law concerning privilege; (5) Whether the disclosure, except when in camera and necessary to assert a claim of privilege, would...

  3. 32 CFR 97.6 - Procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) Whether the disclosure, including release in camera, is appropriate under the rules of procedure governing... camera, is appropriate or necessary under the relevant substantive law concerning privilege; (5) Whether the disclosure, except when in camera and necessary to assert a claim of privilege, would...

  4. 32 CFR 97.6 - Procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Whether the disclosure, including release in camera, is appropriate under the rules of procedure governing... camera, is appropriate or necessary under the relevant substantive law concerning privilege; (5) Whether the disclosure, except when in camera and necessary to assert a claim of privilege, would...

  5. 48 CFR 2942.1503 - Procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... with FOIA, as implemented by DOL under 29 CFR part 70. (2) Release of a contractor's performance... Section 2942.1503 Federal Acquisition Regulations System DEPARTMENT OF LABOR CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Contractor Performance Information 2942.1503 Procedures. (a) In accordance...

  6. 28 CFR 2.72 - Hearing procedure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Hearing procedure. 2.72 Section 2.72 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS District of Columbia Code: Prisoners and Parolees §...

  7. 14 CFR § 1274.214 - Inquiries and release of information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... information. NASA personnel shall follow the procedures established in NFS 1805.402 prior to releasing information to the news media or the general public. The procedures established by NFS 1805.403 shall...

  8. 24 CFR 58.73 - Objections to release of funds.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Urban Development ENVIRONMENTAL REVIEW PROCEDURES FOR ENTITIES ASSUMING HUD ENVIRONMENTAL RESPONSIBILITIES Release of Funds for Particular Projects § 58.73 Objections to release of funds. HUD (or the State) will not approve the ROF for any project before 15 calendar days have elapsed from the time of...

  9. 24 CFR 58.73 - Objections to release of funds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Urban Development ENVIRONMENTAL REVIEW PROCEDURES FOR ENTITIES ASSUMING HUD ENVIRONMENTAL RESPONSIBILITIES Release of Funds for Particular Projects § 58.73 Objections to release of funds. HUD (or the State) will not approve the ROF for any project before 15 calendar days have elapsed from the time of...

  10. 32 CFR 516.44 - Determination of release authorization.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... with DA policy governing the release of official documents in § 516.41(d) of this part. (2) Is the... disclosure appropriate under the rules of procedure governing the matter in which the request arose? (4... technical data withheld from public release pursuant to 32 CFR § 250, or other matters exempt...

  11. 32 CFR 516.44 - Determination of release authorization.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... with DA policy governing the release of official documents in § 516.41(d) of this part. (2) Is the... disclosure appropriate under the rules of procedure governing the matter in which the request arose? (4... technical data withheld from public release pursuant to 32 CFR § 250, or other matters exempt...

  12. 32 CFR 516.44 - Determination of release authorization.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... with DA policy governing the release of official documents in § 516.41(d) of this part. (2) Is the... disclosure appropriate under the rules of procedure governing the matter in which the request arose? (4... technical data withheld from public release pursuant to 32 CFR § 250, or other matters exempt...

  13. 32 CFR 516.44 - Determination of release authorization.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... with DA policy governing the release of official documents in § 516.41(d) of this part. (2) Is the... disclosure appropriate under the rules of procedure governing the matter in which the request arose? (4... technical data withheld from public release pursuant to 32 CFR § 250, or other matters exempt...

  14. 32 CFR 516.44 - Determination of release authorization.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... with DA policy governing the release of official documents in § 516.41(d) of this part. (2) Is the... disclosure appropriate under the rules of procedure governing the matter in which the request arose? (4... technical data withheld from public release pursuant to 32 CFR § 250, or other matters exempt...

  15. Slow Release Of Reagent Chemicals From Gel Matrices

    NASA Technical Reports Server (NTRS)

    Debnam, William J.; Barber, Patrick G.; Coleman, James

    1988-01-01

    Procedure developed for slow release of reagent chemicals into solutions. Simple and inexpensive and not subject to failure of equipment. Use of toothpaste-type tube or pump dispenser conceivably provides more controlled technique for storage and dispensation of gel matrix. Possible uses include controlled, slow release of reagents in chemical reactions, crystal growth, space-flight experiments, and preformed gel medications from packets.

  16. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  17. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  18. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  19. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  20. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  1. 12 CFR 310.6 - Special procedures: Medical records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... PRIVACY ACT REGULATIONS § 310.6 Special procedures: Medical records. Medical records shall be disclosed on... information to a medical doctor named by the requesting individual for release of the patient....

  2. 12 CFR 310.6 - Special procedures: Medical records.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... PRIVACY ACT REGULATIONS § 310.6 Special procedures: Medical records. Medical records shall be disclosed on... information to a medical doctor named by the requesting individual for release of the patient....

  3. Open Versus Arthroscopic Tennis Elbow Release

    PubMed Central

    Leiter, Jeff; Clark, Tod; McRae, Sheila; Dubberley, James; MacDonald, Peter B.

    2016-01-01

    Objectives: The primary objective of this study was to determine if quality of life and function are different following arthroscopic versus open tennis elbow release surgery. Based on retrospective studies, both approaches have been found to be beneficial, but no prospective randomized comparison has been conducted to date. Methods: Following a minimum six-months of conservative treatment, seventy-one patients (>16 yrs old) were randomized intraoperatively to undergo either arthroscopic or open lateral release. Outcome measures were the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), a 5-question VAS Pain Scale, and grip strength. Study assessments took place pre-, and 6-week, 3-, 6-, and 12-months post-surgery. Comparisons between groups and within groups over time were conducted using repeated measures ANOVA. A minimal clinically significant difference for the DASH had been previously identified as 15 points, and was used to compare groups as well at 12-months post-operative (Beaton et al. 2001). Results: Fifteen women and 19 men underwent the open procedure with a mean age of 47.1 years (6.7) and 13 women and 21 men were in the arthroscopic group with a mean age of 45.0 (6.9). No pre-surgery differences were found between groups based on age, sex, DASH or VAS scores. Both groups demonstrated a significant improvement in subjective measures and grip strength by 12-months post-surgery, and no significant differences were found between groups at any time point. The DASH, our primary outcome, decreased from a mean (SD) of 47.5 (14.5) pre-surgery to 21.9 (21.8) at 12-months post-surgery in the Open group and from 52.7 (16.0) to 22.6 (21.1) in the Arthroscopic group. VAS-pain scores (%) decreased in the Open group from 62.5 (17.2) pre-operatively to 30.0 (26.5) at 12-months. In the arthroscopic group, scores decreased from 63.7 (15.9) to 26.2 (24.6). Grip strength (kg) increased on the affected side from 23.6 (14.9) to 29.3 (16.3) and 21.4 (15.4) to

  4. Decontamination and Management of Human Remains Following Incidents of Hazardous Chemical Release

    SciTech Connect

    Hauschild, Veronique; Watson, Annetta Paule; Bock, Robert Eldon

    2012-01-01

    Abstract Objective: To provide specific procedural guidance and resources for identification, assessment, control, and mitigation of compounds that may contaminate human remains resulting from chemical attack or release. Design: A detailed technical, policy, and regulatory review is summarized. Setting: Guidance is suitable for civilian or military settings where human remains potentially contaminated with hazardous chemicals may be present. Settings would include sites of transportation accidents, natural disasters, terrorist or military operations, mortuary affairs or medical examiner processing and decontamination points, and similar. Patients, Participants: While recommended procedures have not been validated with actual human remains, guidance has been developed from data characterizing controlled experiments with fabrics, materiel, and laboratory animals. Main Outcome Measure(s): Presentation of logic and specific procedures for remains management, protection and decontamination of mortuary affairs personnel, as well as decision criteria for determining when remains are sufficiently decontaminated so as to pose no chemical health hazard. Results: Established procedures and existing equipment/materiel available for decontamination and verification provide appropriate and reasonable means to mitigate chemical hazards from remains. Extensive characterization of issues related to remains decontamination indicates that supra-lethal concentrations of liquid chemical warfare agent VX may prove difficult to decontaminate and verify in a timely fashion. Specialized personnel can and should be called upon to assist with monitoring necessary to clear decontaminated remains for transport and processing. Conclusions: Once appropriate decontamination and verification have been accomplished, normal procedures for remains processing and transport to the decedent s family and the continental United States can be followed.

  5. Proline-Rich Tyrosine Kinase 2 Mediates Gonadotropin-Releasing Hormone Signaling to a Specific Extracellularly Regulated Kinase-Sensitive Transcriptional Locus in the Luteinizing Hormone β-Subunit Gene

    PubMed Central

    Maudsley, Stuart; Naor, Zvi; Bonfil, David; Davidson, Lindsay; Karali, Dimitra; Pawson, Adam J.; Larder, Rachel; Pope, Caroline; Nelson, Nancy; Millar, Robert P.; Brown, Pamela

    2007-01-01

    G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH β-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH β-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH β-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression. PMID:17327421

  6. Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation

    PubMed Central

    Zhang, Xiaoyan; Wang, Xiaofei; Zhong, Weitong; Ren, Xiaoqing; Sha, Xianyi; Fang, Xiaoling

    2016-01-01

    Since elevated expression of matrix metalloproteinase (MMP)-2 and MMP-9 is commonly observed in several malignant tumors, MMPs have been widely reported as key factors in the design of drug delivery systems. Several strategies have been proposed to develop MMPs-responsive nanoparticles to deliver chemotherapeutics to malignant solid tumors. A stimuli-responsive drug delivery system, which could be cleaved by MMPs, was proposed in this study. By inserting an MMP-2/9 cleavable oligopeptide GPVGLIGK-NH2 (GK8) as spacer between α-tocopherol succinate (α-TOS) and methoxy-polyethylene glycol molecular weight (MW 2000 Da) activated by N-hydroxysuccinimide (mPEG2K-NHS), mPEG2K-GK8-α-TOS (TGK) was synthesized as the primary ingredient for MMP-2/9-sensitive micelles composed of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and TGK (n:n =40:60, TGK micelles). mPEG2K-α-TOS (T2K) was similarly synthesized as nonsensitive control. The TGK micelles showed better stability than nonsensitive micelles composed of TPGS and T2K (n:n =40:60, T2K micelles) owing to the inserted peptide. Fluorescence resonance energy transfer results indicated that TGK micelles could be successfully cleaved by MMP-2/9. Effective drug release was demonstrated in the presence of collagenase type IV, a mixture of MMP-2 and MMP-9. Compared with nonsensitive micelles, docetaxel (DTX)-loaded TGK micelles showed a fold higher cellular uptake in HT1080 cells. While the half-maximal inhibitory concentration (IC50) of TGK and T2K micelles were similar (P>0.05) in MCF-7 cells (MMP-2/9 underexpression), the IC50 values of the aforementioned micelles were 0.064±0.006 and 0.122±0.009 μg/mL, respectively, in HT1080 cells (MMP-2/9 overexpression). The MMP-2/9-sensitive micelles also demonstrated desired tumor targeting and accumulation ability in vivo. The results of in vivo antitumor effect evaluation indicate that TGK micelles are potent against solid tumors while maintaining minimum systemic

  7. Anesthetic consideration for neurointerventional procedures.

    PubMed

    Joung, Kyung Woon; Yang, Ku Hyun; Shin, Won Jung; Song, Myung Hee; Ham, Kyungdon; Jung, Seung Chul; Lee, Deok Hee; Suh, Dae Chul

    2014-09-01

    Interventional neuroradiology (INR) has been a rapidly expanding and advancing clinical area during the past few decades. As the complexity and diversity of INR procedures increases, the demand for anesthesia also increases. Anesthesia for interventional neuroradiology is a challenge for the anesthesiologist due to the unfamiliar working environment which the anesthesiologist must consider, as well as the unique neuro-interventional components. This review provides an overview of the anesthetic options and specific consideration of the anesthesia requirements for each procedure. We also introduce the anesthetic management for interventional neuroradiology performed in our medical institution.

  8. Evaluation of three approaches to meniscal release.

    PubMed

    Austin, B; Montgomery, R D; Wright, J; Bellah, J R; Tonks, C

    2007-01-01

    Three approaches to medial meniscal release (MMR) were compared using 48 canine cadaver stifles. The approaches included a caudomedial arthrotomy approach, a blind stab incision based on anatomic landmarks, and an arthroscopic guided approach. The cranial cruciate ligament was intact in all specimens. The time required to perform the meniscal release and joint capsule closure was recorded, as well as completeness and location of the meniscal transection. Damage to the caudal cruciate ligament, femoral cartilage, and medial collateral ligament were recorded. The mini-arthrotomy was 81% successful in accomplishment of MMR with a 4% rate of iatrogenic damage. The blind technique was 56% successful in the accomplishment of MMR with a 4% rate of iatrogenic damage. The arthroscopic guided approach was 62.5% successful in accomplishment of MMR, with a 10% rate of iatrogenic damage. Accomplishment and iatrogenic damage rates were not significantly different among procedures (p > 0.05). Significantly less time was required to perform the blind technique, and significantly greater time was required to perform the arthroscopic guided technique (p > 0.05). Significant differences were not noted among the procedures regarding the ability to accomplish the meniscal release or damage surrounding structures. None of the evaluated approaches for meniscal release resulted in a complete and accurate meniscal release for over 81% of the time.

  9. On the role of subsecond dopamine release in conditioned avoidance.

    PubMed

    Oleson, Erik B; Cheer, Joseph F

    2013-01-01

    Using shock avoidance procedures to study conditioned behavioral responses has a rich history within the field of experimental psychology. Such experiments led to the formulation of the general concept of negative reinforcement and specific theories attempting to explain escape and avoidance behavior, or why animals choose to either terminate or prevent the presentation of an aversive event. For example, the two-factor theory of avoidance holds that cues preceding an aversive event begin to evoke conditioned fear responses, and these conditioned fear responses reinforce the instrumental avoidance response. Current neuroscientific advances are providing new perspectives into this historical literature. Due to its well-established role in reinforcement processes and behavioral control, the mesolimbic dopamine system presented itself as a logical starting point in the search for neural correlates of avoidance and escape behavior. We recently demonstrated that phasic dopamine release events are inhibited by stimuli associated with aversive events but increased by stimuli preceding the successful avoidance of the aversive event. The latter observation is inconsistent with the second component of the two-factor theory of avoidance and; therefore, led us propose a new theoretical explanation of conditioned avoidance: (1) fear is initially conditioned to the warning signal and dopamine computes this fear association as a decrease in release, (2) the warning signal, now capable of producing a negative emotional state, suppresses dopamine release and behavior, (3) over repeated trials the warning signal becomes associated with safety rather than fear; dopaminergic neurons already compute safety as an increase in release and begin to encode the warning signal as the earliest predictor of safety (4) the warning signal now promotes conditioned avoidance via dopaminergic modulation of the brain's incentive-motivational circuitry.

  10. On the role of subsecond dopamine release in conditioned avoidance

    PubMed Central

    Oleson, Erik B.; Cheer, Joseph F.

    2013-01-01

    Using shock avoidance procedures to study conditioned behavioral responses has a rich history within the field of experimental psychology. Such experiments led to the formulation of the general concept of negative reinforcement and specific theories attempting to explain escape and avoidance behavior, or why animals choose to either terminate or prevent the presentation of an aversive event. For example, the two-factor theory of avoidance holds that cues preceding an aversive event begin to evoke conditioned fear responses, and these conditioned fear responses reinforce the instrumental avoidance response. Current neuroscientific advances are providing new perspectives into this historical literature. Due to its well-established role in reinforcement processes and behavioral control, the mesolimbic dopamine system presented itself as a logical starting point in the search for neural correlates of avoidance and escape behavior. We recently demonstrated that phasic dopamine release events are inhibited by stimuli associated with aversive events but increased by stimuli preceding the successful avoidance of the aversive event. The latter observation is inconsistent with the second component of the two-factor theory of avoidance and; therefore, led us propose a new theoretical explanation of conditioned avoidance: (1) fear is initially conditioned to the warning signal and dopamine computes this fear association as a decrease in release, (2) the warning signal, now capable of producing a negative emotional state, suppresses dopamine release and behavior, (3) over repeated trials the warning signal becomes associated with safety rather than fear; dopaminergic neurons already compute safety as an increase in release and begin to encode the warning signal as the earliest predictor of safety (4) the warning signal now promotes conditioned avoidance via dopaminergic modulation of the brain's incentive-motivational circuitry. PMID:23759871

  11. Statistical considerations in setting product specifications.

    PubMed

    Dong, Xiaoyu; Tsong, Yi; Shen, Meiyu

    2015-01-01

    According to ICH Q6A (1999), a specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. For drug products, specifications usually consist of test methods and acceptance criteria for assay, impurities, pH, dissolution, moisture, and microbial limits, depending on the dosage forms. They are usually proposed by the manufacturers and subject to the regulatory approval for use. When the acceptance criteria in product specifications cannot be pre-defined based on prior knowledge, the conventional approach is to use data from a limited number of clinical batches during the clinical development phases. Often in time, such acceptance criterion is set as an interval bounded by the sample mean plus and minus two to four standard deviations. This interval may be revised with the accumulated data collected from released batches after drug approval. In this article, we describe and discuss the statistical issues of commonly used approaches in setting or revising specifications (usually tighten the limits), including reference interval, (Min, Max) method, tolerance interval, and confidence limit of percentiles. We also compare their performance in terms of the interval width and the intended coverage. Based on our study results and review experiences, we make some recommendations on how to select the appropriate statistical methods in setting product specifications to better ensure the product quality.

  12. Intracellular sphingosine releases calcium from lysosomes.

    PubMed

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-11-27

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

  13. Gas release and conductivity modification studies

    NASA Technical Reports Server (NTRS)

    Linson, L. M.; Baxter, D. C.

    1979-01-01

    The behavior of gas clouds produced by releases from orbital velocity in either a point release or venting mode is described by the modification of snowplow equations valid in an intermediate altitude regime. Quantitative estimates are produced for the time dependence of the radius of the cloud, the average internal energy, the translational velocity, and the distance traveled. The dependence of these quantities on the assumed density profile, the internal energy of the gas, and the ratio of specific heats is examined. The new feature is the inclusion of the effect of the large orbital velocity. The resulting gas cloud models are used to calculate the characteristics of the field line integrated Pedersen conductivity enhancements that would be produced by the release of barium thermite at orbital velocity in either the point release or venting modes as a function of release altitude and chemical payload weight.

  14. How fit are children and adolescents with haemophilia in Germany? Results of a prospective study assessing the sport-specific motor performance by means of modern test procedures of sports science.

    PubMed

    Seuser, A; Boehm, P; Ochs, S; Trunz-Carlisi, E; Halimeh, S; Klamroth, R

    2015-07-01

    There are a lot of publications on the physical fitness of patients with haemophilia (PWH), however, most studies only reflect individual sport-specific motor capacities or focus on a single fitness ability. They involve small patient populations. In this respect principal objective of this study was to compare the physical fitness in all respects and the body composition of young PWH to healthy peers based on the most valid data we could get. Twenty-one German haemophilia treatment centres were visited from 2002 to 2009. PWH between 8 and 25 years were included. They performed a five-stage fitness test covering the sport-specific motor capacities for coordination, measured by one leg stand, strength, aerobic fitness and mobility as well as body composition. The patients' results were compared with age- and gender-specific reference values of healthy subjects. Two hundred and eighty-five PWH (mean age 13.2 ± 4.5 years, 164 PWH with severe disease) were included prospectively in the study. PWH are significantly below the reference values of healthy subjects in the one-leg stand test, the mobility of the lower extremity, the strength ratio of chest and back muscles and the endurance test. In body composition, the back strength and the mobility of the upper extremity PWH are significantly above the reference values. There are no significant differences in abdominal strength. In conclusion we found specific differences in different fitness abilities between PWH and healthy subjects. Knowing this, we are able to work out exercise programmes to compensate the diminished fitness abilities for our PWH.

  15. 28 CFR 2.50 - Revocation hearing procedure.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Revocation hearing procedure. 2.50 Section 2.50 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... whether the parolee has violated the conditions of his release and, if so, whether his parole or...

  16. Computerized procedures system

    DOEpatents

    Lipner, Melvin H.; Mundy, Roger A.; Franusich, Michael D.

    2010-10-12

    An online data driven computerized procedures system that guides an operator through a complex process facility's operating procedures. The system monitors plant data, processes the data and then, based upon this processing, presents the status of the current procedure step and/or substep to the operator. The system supports multiple users and a single procedure definition supports several interface formats that can be tailored to the individual user. Layered security controls access privileges and revisions are version controlled. The procedures run on a server that is platform independent of the user workstations that the server interfaces with and the user interface supports diverse procedural views.

  17. Deconvolution procedure of the UV-vis spectra. A powerful tool for the estimation of the binding of a model drug to specific solubilisation loci of bio-compatible aqueous surfactant-forming micelle.

    PubMed

    Calabrese, Ilaria; Merli, Marcello; Turco Liveri, Maria Liria

    2015-05-01

    UV-vis-spectra evolution of Nile Red loaded into Tween 20 micelles with pH and [Tween 20] have been analysed in a non-conventional manner by exploiting the deconvolution method. The number of buried sub-bands has been found to depend on both pH and bio-surfactant concentration, whose positions have been associated to Nile Red confined in aqueous solution and in the three micellar solubilisation sites. For the first time, by using an extended classical two-pseudo-phases-model, the robust treatment of the spectrophotometric data allows the estimation of Nile Red binding constant to the available loci. Hosting capability towards Nile Red is exalted by the pH enhancement. Comparison between binding constant values classically evaluated and those estimated by the deconvolution protocol unveiled that overall binding values perfectly match with the mean values of the local binding sites. This result suggests that deconvolution procedure provides more precise and reliable values, which are more representative of drug confinement. PMID:25703359

  18. Large scientific releases

    SciTech Connect

    Pongratz, M.B.

    1981-01-01

    The motivation for active experiments in space is considered, taking into account the use of active techniques to obtain a better understanding of the natural space environment, the utilization of the advantages of space as a laboratory to study fundamental plasma physics, and the employment of active techniques to determine the magnitude, degree, and consequences of artificial modification of the space environment. It is pointed out that mass-injection experiments in space plasmas began about twenty years ago with the Project Firefly releases. Attention is given to mass-release techniques and diagnostics, operational aspects of mass release active experiments, the active observation of mass release experiments, active perturbation mass release experiments, simulating an artificial modification of the space environment, and active experiments to study fundamental plasma physics.

  19. Masking Release for Igbo and English

    PubMed Central

    Ebem, Deborah U.; Desloge, Joseph G.; Reed, Charlotte M.; Braida, Louis D.; Uguru, Joy O.

    2014-01-01

    In this research, we explored the effect of noise interruption rate on speech intelligibility. Specifically, we used the Hearing In Noise Test (HINT) procedure with the original HINT stimuli (English) and Igbo stimuli to assess speech reception ability in interrupted noise. For a given noise level, the HINT test provides an estimate of the signal-to-noise ratio (SNR) required for 50%-correct speech intelligibility. The SNR for 50%-correct intelligibility changes depending upon the interruption rate of the noise. This phenomenon (called Masking Release) has been studied extensively in English but not for Igbo – which is an African tonal language spoken predominantly in South Eastern Nigeria. This experiment explored and compared the phenomenon of Masking Release for (i) native English speakers listening to English, (ii) native Igbo speakers listening to English, and (iii) native Igbo speakers listening to Igbo. Since Igbo is a tonal language and English is a non-tonal language, this allowed us to compare Masking Release patterns on native speakers of tonal and non-tonal languages. Our results for native English speakers listening to English HINT show that the SNR and the masking release are orderly and consistent with other English HINT data for English speakers. Our result for Igbo speakers listening to English HINT sentences show that there is greater variability in results across the different Igbo listeners than across the English listeners. This result likely reflects different levels of ability in the English language across the Igbo listeners. The masking release values in dB are less than for English listeners. Our results for Igbo speakers listening to Igbo show that in general, the SNRs for Igbo sentences are lower than for English/English and Igbo/English. This means that the Igbo listeners could understand 50% of the Igbo sentences at SNRs less than those required for English sentences by either native or non-native listeners. This result can be

  20. Radioactive materials released from nuclear power plants

    SciTech Connect

    Tichler, J.; Norden, K.; Congemi, J. )

    1989-10-01

    Releases of radioactive materials in airborne and liquid effluents from commercial light water reactors during 1987 have been compiled and reported. Data on solid waste shipments as well as selected operating information have been included. This report supplements earlier annual reports issued by the former Atomic Energy Commission and the Nuclear Regulatory Commission. The 1987 release data are summarized in tabular form. Data covering specific radionuclides are summarized. 16 tabs.

  1. Radioactive materials released from nuclear power plants

    SciTech Connect

    Tichler, J.; Norden, K.; Congemi, J. )

    1991-05-01

    Releases of radioactive materials in airborne and liquid effluents from commercial light water reactors during 1988 have been compiled and reported. Data on solid waste shipments as well as selected operating information have been included. This report supplements earlier annual reports issued by the former Atomic Energy Commission and the Nuclear Regulatory Commission. The 1988 release data are summarized in tabular form. Data covering specific radionuclides are summarized. 16 tabs.

  2. Cognitive procedural learning in amnesia.

    PubMed

    Schmidtke, K; Handschu, R; Vollmer, H

    1996-12-01

    This group study examined the role of residual declarative memory and task-specific cognitive abilities for cognitive procedural learning in amnesia. 20 amnesic patients and 40 control subjects were studied, using four new cognitive tasks, as well as the Tower of Hanoi and a Mirror Reading task. On the cognitive tasks, but not on Mirror Reading, the learning of amnesic patients was significantly impaired relative to controls. Between- and within-group differences in learning were found to be statistically related to cognitive abilities that are involved in the processing of the procedural tasks. In amnesic patients, significant effects of residual declarative memory on learning scores were not observed, but there was indirect evidence for a role of memory in two tasks. The analysis of the correlative relationship between absolute procedural task performances and cognitive abilities indicated a prolonged dependence on nonspecific intellectual abilities in amnesic patients, suggesting a retarded transition to more advanced stages of skill acquisition.

  3. 40 CFR 1066.10 - Other procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....10 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS... CFR 1065.10(c). All the test procedures noted as exceptions to the specified procedures are considered... specific meanings; “special procedures” are those allowed by 40 CFR 1065.10(c)(2) and “alternate...

  4. 40 CFR 1066.10 - Other procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....10 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS... CFR 1065.10(c). All the test procedures noted as exceptions to the specified procedures are considered... specific meanings; “special procedures” are those allowed by 40 CFR 1065.10(c)(2) and “alternate...

  5. Fire Service Training. Firefighting Procedures. (Revised).

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Community Colleges, Raleigh.

    One of a set of fourteen instructional outlines for use in a course to train novice firemen, this guide covers firefighting procedures and principles. Emphasis is placed on pre-fire planning, the techniques for applying a plan to a course of action, and the selection of proper fire fighting procedures to meet specific needs. Besides the methods of…

  6. 40 CFR 1507.3 - Agency procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Agency procedures. 1507.3 Section 1507.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY AGENCY COMPLIANCE § 1507.3 Agency... environmental impact statements. (c) Agency procedures may include specific criteria for providing...

  7. 40 CFR 1507.3 - Agency procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Agency procedures. 1507.3 Section 1507.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY AGENCY COMPLIANCE § 1507.3 Agency... environmental impact statements. (c) Agency procedures may include specific criteria for providing...

  8. 40 CFR 1507.3 - Agency procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Agency procedures. 1507.3 Section 1507.3 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY AGENCY COMPLIANCE § 1507.3 Agency... environmental impact statements. (c) Agency procedures may include specific criteria for providing...

  9. Student Loan Collection Procedures. Revised Edition.

    ERIC Educational Resources Information Center

    McAlvey, Warren C.; Price, Anne J.

    Guidelines for loan collection staff who award/service college student loans are presented. Attention is directed to sound collection procedures, three specific loan programs, suing a defaulted borrower, the Family Educational Rights and Privacy Act and the use of credit bureaus, and student loan borrower bankruptcy. Loan collection procedures for…

  10. Commensalism in Teaching: Parliamentary Procedure and Argumentation.

    ERIC Educational Resources Information Center

    Botan, Carl H.; Ziegelmueller, George W.

    Parliamentary procedure might best be taught in a context specific format; it would be better understood by students if not taught as a "stand alone" subject. Since the basic concepts of argumentation theory--propositions, stasis, and presumption and burden of proof--are reinforced by the rules of parliamentary procedure, instructors can teach…

  11. Void fraction instrument acceptance test procedure

    SciTech Connect

    Pearce, K.L.

    1994-09-15

    This acceptance test procedure (ATP) was written to test the void fraction instrument (VFI) and verify that the unit is ready for field service. The procedure verifies that the mechanical and electrical features (not specifically addressed in the software ATP) and software alarms are operating as designed.

  12. Morphology of Gas Release in Physical Simulants

    SciTech Connect

    Daniel, Richard C.; Burns, Carolyn A.; Crawford, Amanda D.; Hylden, Laura R.; Bryan, Samuel A.; MacFarlan, Paul J.; Gauglitz, Phillip A.

    2014-07-03

    This report documents testing activities conducted as part of the Deep Sludge Gas Release Event Project (DSGREP). The testing described in this report focused on evaluating the potential retention and release mechanisms of hydrogen bubbles in underground radioactive waste storage tanks at Hanford. The goal of the testing was to evaluate the rate, extent, and morphology of gas release events in simulant materials. Previous, undocumented scoping tests have evidenced dramatically different gas release behavior from simulants with similar physical properties. Specifically, previous gas release tests have evaluated the extent of release of 30 Pa kaolin and 30 Pa bentonite clay slurries. While both materials are clays and both have equivalent material shear strength using a shear vane, it was found that upon stirring, gas was released immediately and completely from bentonite clay slurry while little if any gas was released from the kaolin slurry. The motivation for the current work is to replicate these tests in a controlled quality test environment and to evaluate the release behavior for another simulant used in DSGREP testing. Three simulant materials were evaluated: 1) a 30 Pa kaolin clay slurry, 2) a 30 Pa bentonite clay slurry, and 3) Rayleigh-Taylor (RT) Simulant (a simulant designed to support DSGREP RT instability testing. Entrained gas was generated in these simulant materials using two methods: 1) application of vacuum over about a 1-minute period to nucleate dissolved gas within the simulant and 2) addition of hydrogen peroxide to generate gas by peroxide decomposition in the simulants over about a 16-hour period. Bubble release was effected by vibrating the test material using an external vibrating table. When testing with hydrogen peroxide, gas release was also accomplished by stirring of the simulant.

  13. Controlling protein release using biodegradable microparticles

    NASA Astrophysics Data System (ADS)

    Kline, Benjamin Patrick

    Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

  14. A procedure for evaluating environmental impact

    USGS Publications Warehouse

    Leopold, Luna Bergere; Clarke, F.E.; Hanshaw, B.B.; Balsley, J.R.

    1971-01-01

    The procedure does not limit the development of detail in any specific aspect of the environment; a separate expanded matrix for any environmental aspect can easily be developed within the framework provided.

  15. Public Sector Impasse Procedures.

    ERIC Educational Resources Information Center

    Vadakin, James C.

    The subject of collective bargaining negotiation impasse procedures in the public sector, which includes public school systems, is a broad one. In this speech, the author introduces the various procedures, explains how they are used, and lists their advantages and disadvantages. Procedures discussed are mediation, fact-finding, arbitration,…

  16. 28 CFR 2.216 - Revocation hearing procedure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Revocation hearing procedure. 2.216....216 Revocation hearing procedure. (a) The purpose of the revocation hearing shall be to determine... the term should be revoked or the releasee restored to supervised release. (b) At a local...

  17. 28 CFR 2.103 - Revocation hearing procedure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Revocation hearing procedure. 2.103... Parolees § 2.103 Revocation hearing procedure. (a) The purpose of the revocation hearing shall be to... mandatory release should be revoked or reinstated. (b) At a local revocation hearing, the alleged...

  18. 22 CFR 215.6 - Special procedures: Medical records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Special procedures: Medical records. 215.6... PRIVACY ACT OF 1974 § 215.6 Special procedures: Medical records. If the Assistant Director for Administration or the Privacy Liaison Officer, determines that the release directly to the individual of...

  19. 22 CFR 215.6 - Special procedures: Medical records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Special procedures: Medical records. 215.6... PRIVACY ACT OF 1974 § 215.6 Special procedures: Medical records. If the Assistant Director for Administration or the Privacy Liaison Officer, determines that the release directly to the individual of...

  20. 22 CFR 215.6 - Special procedures: Medical records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Special procedures: Medical records. 215.6... PRIVACY ACT OF 1974 § 215.6 Special procedures: Medical records. If the Assistant Director for Administration or the Privacy Liaison Officer, determines that the release directly to the individual of...