WorldWideScience

Sample records for gp request forms

  1. Personal Information Request Form

    International Development Research Centre (IDRC) Digital Library (Canada)

    PC Forms Inc. 834-4048

    To apply for information under the Privacy Act, complete this form or a written request mentioning the Act. Describe the information being sought and provide any relevant details necessary to help the. International Development Research Centre. (IDRC) find it. If you require assistance, refer to. Info Source (Sources of ...

  2. 75 FR 28777 - Information Collection; Financial Information Security Request Form

    Science.gov (United States)

    2010-05-24

    ... Collection; Financial Information Security Request Form AGENCY: Forest Service, USDA. ACTION: Notice; Request... currently approved information collection; Financial Information Security Request Form. DATES: Comments must... Standard Time, Monday through Friday. SUPPLEMENTARY INFORMATION: Title: Financial Information Security...

  3. Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

    Science.gov (United States)

    d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

    2015-04-16

    ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. DownloadAccess to Information Request form

    International Development Research Centre (IDRC) Digital Library (Canada)

    PC Forms Inc. 834-4048

    To apply for information under the Access to. Information Act, complete this form or a written request mentioning the Act. Describe the information being sought and provide any relevant details necessary to help the International. Development Research Centre (IDRC) find it. If you require assistance, refer to Info Source.

  5. 19 CFR 177.25 - Form and content of request.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Form and content of request. 177.25 Section 177.25....25 Form and content of request. (a) A request for an advisory ruling shall be in writing and shall... for which a country-of-origin determination is requested; (3) The country or instrumentality an...

  6. TS/EL ELECTRICAL WORK REQUEST FORM

    CERN Multimedia

    TS Department

    2008-01-01

    To facilitate the processing of requests for minor electrical installation work to be carried out by the TS/EL group, a new procedure designed to improve contacts and exchange of information with customers has been set up. The procedure comprises a check to determine whether the TS/EL or the TS/FM group is responsible for the area where the electrical work is to be done. If the work is to be performed by the EL group, an on-line request form must be completed. The following steps must be completed: On a web browser, use the link http://ts-dep.web.cern.ch/ts-dep/groups/el/el.htm In the left-hand menu choose ‘Demande de Travaux Electriques’ Enter the building number to check which group to contact and click ‘FIND’ If the area is: Under FM’s responsibility:\tCall 77777 Under EL’s responsibility:\tClick the link to the work form, complete it and send it (click ‘ENVOYER’) IMPORTANT This form is for minor electrical installation requests only. Please call 72201 in t...

  7. Audit of Completion of Radiology Request Form in a Nigerian ...

    African Journals Online (AJOL)

    Background: Clinical audit is one approach to improve the quality of patient care, completion of request form inclusive. Radiology request forms are essential communication tools between the clinician and the radiologist. The aim of this study is to audit the adequacy of completion of X-ray request forms. Methodology: A ...

  8. 75 FR 33886 - Proposed Collection; Comment Request for Form 5308

    Science.gov (United States)

    2010-06-15

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 5308, Request for Change in Plan/Trust Year. DATES: Written comments should be received on or before... INFORMATION: Title: Request for Change in Plan/Trust Year. OMB Number: 1545-0201. Form Number: 5308. Abstract...

  9. 78 FR 24312 - Proposed Collection; Comment Request for Form 5308

    Science.gov (United States)

    2013-04-24

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 5308, Request for Change in Plan/Trust Year. DATES: Written comments should be received on or before... . SUPPLEMENTARY INFORMATION: Title: Request for Change in Plan/Trust Year. OMB Number: 1545-0201. Form Number...

  10. 78 FR 73819 - Information Collection; Financial Information Security Request Form

    Science.gov (United States)

    2013-12-09

    ... DEPARTMENT OF AGRICULTURE Forest Service Information Collection; Financial Information Security..., Financial Information Security Request Form. DATES: Comments must be received in writing on or before... Information Security Request Form. OMB Number: 0596-0204. Expiration Date of Approval: 02/28/2014. Type of...

  11. 78 FR 29205 - Proposed Collection; Comment Request for Form 4952

    Science.gov (United States)

    2013-05-17

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Form 4952 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY... 4952, Investment Interest Expense Deduction. DATES: Written comments should be received on or before...

  12. 78 FR 45616 - Proposed Collection; Comment Request for Form 8960

    Science.gov (United States)

    2013-07-29

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Form 8960 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY... 8960, Net Investment Income Tax-Individuals, Estates, and Trusts. DATES: Written comments should be...

  13. 75 FR 33380 - Proposed Collection; Comment Request for Form 4952

    Science.gov (United States)

    2010-06-11

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Form 4952 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY... 4952, Investment Interest Expense Deduction. DATES: Written comments should be received on or before...

  14. 78 FR 24814 - Proposed Collection; Comment Request for Form 8612

    Science.gov (United States)

    2013-04-26

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Form 8612 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY... 8612, Return of Excise Tax on Undistributed Income of Real Estate Investment Trusts. DATES: Written...

  15. 75 FR 33887 - Proposed Collection; Comment Request for Form 8612

    Science.gov (United States)

    2010-06-15

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Form 8612 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY... 8612, Return of Excise Tax on Undistributed Income of Real Estate Investment Trusts. DATES: Written...

  16. 44 CFR 6.30 - Form of requests.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Form of requests. 6.30 Section 6.30 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... manager, at his discretion, may accept oral requests for access subject to verification of identity. ...

  17. 77 FR 64379 - Proposed Collection; Comment Request for Form 1000

    Science.gov (United States)

    2012-10-19

    ... 1000 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY... 1000, Ownership Certificate. DATES: Written comments should be received on or before December 18, 2012...: Ownership Certificate. OMB Number: 1545-0054. Form Number: 1000. Abstract: Form 1000 is used by citizens...

  18. Multicentre Assessment of Radiology Request Form Completion in ...

    African Journals Online (AJOL)

    An important element in the multidisciplinary approach to patient management is communications among clinicians. As most of the patients attending any hospital have to go through the department of radiology, the pattern and attitude of clinicians to the completion of radiology request forms was assessed in three teaching ...

  19. 76 FR 40774 - Proposed Collection; Comment Request for Form 8621

    Science.gov (United States)

    2011-07-11

    ... 8621, Return by a Shareholder of a Passive Foreign Investment Company or Qualified Electing Fund. DATES... Passive Foreign Investment Company or Qualified Electing Fund. OMB Number: 1545-1002. Form Number: 8621... included in the request for OMB approval. All comments will become a matter of public record. Comments are...

  20. 78 FR 61448 - Proposed Collection; Comment Request for Form 8834

    Science.gov (United States)

    2013-10-03

    ... used to claim any qualified electric vehicle passive activity credit allowed for the current tax year... vehicle passive activity credit allowed for the current tax year. Changes to the form will decrease burden... will be summarized and/or included in the request for OMB approval. All comments will become a matter...

  1. 48 CFR 245.7101-4 - DD Form 1640, Request for Plant Clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1640, Request for Plant Clearance. 245.7101-4 Section 245.7101-4 Federal Acquisition Regulations System DEFENSE... Forms 245.7101-4 DD Form 1640, Request for Plant Clearance. Use to request plant clearance assistance or...

  2. 76 FR 47648 - Proposed Collection; Comment Request for Form 8850

    Science.gov (United States)

    2011-08-05

    ... 8850, Pre-Screening Notice and Certification Request for the Work Opportunity and Welfare-to-Work...: Pre-Screening Notice and Certification Request for the Work Opportunity and Welfare-to-Work Credits... request to a state employment security agency to certify an employee as a member of a targeted group for...

  3. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need for...

  4. 77 FR 47426 - Agency Information Collection Activities: Request for the Return of Original Documents, Form...

    Science.gov (United States)

    2012-08-08

    ...-0100] Agency Information Collection Activities: Request for the Return of Original Documents, Form.... (2) Title of the Form/Collection: Request for the Return of Original Documents. (3) Agency form... obtain original document(s) contained in an alien file. (5) An estimate of the total number of...

  5. 77 FR 65706 - Agency Information Collection Activities: Request for the Return of Original Documents, Form...

    Science.gov (United States)

    2012-10-30

    ...-0100] Agency Information Collection Activities: Request for the Return of Original Documents, Form... Collection. (2) Title of the Form/Collection: Request for the Return of Original Documents. (3) Agency form... obtain original document(s) contained in an alien file. (5) An estimate of the total number of...

  6. 21 CFR 203.60 - Request and receipt forms, reports, and records.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) DRUGS: GENERAL PRESCRIPTION DRUG MARKETING Request and Receipt Forms, Reports, and...; (2) Preserved in accessible and retrievable fashion; and (3) Available to permit copying for purposes...

  7. 75 FR 49026 - Proposed Collection; Comment Request for Form 8877

    Science.gov (United States)

    2010-08-12

    ... 8877, Request for Waiver of Annual Income Recertification Requirement for the Low-Income Housing Credit...- 6665, or through the Internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: Request for Waiver of Annual Income Recertification Requirement for the Low-Income Housing Credit. OMB Number...

  8. 78 FR 63564 - Proposed Collection; Comment Request for Form 8038-R

    Science.gov (United States)

    2013-10-24

    ... 8038-R AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 8038-R, Request for Recovery of Overpayments Under Arbitrage Rebate Provisions. DATES: Written... Rebate Provisions. OMB Number: 1545-1750. Form Number: 8038-R. Abstract: Under Treasury Regulations...

  9. 75 FR 61244 - Proposed Collection; Comment Request for Form 8038-R

    Science.gov (United States)

    2010-10-04

    ... 8038-R AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 8038-R, Request for Recovery of Overpayments Under Arbitrage Rebate Provisions. DATES: Written... information or copies of the form and instructions should be directed to R. Joseph Durbala at Internal Revenue...

  10. 78 FR 21500 - Proposed Collection; Comment Request for Form 8275 and 8275-R

    Science.gov (United States)

    2013-04-10

    ... 8275 and 8275-R AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for... Form 8275, Disclosure Statement, and Form 8275-R, Regulation Disclosure Statement. DATES: Written... (Form 8275) and Regulation Disclosure Statement (Form 8275-R). OMB Number: 1545-0889. Form Number: Forms...

  11. 76 FR 49836 - Proposed Collection; Comment Request for Form 8846

    Science.gov (United States)

    2011-08-11

    ... Actions: Lines 7 through 11 will be removed, since the passive activity limit and the carryover amounts... included in the request for OMB approval. All comments will become a matter of public record. Comments are...

  12. 77 FR 6863 - Proposed Collection; Comment Request for VITA/TCE Program Forms

    Science.gov (United States)

    2012-02-09

    .../TCE Program Forms AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for... VITA/TCE Program Forms 14310, 8653, 8654, and 14024. DATES: Written comments should be received on or... . SUPPLEMENTARY INFORMATION: Title: VITA/TCE Program Forms. OMB Number: 1545-2222. Form Number: Forms 14310, 8653...

  13. 78 FR 2412 - Request for Public Comment: 30-Day Proposed Information Collection: Indian Health Service Forms...

    Science.gov (United States)

    2013-01-11

    ... Accounting of Disclosures,'' is used to document an individual's request for an accounting of disclosures of...-2) Request for Accounting of Disclosures (OMB Form 15,000 1 10/60 2,500 No. 0917-0030, IHS-913... receive a valid authorization for its use or disclosure of protected health information for other than for...

  14. A Simple Audit of Radiological Request Forms at the University of ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    with the managing team to clarify issues when necessary. CONCLUSION. In conclusion, we observed that radiological request forms are not always properly filled. Except for the name of the patient and the investigations requested, all other parameters were incompletely filled. This situation is a. The Nigerian Health Journal ...

  15. 77 FR 67792 - Proposed Information Collection; Comment Request; Northeast Region Permit Family of Forms

    Science.gov (United States)

    2012-11-14

    ... Collection; Comment Request; Northeast Region Permit Family of Forms AGENCY: National Oceanic and Atmospheric... offered in the Northeast region. Exemption programs may allow a vessel to fish in an area that is limited.... Vessels are also required to request gillnet and lobster tags through the Northeast region permit office...

  16. 76 FR 41763 - Proposed Information Collection; Comment Request; Alaska Region Logbook Family of Forms

    Science.gov (United States)

    2011-07-15

    ... Collection; Comment Request; Alaska Region Logbook Family of Forms AGENCY: National Oceanic and Atmospheric... (NMFS) Alaska Region manages the United States (U.S.) groundfish fisheries of the Exclusive Economic.... NMFS Alaska Region requests information from participating groundfish participants. This information...

  17. Fermilab Ed Office - High School Tour Request Form

    Science.gov (United States)

    will not work. Programs | Science Adventures | Calendar | Registration | About | Contact | FAQ capacity for physical science tours in April 2018. We will try to accommodate all requests but there is -St Charles CUSD 303-St Charles Kendall-Lisbon CCSD 90-Newark Kendall-Newark CCSD 66-Newark Kendall

  18. Potential for medical error: Incorrectly completed request forms for ...

    African Journals Online (AJOL)

    Thyroid-stimulating hormone (TSH) is a first-line thyroid function test and, if abnormal, reflex thyroxine (T4) or tri-iodothyronine (T3) testing is requested, depending on clinical and medication data provided. Interpretative comments are added to all TFT results. Objectives. In view of the paucity of articles describing such errors ...

  19. 78 FR 8225 - Proposed Collection; Comment Request for Form 1099-H

    Science.gov (United States)

    2013-02-05

    ... 1099-H AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 1099-H, Health Coverage Tax Credit (HCTC) Advance Payments. DATES: Written comments should be...: 1545-1813. Form Number: Form 1099-H. Abstract: Form 1099-H is used to report advance payments of health...

  20. 75 FR 2931 - Proposed Collection; Comment Request for Form 1099-H

    Science.gov (United States)

    2010-01-19

    ... 1099-H AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 1099-H, Health Coverage Tax Credit (HCTC) Advance Payments. DATES: Written comments should be.... OMB Number: 1545-1813. Form Number: Form 1099-H. Abstract: Form 1099-H is used to report advance...

  1. 77 FR 37098 - Proposed Collection; Comment Request for Form 8038-CP

    Science.gov (United States)

    2012-06-20

    ... 8038-CP AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 8038-CP, Return for Credit Payments to Issuers of Qualified Bonds. DATES: Written comments should... Issuers of Qualified Bonds. OMB Number: 1545-2142. Form Number: Form 8038-CP. Abstract: Form 8038-CP...

  2. 78 FR 6150 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2013-01-29

    ... home addresses of all employees hired within the last year (new-hires). Form BA-6a, Form BA-6 Address... RAILROAD RETIREMENT BOARD Agency Forms Submitted for OMB Review, Request for Comments Summary: In... collection techniques or other forms of information technology. Comments to the RRB or OIRA must contain the...

  3. 75 FR 5853 - Proposed Collection; Comment Request for Form 13803

    Science.gov (United States)

    2010-02-04

    ... 13803, Income Verification Express Service Application and Employee Delegation Form. DATES: Written... Application and Employee Delegation Form. OMB Number: 1545-2032. Form Number: Form 13803. Abstract: Form 13803, Income Verification Express Service Application and Employee Delegation Form, is used to submit the...

  4. audit of completion of radiology request form in a nigerian specialist

    African Journals Online (AJOL)

    X-ray unit of the over a period of six weeks to assess the completeness of filling of the ... outcome. Keywords: audit, radiology, request form, medical education .... times and for making business cases for expansion of services ... such risks.

  5. 78 FR 19649 - Proposed Information Collection; Comment Request; Southwest Region Permit Family of Forms

    Science.gov (United States)

    2013-04-02

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Southwest Region Permit Family of Forms AGENCY: National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice. SUMMARY: The Department of Commerce, as part of its continuing...

  6. 77 FR 47370 - Proposed Information Collection; Comment Request; Northeast Region Logbook Family of Forms

    Science.gov (United States)

    2012-08-08

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Northeast Region Logbook Family of Forms AGENCY: National Oceanic and Atmospheric Administration (NOAA). ACTION: Notice. SUMMARY: The Department of Commerce, as part of its...

  7. Microbiological method for radiation sterilization (III). Development of identification software of spore-forming bacteria by using BBL CRYSTAL GP identification kit

    International Nuclear Information System (INIS)

    Hironiwa, Takayuki; Yamamoto, Yoko; Koshikawa, Tomihiko

    2004-01-01

    The part III in this title series describes the development of software for identification of spore-forming bacteria using the commercially available BBL CRYSTAL GP Identification Kit (Becton, Dickinson and Co., Ltd.), which is essentially for identification of Gram positive bacteria and is not always suitable for the spore-former in the radiation sterilization of medical devices. Isolation and identification of a spore-forming bacterium have to be confirmed by phase-contrast microscopy. The bacteria cultured overnight are to be inoculated in the Kit and cultured for 18-24 hr at 35-37 deg C with the lid attached by substrates for identification. Here, 30 substrates and probability of positive reactions to the substrates have been tested for spore-formers to make the computer software for final identification. The system is possible to identify 13 spp. of Bacillus, 4 of Paenibacillus, 2 of Brevibaccilus and 1 of Virgibacillus, which are the usual bioburden. For possible misidentification, re-isolation of the bacterium, prolonged culture, concentrated inoculation and re-consideration for ranking of identification the software provides are necessary as well as other identification approaches. Thus, as described in this series, the radio-resistance of, and radiation dose for, the bioburden can be evaluated more easily than hitherto, with use of the kits in radiation sterilization. (N.I.)

  8. 78 FR 16918 - Proposed Collection; Comment Request for Form 976

    Science.gov (United States)

    2013-03-19

    ..., Public Law 104-13(44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 976..., or Real Estate Investment Trust. DATES: Written comments should be received on or before May 20, 2013... Company, or Real Estate Investment Trust. OMB Number: 1545-0045. Form Number: Form 976. Abstract: Form 976...

  9. 76 FR 71621 - Proposed Collection; Comment Request for Form 8892

    Science.gov (United States)

    2011-11-18

    ... 8892, Payment of Gift/GST Tax and/or Application for Extension to File Form 709. DATES: Written comments should be received on or before January 17, 2012 to be assured of consideration. ADDRESSES: Direct... Tax and/or Application for Extension to File Form 709. OMB Number: 1545-1913. Form Number: Form 8892...

  10. 76 FR 36622 - Proposed Collection; Comment Request for Form 5305A-SEP

    Science.gov (United States)

    2011-06-22

    ... 5305A-SEP AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 5305A-SEP, Salary Reduction Simplified Employee Pension-Individual Retirement Accounts... Agreement. OMB Number: 1545-1012. Form Number: 5305A-SEP. Abstract: Form 5305A-SEP is used by an employer to...

  11. 75 FR 5855 - Proposed Collection; Comment Request for Form 8038-TC

    Science.gov (United States)

    2010-02-04

    ... 8038-TC AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... comments concerning Form 8038-TC, Information Return for Tax Credit Bonds. DATES: Written comments should...: Form 8038-TC. Abstract: Form 8038-TC will be used by issuers of qualified tax- exempt credit bonds...

  12. 75 FR 30907 - Proposed Collection; Comment Request for Form 990-N

    Science.gov (United States)

    2010-06-02

    ... 990-N AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 990-N, Electronic Notice (e-Postcard) for Tax-Exempt Organizations not Required To file Form 990... Number: 1545-2085. Form Number: 990-N. Abstract: Section 1223 of the Pension Protection Act of 2006 (PPA...

  13. 76 FR 53168 - Proposed Collection; Comment Request for Form 1120-H

    Science.gov (United States)

    2011-08-25

    ... 1120-H AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 1120-H, U.S. Income Tax Return for Homeowners Associations. DATES: Written comments should be... Associations. OMB Number: 1545-0127. Form Number: 1120-H. Abstract: Homeowners associations file Form 1120-H to...

  14. 48 CFR 253.208-1 - DD Form 448, Military Interdepartmental Purchase Request.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 448, Military... DD Form 448, Military Interdepartmental Purchase Request. Follow the procedures at PGI 253.208-1 for use of DD Form 448. [71 FR 39005, July 11, 2006] ...

  15. 76 FR 37194 - Proposed Collection; Comment Request for Form 1099-R.

    Science.gov (United States)

    2011-06-24

    ... 1099-R. AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 1099-R, Distributions From Pensions, Annuities, Retirement or Profit-Sharing Plans, IRAs..., Insurance Contracts, etc. OMB Number: 1545-0119. Form Number: 1099-R. Abstract: Form 1099-R is used to...

  16. 78 FR 69938 - Proposed Collection; Comment Request for Form 8453-R

    Science.gov (United States)

    2013-11-21

    ... 8453-R AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 8453-R, Declaration and Signature for Electronic Filing of Forms 8947 and 8963. DATES: Written... copies of the form and instructions should be directed to R. Joseph Durbala, (202) 622-3634, at Internal...

  17. 78 FR 76892 - Proposed Collection; Comment Request for Form W-12

    Science.gov (United States)

    2013-12-19

    ... W-12 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form W-12 IRS Paid Preparer Tax Identification Number (PTIN). DATES: Written comments should be.... Form Number: Form W-12. Abstract: Paid tax return preparers are required to get a preparer tax...

  18. 75 FR 70971 - Proposed Collection; Comment Request for Form W-12

    Science.gov (United States)

    2010-11-19

    ... W-12 AGENCY: Internal Revenue Service, Treasury. ACTION: Notice and request for comments. SUMMARY..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form W...: 1545-2190. Form Number: Form W-12. Abstract: Paid tax return preparers will be required to get a...

  19. 76 FR 45906 - Proposed Collection; Comment Request for Form W-10

    Science.gov (United States)

    2011-08-01

    ... W-10 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form W-10, Dependent Care Provider's Identification and Certification. DATES: Written comments should... Certification. OMB Number: 1545-XXXX. Form Number: Form W-10. Abstract: The proposed collection of information...

  20. 76 FR 36618 - Proposed Collection; Comment Request for Form W-2G

    Science.gov (United States)

    2011-06-22

    ... W-2G AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form W-2G, Certain Gambling Winnings. DATES: Written comments should be received on or before August 22... INFORMATION: Title: Certain Gambling Winnings. OMB Number: 1545-0238. Form Number: Form W-2G. Abstract...

  1. 77 FR 38144 - Proposed Collection; Comment Request for Form 8594

    Science.gov (United States)

    2012-06-26

    ... reported includes the amount allocated to goodwill or going concern value. Form 8594 is used to report this..., Public Law 104-13(44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form...

  2. 75 FR 53018 - Proposed Collection; Comment Request for Form 720

    Science.gov (United States)

    2010-08-30

    .... Abstract: Form 720 is used to report (1) excise taxes due from retailers and manufacturers on the sale or... are no changes being made to the form at this time. Type of Review: Extension of a currently approved...

  3. 78 FR 70101 - Proposed Collection; Comment Request for Form 3800

    Science.gov (United States)

    2013-11-22

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 3800, General Business Credit. DATES: Written comments should be received on or before January 21, 2014... Business Credit. OMB Number: 1545-0895. Form Number: Form 3800. Abstract: Internal Revenue Code section 38...

  4. 76 FR 27748 - Proposed Collection; Comment Request for Form 8842

    Science.gov (United States)

    2011-05-12

    ..., Public Law 104-13(44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8842, Election To Use Different Annualization Periods for Corporate Estimated Tax. DATES: Written... Annualization Periods for Corporate Estimated Tax. OMB Number: 1545-1409. Form Number: 8842. Abstract: Form 8842...

  5. 76 FR 31015 - Proposed Collection; Comment Request for Form 8050

    Science.gov (United States)

    2011-05-27

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8050, Direct Deposit of Corporate Tax Refund. DATES: Written comments should be received on or before...: Direct Deposit of Corporate Tax Refund. OMB Number: 1545-1762. Form Number: 8050. Abstract: Form 8050 is...

  6. 75 FR 5868 - Proposed Collection; Comment Request for Form 966

    Science.gov (United States)

    2010-02-04

    ..., Public Law 104-13(44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 966, Corporate Dissolution or Liquidation. DATES: Written comments should be received on or before April 5, 2010...: Title: Corporate Dissolution or Liquidation. OMB Number: 1545-0041. Form Number: 966. Abstract: Form 966...

  7. 76 FR 77592 - Proposed Collection; Comment Request for Form 14242

    Science.gov (United States)

    2011-12-13

    ... . SUPPLEMENTARY INFORMATION: Title: Reporting Abusive Tax Promotions or Preparers. OMB Number: 1545-2219. Form Number: Form 14242. Abstract: The IC form is used to report an abusive tax avoidance scheme and tax... 14242, Reporting Abusive Tax Promotions or Preparers. DATES: Written comments should be received on or...

  8. 76 FR 57803 - Proposed Collection; Comment Request for Form 14242

    Science.gov (United States)

    2011-09-16

    ... . SUPPLEMENTARY INFORMATION: Title: Reporting Abusive Tax Promotions or Preparers. OMB Number: 1545-XXXX. Form Number: Form 14242. Abstract: The IC form is used to report an abusive tax avoidance scheme and tax... 14242, Reporting Abusive Tax Promotions or Preparers. DATES: Written comments should be received on or...

  9. 78 FR 78515 - Proposed Collection; Comment Request for Form 14242

    Science.gov (United States)

    2013-12-26

    ... INFORMATION: Title: Reporting Abusive Tax Promotions or Preparers. OMB Number: 1545-2219. Form Number: Form 14242. Abstract: The IC form is used to report an abusive tax avoidance scheme and tax return preparers... 14242, Reporting Abusive Tax Promotions or Preparers. DATES: Written comments should be received on or...

  10. 75 FR 40031 - Proposed Collection; Comment Request for Form 3800

    Science.gov (United States)

    2010-07-13

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 3800, General Business Credit. DATES: Written comments should be received on or before September 13... INFORMATION: Title: General Business Credit. OMB Number: 1545-0895. Form Number: Form 3800. Abstract: Internal...

  11. 75 FR 66427 - Proposed Collection; Comment Request for Form 13551

    Science.gov (United States)

    2010-10-28

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 13551, Application to Participate in the IRS Acceptance Agent Program. DATES: Written comments should be... Acceptance Agent Program. OMB Number: 1545-1896. Form Number: 13551. Abstract: Form 13551 is used to gather...

  12. 76 FR 36620 - Proposed Collection; Comment Request for Form 4797

    Science.gov (United States)

    2011-06-22

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 4797, Sales of Business Property. DATES: Written comments should be received on or before August [email protected] . SUPPLEMENTARY INFORMATION: Title: Sales of Business Property. OMB Number: 1545-0184. Form...

  13. 78 FR 16047 - Proposed Collection; Comment Request for Form 966

    Science.gov (United States)

    2013-03-13

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 966, Corporate Dissolution or Liquidation. DATES: Written comments should be received on or before May... . SUPPLEMENTARY INFORMATION: Title: Corporate Dissolution or Liquidation. OMB Number: 1545-0041. Form Number: 966...

  14. 76 FR 9077 - Proposed Collection; Comment Request for Form 2553

    Science.gov (United States)

    2011-02-16

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 2553, Election by a Small Business Corporation. DATES: Written comments should be received on or before... . SUPPLEMENTARY INFORMATION: Title: Election by a Small Business Corporation. OMB Number: 1545-0146. Form Number...

  15. 77 FR 71037 - Proposed Collection; Comment Request for Form 9452

    Science.gov (United States)

    2012-11-28

    ... 9452, Filing Assistance Program (Do you have to file a Federal Income Tax Return?). DATES: Written... Internet, at [email protected] . SUPPLEMENTARY INFORMATION: Title: Filing Assistance Program (Do you have to file a Federal Income Tax Return?). OMB Number: 1545-1316. Form Number: 9452. Abstract: Form...

  16. 78 FR 46414 - Proposed Collection; Comment Request for Form 8916

    Science.gov (United States)

    2013-07-31

    ... 8916, Reconciliation of Schedule M-3 Taxable Income with Tax Return Taxable Income for Mixed Groups... internet, at [email protected] . SUPPLEMENTARY INFORMATION: Title: Reconciliation of Schedule M-3 Taxable Income with Tax Return Taxable Income for Mixed Groups. OMB Number: 1545-2062. Form Number: Form...

  17. 75 FR 32989 - Proposed Collection; Comment Request for Form 706

    Science.gov (United States)

    2010-06-10

    ... 706, United States Estate (and Generation-Skipping Transfer) Tax Return. DATES: Written comments should be received on or before August 9, 2010 to be assured of consideration. ADDRESSES: Direct all... Transfer) Tax Return. OMB Number: 1545-0015. Form Number: 706. Abstract: Form 706 is used by executors to...

  18. 78 FR 54512 - Proposed Collection; Comment Request for Form 720

    Science.gov (United States)

    2013-09-04

    ... 720, Quarterly Federal Excise Tax Return. DATES: Written comments should be received on or before November 4, 2013 to be assured of consideration. ADDRESSES: Direct all written comments to Yvette Lawrence...: Quarterly Federal Excise Tax Return. OMB Number: 1545-0023. Form Number: 720. Abstract: Form 720 is used to...

  19. 78 FR 35660 - Proposed Collection; Comment Request for Form 1116

    Science.gov (United States)

    2013-06-13

    ... 1116, Foreign Tax Credit. DATES: Written comments should be received on or before August 12, 2013 to be assured of consideration. ADDRESSES: Direct all written comments to Yvette Lawrence, Internal Revenue...: Foreign Tax Credit. OMB Number: 1545-0121. Form Number: 1116. Abstract: Form 1116 is used by individuals...

  20. 78 FR 54514 - Proposed Collection; Comment Request for Form 8941

    Science.gov (United States)

    2013-09-04

    ... 8941, Credit for Small Employer Health Insurance Premiums. DATES: Written comments should be received... INFORMATION: Title: Credit for Small Employer Health Insurance Premiums. OMB Number: 1545-2198. Form Number... coverage expenses. Form 8941, Credit for Small Employer Health Insurance Premiums, has been developed to...

  1. 76 FR 55741 - Proposed Collection; Comment Request for Form 5305-SEP

    Science.gov (United States)

    2011-09-08

    ... 5305-SEP AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 5305-SEP, Simplified Employee Pension-Individual Retirement Accounts Contribution Agreement. DATES...: 5305-SEP. Abstract: Form 5305-SEP is used by an employer to make an agreement provide benefits to all...

  2. 78 FR 40824 - Proposed Collection; Comment Request for Form 8038-TC

    Science.gov (United States)

    2013-07-08

    ... 8038-TC AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 8038-TC, Information Return for Tax Credit Bonds. DATES: Written comments should be received on or...-TC. Abstract: Form 8038-TC will be used by issuers of qualified tax- exempt credit bonds, including...

  3. 78 FR 46692 - Proposed Collection; Comment Request for Form 990-N

    Science.gov (United States)

    2013-08-01

    ... 990-N AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 990-N, Electronic Notice (e-Postcard) for Tax-Exempt Organizations not Required To file Form 990... Number: 990-N. Abstract: Section 1223 of the Pension Protection Act of 2006 (PPA '06), enacted on August...

  4. 77 FR 64187 - Proposed Collection; Comment Request for Form 637 Questionnaires

    Science.gov (United States)

    2012-10-18

    ... 637 Questionnaires AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for... Questionnaires A, B, C, D, E, F, H, I, J, K, M, Q, R, S, T, UP, UV, V, W, X, and Y, Form 637 Questionnaires... information or copies of Form 637 Questionnaires should be directed to Allan Hopkins, (202)-622-6665, at...

  5. 77 FR 57197 - Proposed Collection; Comment Request for Form 1099-CAP

    Science.gov (United States)

    2012-09-17

    ... 1099-CAP AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 1099-CAP, Changes in Corporate Control and Capital Structure. DATES: Written comments should be... Structure. OMB Number: 1545-1814. Form Number: 1099-CAP. Abstract: Any corporation that undergoes...

  6. 78 FR 52824 - Proposed Information Collection (Bowel and Bladder Care Billing Form) Activity: Comment Request

    Science.gov (United States)

    2013-08-26

    ... and Bladder Care Billing Form) Activity: Comment Request AGENCY: Veterans Health Administration.... This notice solicits comments on the information needed to evaluate the Bowel and Bladder Care Billing Form used by caregivers of eligible Veterans to document time spent providing services related...

  7. 75 FR 55849 - Proposed Collection; Comment Request for Form 1097-BTC, Bond Tax Credit

    Science.gov (United States)

    2010-09-14

    ... 1097-BTC, Bond Tax Credit AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request... comments concerning Form 1097-BTC, Bond Tax Credit. DATES: Written comments should be received on or before... INFORMATION: Title: Form 1097-BTC, Bond Tax Credit. Abstract: This is an information return for reporting tax...

  8. 77 FR 64187 - Proposed Collection; Comment Request for Form 990-W

    Science.gov (United States)

    2012-10-18

    ... 990-W AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 990-W, Estimated Tax on Unrelated Business Taxable Income for Tax- Exempt Organizations. DATES... Business Taxable Income for Tax- Exempt Organizations. OMB Number: 1545-0976. Form Number: 990-W. Abstract...

  9. 77 FR 37699 - Notice of Proposed Information Collection: Comment Request OSHC Financial Reporting Form

    Science.gov (United States)

    2012-06-22

    ... Information Collection: Comment Request OSHC Financial Reporting Form AGENCY: Office of Sustainable Housing... Challenge Planning Grant Program, require the financial reporting by grantees. This tracking of grantee... also lists the following information: Title of Proposal: OSHC Financial Reporting Form. OMB Control...

  10. Analysis of radiological examination request forms in conjunction with justification of X-ray exposures

    International Nuclear Information System (INIS)

    Triantopoulou, Ch.; Tsalafoutas, I.; Maniatis, P.; Papavdis, D.; Raios, G.; Siafas, I.; Velonakis, S.; Koulentianos, E.

    2005-01-01

    Objectives: To evaluate the adequacy of patient data and clinical information transmitted to the radiological departments by the referring clinicians in view of the justification demands concerning the radiological examinations, as those are described in the Radiation Protection Regulations of the European Union Nations. Materials and methods: Request forms for 1708 patients referred to radiology department and 410 referred to the CT department were evaluated concerning the proper completion of the form fields. Furthermore, for CT examinations a more detailed evaluation was carried out, to assess the rationalistic use of CT within the diagnostic algorithm. Results: Not properly completed request forms to both departments were observed, however, the omissions were more prominent for the referrals to the radiology department, where the age and the probable clinical diagnosis was not given in 81.5 and 46% of the forms, respectively. Furthermore, the emergency indication was less cautiously used compared to the CT requests. For the CT department 33.3% of requests were justified and the final diagnosis was included in the referring doctor's probable clinical diagnosis. U/S was the examination of choice in 51% of the cases where an examination should have been performed before CT and in 70.6% of the cases where an alternative examination was proposed. Conclusions: The inadequate transmission of clinical information and the large number of not fully justified CT requests observed in this study are typical examples of the various problems that radiologists have to face in order to apply the justification directives

  11. 78 FR 10264 - Proposed Collection; Comment Request for Form 8870

    Science.gov (United States)

    2013-02-13

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8870, Information Return for Transfers Associated With Certain Personal Benefit Contracts. DATES: Written comments should be received on or before April 15, 2013 to be assured of consideration. ADDRESSES...

  12. 76 FR 12416 - Proposed Collection; Comment Request for Form 8939

    Science.gov (United States)

    2011-03-07

    ... Revenue Code requires this return to be filed by an executor the fair market value of all property (other.... Section 6018(e) also requires executors who must file Form 8939 to provide the same information to recipients of the property as the executor must provide to the IRS. Current Actions: There is no change in...

  13. 76 FR 30432 - Proposed Collection; Comment Request for Form 3115

    Science.gov (United States)

    2011-05-25

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 3115, Application for Change in Accounting Method. DATES: Written comments should be received on or....gov . SUPPLEMENTARY INFORMATION: Title: Application for Change in Accounting Method. OMB Number: 1545...

  14. 75 FR 33670 - Proposed Collection; Comment Request for Form 2032

    Science.gov (United States)

    2010-06-14

    ..., Public Law 104-13(44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 2032, Contract Coverage Under Title II of the Social Security Act. DATES: Written comments should [email protected] . SUPPLEMENTARY INFORMATION: Title: Contract Coverage Under Title II of the Social...

  15. 76 FR 34810 - Proposed Collection; Comment Request for Form 8810

    Science.gov (United States)

    2011-06-14

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8810, Corporate Passive Activity Loss and Credit Limitations. DATES: Written comments should be... [email protected] . [[Page 34811

  16. 76 FR 77051 - Proposed Collection; Comment Request for Form 5452

    Science.gov (United States)

    2011-12-09

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 5452, Corporate Report of Nondividend Distributions. DATES: Written comments should be received on or....gov . SUPPLEMENTARY INFORMATION: Title: Corporate Report of Nondividend Distributions. OMB Number...

  17. 78 FR 46690 - Proposed Collection; Comment Request for Form 8855

    Science.gov (United States)

    2013-08-01

    ... of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8855, Election To Treat a Qualified Revocable Trust as Party of an Estate. DATES: [email protected] . SUPPLEMENTARY INFORMATION: Title: Election To Treat a Qualified Revocable Trust as Party of...

  18. 77 FR 71481 - Proposed Collection; Comment Request for Form 8911

    Science.gov (United States)

    2012-11-30

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... collection of information unless the collection of information displays a valid OMB control number. Books or... material in the administration of any internal revenue law. Generally, tax returns and tax return...

  19. 78 FR 48773 - Proposed Collection; Comment Request for Form 8866

    Science.gov (United States)

    2013-08-09

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form.... Books or records relating to a collection of information must be retained as long as their contents may become material in the administration of any internal revenue law. Generally, tax returns and tax return...

  20. 77 FR 31913 - Proposed Collection; Comment Request for Form 7004

    Science.gov (United States)

    2012-05-30

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... OMB control number. Books or records relating to a collection of information must be retained as long as their contents may become material in the administration of any internal revenue law. Generally...

  1. 78 FR 42819 - Proposed Collection; Comment Request for Form 709

    Science.gov (United States)

    2013-07-17

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... information displays a valid OMB control number. Books or records relating to a collection of information must... revenue law. Generally, tax returns and tax return information are confidential, as required by 26 U.S.C...

  2. 78 FR 28020 - Proposed Collection: Comment Request for Form 2032

    Science.gov (United States)

    2013-05-13

    ..., Public Law 104-13(44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... collection of information displays a valid OMB control number. Books or records relating to a collection of... internal revenue law. Generally, tax returns and tax return information are confidential, as required by 26...

  3. 76 FR 77326 - Proposed Collection; Comment Request for Form 56

    Science.gov (United States)

    2011-12-12

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 56... information unless the collection of information displays a valid OMB control number. Books or records... the administration of any internal revenue law. Generally, tax returns and tax return information are...

  4. 76 FR 74117 - Proposed Collection; Comment Request for Form 4810

    Science.gov (United States)

    2011-11-30

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... collection of information displays a valid OMB control number. Books or records relating to a collection of... internal revenue law. Generally, tax returns and tax return information are confidential, as required by 26...

  5. 76 FR 65320 - Proposed Collection; Comment Request for Form 4029

    Science.gov (United States)

    2011-10-20

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... information displays a valid OMB control number. Books or records relating to a collection of information must... revenue law. Generally, tax returns and tax return information are confidential, as required by 26 U.S.C...

  6. 78 FR 60378 - Proposed Collection; Comment Request for Form 1023

    Science.gov (United States)

    2013-10-01

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... displays a valid OMB control number. Books or records relating to a collection of information must be retained as long as their contents may become material in the administration of any internal revenue law...

  7. 78 FR 13157 - Proposed Collection; Comment Request for Form 13803

    Science.gov (United States)

    2013-02-26

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... information displays a valid OMB control number. Books or records relating to a collection of information must... revenue law. Generally, tax returns and tax return information are confidential, as required by 26 U.S.C...

  8. 78 FR 57219 - Proposed Collection; Comment Request for Form 4562

    Science.gov (United States)

    2013-09-17

    ... 4562, Depreciation and Amortization (Including Information on Listed Property). DATES: Written comments... 20224, or through the internet, at [email protected] . SUPPLEMENTARY INFORMATION: Title: Depreciation... 4562. Abstract: Form 4562 is used to claim a deduction for depreciation and amortization; to make the...

  9. 78 FR 69529 - Proposed Collection; Comment Request for Form 8945

    Science.gov (United States)

    2013-11-19

    .... This form is being submitted for renewal purposes only. Type of Review: Extension of a currently... burden, invites the general public and other Federal agencies to take this opportunity to comment on proposed and/or continuing information collections, as required by the Paperwork Reduction Act of 1995...

  10. 75 FR 38183 - Proposed Collection; Comment Request for Form 8916

    Science.gov (United States)

    2010-07-01

    ... 8916, Reconciliation of Schedule M-3 Taxable Income with Tax Return Taxable Income for Mixed Groups... through the Internet, at [email protected] . SUPPLEMENTARY INFORMATION: Title: Reconciliation of Schedule M-3 Taxable Income with Tax Return Taxable Income for Mixed Groups. OMB Number: 1545-2062. Form...

  11. 77 FR 57194 - Proposed Collection; Comment Request for Form 8611

    Science.gov (United States)

    2012-09-17

    ... 8611, Recapture of Low-Income Housing Credit. DATES: Written comments should be received on or before..., DC 20224, or at (202) 622-6665, or through the Internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: Recapture of Low-Income Housing Credit. OMB Number: 1545-1035. Form Number: 8611. Abstract...

  12. 78 FR 52235 - Proposed Collection; Comment Request for Form 8825

    Science.gov (United States)

    2013-08-22

    ... Form 8825, Rental Real Estate Income and Expenses of a Partnership or an S Corporation. DATES: Written..., Room 6129, 1111 Constitution Avenue NW., Washington DC 20224, or through the internet, at [email protected] . SUPPLEMENTARY INFORMATION: Title: Rental Real Estate Income and Expenses of a...

  13. 76 FR 62499 - Proposed Collection; Comment Request for Form 8693

    Science.gov (United States)

    2011-10-07

    ... 8693, Low-Income Housing Credit Disposition Bond. DATES: Written comments should be received on or...., Washington, DC 20224, or at (202) 622-3179, or through the Internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: Low-Income Housing Credit Disposition Bond. OMB Number: 1545-1029. Form Number...

  14. 77 FR 68887 - Proposed Collection; Comment Request for Form 2063

    Science.gov (United States)

    2012-11-16

    ... 2063, U.S. Departing Alien Income Tax Statement. DATES: Written comments should be received on or... NW., Washington, DC 20224, or at (202) 622-3869, or through the Internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: U.S. Departing Alien Income Tax Statement. OMB Number: 1545-0138. Form Number...

  15. 76 FR 10669 - Proposed Collection; Comment Request for Form 8896

    Science.gov (United States)

    2011-02-25

    ... section 45H allows small business refiners to claim a credit for the production of low sulfur diesel fuel. The American Jobs Creation Act of 2004 section 399 brought it into existence. Form 8896 will allow...: Business or other for-profit organizations. Estimated Number of Respondents: 66. Estimated Total Annual...

  16. 78 FR 63566 - Proposed Collection; Comment Request for Form 8838

    Science.gov (United States)

    2013-10-24

    ... concerning Form 8838, Consent To Extend the Time To Assess Tax Under Section 367-Gain Recognition Agreement.... ADDRESSES: Direct all written comments to Yvette Lawrence, Internal Revenue Service, Room 6129, 1111... . SUPPLEMENTARY INFORMATION: Title: Consent To Extend the Time To Assess Tax Under Section 367- Gain Recognition...

  17. 78 FR 58606 - Proposed Collection; Comment Request for Form 3911

    Science.gov (United States)

    2013-09-24

    ... or before November 25, 2013 to be assured of consideration. ADDRESSES: Direct all written comments to.... Abstract: Form 3911 is used by taxpayers to notify the IRS that a tax refund previously claimed has not... taxpayer claims non-receipt, loss, theft, or destruction of a tax refund and IRS research shows that the...

  18. 75 FR 5855 - Proposed Collection; Comment Request for Form 6197

    Science.gov (United States)

    2010-02-04

    ... 6197, Gas Guzzler Tax. DATES: Written comments should be received on or before April 5, 2010 to be assured of consideration. ADDRESSES: Direct all written comments to R. Joseph Durbala, Internal Revenue... Guzzler Tax. OMB Number: 1545-0242. Form Number: 6197. Abstract: Internal Revenue Code section 4064...

  19. 77 FR 35479 - Proposed Collection; Comment Request for Form 8881

    Science.gov (United States)

    2012-06-13

    ...The Department of the Treasury, as part of its continuing effort to reduce paperwork and respondent burden, invites the general public and other Federal agencies to take this opportunity to comment on proposed and/or continuing information collections, as required by the Paperwork Reduction Act of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8881, Credit for Small Employer Pension Plan Startup Costs.

  20. 41 CFR 101-26.4904-416 - DD Form 416: Purchase Request for Coal, Coke, or Briquettes.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true DD Form 416: Purchase Request for Coal, Coke, or Briquettes. 101-26.4904-416 Section 101-26.4904-416 Public Contracts and... DD Form 416: Purchase Request for Coal, Coke, or Briquettes. Note: The form illustrated in § 101-26...

  1. 76 FR 49538 - Proposed Collection; Comment Request for Forms 8027 and 8027-T

    Science.gov (United States)

    2011-08-10

    .... Abstract: To help IRS in its examinations of returns filed by tipped employees, large food or beverage establishments are required to report annually information concerning food or beverage operations receipts, tips... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Forms...

  2. 20 CFR 726.307 - Form of notice of contest and request for hearing.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Form of notice of contest and request for hearing. 726.307 Section 726.307 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT OF.... In particular, the person must indicate his agreement or disagreement with: (i) The Director's...

  3. 78 FR 21912 - Proposed Information Collection; Comment Request; Processed Products Family of Forms

    Science.gov (United States)

    2013-04-12

    ... Collection; Comment Request; Processed Products Family of Forms AGENCY: National Oceanic and Atmospheric... NOAA in the economic and social analyses developed when proposing and evaluating fishery management... collection). Affected Public: Business or other for-profit organizations. Estimated Number of Respondents...

  4. 75 FR 61763 - Submission of OMB Review; Comment Request; Drug Accountability Record (Form NIH 2564) (NCI)

    Science.gov (United States)

    2010-10-06

    ...; Comment Request; Drug Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the..., 2011, unless it displays a valid OMB control number. Proposed Collection: Title: Drug Accountability... accountability. In order to fulfill these requirements, a standard Investigational Drug Accountability Report...

  5. 75 FR 46945 - Proposed Collection; Comment Request; the Drug Accountability Record (Form NIH 2564) (NCI)

    Science.gov (United States)

    2010-08-04

    ... Request; the Drug Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the requirement... Management and Budget (OMB) for review and approval. Proposed Collection Title: The Drug Accountability... agent accountability. In order to fulfill these requirements, a standard Investigational Drug...

  6. 78 FR 25416 - Information Collection Request: Web-Based Supply Chain Management Commodity Offer Forms

    Science.gov (United States)

    2013-05-01

    ... Request: Web-Based Supply Chain Management Commodity Offer Forms AGENCY: Farm Service Agency and Commodity..., and yearly bases. Special invitations, however, are issued throughout the month. Web-Based Supply Chain Management (WBSCM) allows respondents to submit information electronically. DATES: Comments on...

  7. Laboratory Request Forms- How Well do Doctors Fill Them? A Look ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    Effect of pre-analytic errors on quality of laboratory Medicine at a neuropsychiatric institute inN orth India. IndJ ClinBiochem. 2011; 26(1): 46-49. 8. Oladeinde BH, Omeregie R, Osakue EO,. Onifade AO. Evaluation of laboratory request forms for incomplete data at a rural tertiary hospital in Nigeria. NZJ. Med Lab. 2012; 66; 2: ...

  8. 78 FR 77095 - Agency Information Collection Activities: Proposed Collection; Comment Request-Form FNS-648, WIC...

    Science.gov (United States)

    2013-12-20

    ... DEPARTMENT OF AGRICULTURE Food and Nutrition Service Agency Information Collection Activities: Proposed Collection; Comment Request--Form FNS-648, WIC Local Agency Directory Report AGENCY: Food and... continuity of program services to migrant and other transient participants. It is also used as a mailing list...

  9. 75 FR 80861 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2010-12-23

    ... collection techniques or other forms of information technology. Comments to RRB or OIRA must contain the OMB..., information needed to ensure secure system access from employers who voluntarily opt to use the RRB's Internet... (RRB) is submitting five (5) Information Collection Requests (ICR) to the Office of Information and...

  10. 15 CFR Appendix I to Part 700 - Form BIS-999-Request for Special Priorities Assistance

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Form BIS-999-Request for Special Priorities Assistance I Appendix I to Part 700 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL...

  11. 78 FR 27260 - Comment Request: Antarctic Conservation Act Application Permit Form

    Science.gov (United States)

    2013-05-09

    ... several years. The form requests general information, such as name, affiliation, location, etc., and more specific information as to the type of object to be taken (plant, native mammal, or native bird. Use of the Information The purpose of the regulations (45 CFR 670) is to conserve and protect the native mammals, birds...

  12. 75 FR 35843 - Proposed Extension of Information Collection Request Submitted for Public Comment; Form 5500...

    Science.gov (United States)

    2010-06-23

    ... welfare plans (collectively referred to as employee benefit plans) to file returns or reports annually... DEPARTMENT OF LABOR Employee Benefits Security Administration Proposed Extension of Information Collection Request Submitted for Public Comment; Form 5500, Annual Return/Report of Employee Benefit Plan...

  13. 77 FR 38145 - Proposed Collection; Comment Request for Form 1099-U.

    Science.gov (United States)

    2012-06-26

    .... accounts. Form 1099-U is used to improve monitoring and tax compliance of U.S. Citizens, and Residents with.... Generally, tax returns and tax return information are confidential, as required by 26 U.S.C. 6103. Request... information technology; and (e) estimates of capital or start-up costs and costs of operation, maintenance...

  14. 76 FR 21946 - Proposed Collection; Comment Request for Form 990-BL; Schedule A (Form 990-BL), Form 6069

    Science.gov (United States)

    2011-04-19

    ... Initial Excise Tax Return for Black Lung Benefit Trusts and Certain Related Persons, and Form 6069, Return of Excise Tax on Excess Contributions to Black Lung Benefit Trust Under Section 4953 and Computation...: Form 990-BL, Schedule A (Form 990-BL), Information and Initial Excise Tax Return for Black Lung Benefit...

  15. 76 FR 36620 - Proposed Collection; Comment Request for Form 8453-F and Form 8879-F

    Science.gov (United States)

    2011-06-22

    ... 1995, Public Law 104-13(44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8453-F, U.S. Estate of Trust Income Tax Declaration and Signature for Electronic and Magnetic Made... Joel.Goldberger.irs.gov . SUPPLEMENTARY INFORMATION: Title: U.S. Estate of Trust Income Tax Declaration...

  16. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  17. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

    Science.gov (United States)

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E; Schief, William R; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D

    2010-01-19

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  18. 77 FR 38582 - Proposed Information Collection; Comment Request; Domestic Client Life-Cycle Multi-Purpose Forms

    Science.gov (United States)

    2012-06-28

    ... Request; Domestic Client Life-Cycle Multi-Purpose Forms AGENCY: International Trade Administration. ACTION..., 0625-0237, and 0625-0238. These collections include all client intake, events/activities and export... Client Life-cycle Multi-Purpose Forms, previously titled Export Information Services Order Forms, are...

  19. 75 FR 7522 - Peer Review, Conflict of Interest and Disclosure Form; Request for the Office of Management and...

    Science.gov (United States)

    2010-02-19

    ... Review, Conflict of Interest and Disclosure Form; Request for the Office of Management and Budget's (OMB... proposal to extend the Office of Management and Budget's (OMB) approval of the Conflict of Interest (COI) and Disclosure Form which is used to determine whether or not a conflict of interest exists for a...

  20. Microsoft Dynamics GP 2013 implementation

    CERN Document Server

    Yudin, Victoria

    2013-01-01

    A step-by-step guide for planning and carrying out your Microsoft Dynamics GP 2013 implementation. Detailed descriptions and illustrations of setup screens and practical examples and advice are included for the Dynamics GP system and core modules.If you are a new or existing Microsoft Dynamics GP consultant or an end user who wants to implement, install, and set up core modules of Dynamics GP 2013, then this book is for you. A basic understanding of business management systems and either Dynamics GP or a similar application is recommended.

  1. 76 FR 41313 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2011-07-13

    ... 2(f)(6) of the RRA, earnings deductions are required each month an annuitant works in certain... respondent. Completion is required to obtain or retain benefits. Previous Requests for Comments: The RRB has...

  2. Determinants of a GP visit and cervical cancer screening examination in Great Britain.

    Directory of Open Access Journals (Sweden)

    Alexander Michael Labeit

    Full Text Available In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP.A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey.The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination.Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test.

  3. 75 FR 44849 - Proposed Collection; Comment Request for Forms 945, 945-A, and 945-V

    Science.gov (United States)

    2010-07-29

    ... Liability; and Form 945-V, Form 945 Payment Voucher. DATES: Written comments should be received on or before... Liability (Form 945-A), and Form 945 Payment Voucher (Form 945-V). OMB Number: 1545-1430. Form Numbers: 945... winnings. Form 945-A is used to report nonpayroll tax liabilities. Form 945-V is a payment voucher that is...

  4. A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120

    International Nuclear Information System (INIS)

    Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P.

    2007-01-01

    The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1 JR-FL . Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140 UNC ), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1 JR-FL . All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1 JR-FL were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes

  5. Low-energy analysis of the nucleon electromagnetic form factors[12.39.Fe; 13.40.Gp; 14.20.Dh; Nucleon electromagnetic form factors; Chiral perturbation theory

    Energy Technology Data Exchange (ETDEWEB)

    Kubis, Bastian. E-mail: b.kubis@fz-juelich.de; Meissner, Ulf-G. E-mail: Ulf-G.Meissner@fz-juelich.de

    2001-01-01

    We analyze the electromagnetic form factors of the nucleon to fourth order in relativistic baryon chiral perturbation theory. We employ the recently proposed infrared regularization scheme and show that the convergence of the chiral expansion is improved as compared to the heavy-fermion approach. We also discuss the inclusion of vector mesons and obtain an accurate description of all four-nucleon form factors for momentum transfer squared up to Q{sup 2}{approx_equal}0.4 GeV{sup 2}.

  6. 75 FR 44030 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2010-07-27

    ... Affairs (OIRA), Office of Management and Budget (OMB) to request an extension of an existing collection of...-49R, Letter to Railroad Employers for Payroll Information, and UI-48, Claimant's Statement Regarding... [email protected] and to the OMB Desk Officer for the RRB, at the Office of Management and Budget...

  7. 5 CFR 2502.6 - How to request records-form and content.

    Science.gov (United States)

    2010-01-01

    ... PRESIDENT AVAILABILITY OF RECORDS Production or Disclosure of Records Under the Freedom of Information Act... or official who receives an oral request made under the FOIA shall inform the person making the... reasonably descriptive, or requires the production of voluminous records, or places an extraordinary burden...

  8. 24 CFR 2002.21 - Authority to deny requests for records and form of denial.

    Science.gov (United States)

    2010-04-01

    ... of a record or information compiled by a criminal law enforcement authority in the course of a...) Be in writing; (2) State simply the reasons for the denial; (3) State that review of the denial by the Inspector General of HUD may be requested; (4) Set forth the steps for obtaining review consistent...

  9. 77 FR 58401 - Proposed Collection: Comment Request: Drug Accountability Report Form and Investigator...

    Science.gov (United States)

    2012-09-20

    ... for record keeping is estimated to require 14,223 hours (see Table 1). There are no capital costs, operating costs, or maintenance costs. Table 1--Estimates of Annual Burden Average time Type of respondents...) (OMB No. 0925-0613). Type of Information Collection Request: Revision. Need and Use of Information...

  10. Using an adapted form of the picture exchange communication system to increase independent requesting in deafblind adults with learning disabilities.

    Science.gov (United States)

    Bracken, Maeve; Rohrer, Nicole

    2014-02-01

    The current study assessed the effectiveness of an adapted form of the Picture Exchange Communication System (PECS) in increasing independent requesting in deafblind adults with learning disabilities. PECS cards were created to accommodate individual needs, including adaptations such as enlarging photographs and using swelled images which consisted of images created on raised line drawing paper. Training included up to Phase III of PECS and procedures ensuring generalizations across individuals and contexts were included. The effects of the intervention were evaluated using a multiple baseline design across participants. Results demonstrated an increase in independent requesting with each of the participants reaching mastery criterion. These results suggest that PECS, in combination with some minor adaptations, may be an effective communicative alternative for individuals who are deafblind and have learning impairments. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. 76 FR 30430 - Proposed Collection; Comment Request for Form 5713 and Schedules A, B, and C (Form 5713)

    Science.gov (United States)

    2011-05-25

    ... of income of a domestic international sales corporation, or deferral of income of a foreign sales... of automated collection techniques or other forms of information technology; and (e) estimates of...

  12. 75 FR 51531 - Proposed Collection; Comment Request for Forms 941, 941-PR, 941-SS, 941-X, 941-X(PR), Schedule B...

    Science.gov (United States)

    2010-08-20

    ... 941, 941-PR, 941- SS, 941-X, 941-X(PR), Schedule B (Form 941), Schedule R (Form 941) and Schedule B (Form 941-PR) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... comments concerning Forms 941 (Employer's Quarterly Federal Tax Return), 941-PR (Planilla Para La...

  13. 78 FR 47056 - Proposed Collection; Comment Request for Forms 941, 941-PR, 941-SS, 941-X, 941-X(PR), Schedule B...

    Science.gov (United States)

    2013-08-02

    ... 941, 941-PR, 941- SS, 941-X, 941-X(PR), Schedule B (Form 941), Schedule R (Form 941)and Schedule B (Form 941-PR) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Forms 941 (Employer's Quarterly Federal Tax Return), 941-PR, 941-SS (Employer's Quarterly Federal Tax...

  14. Psychosocial factors in GP work: the effects of taking a GP position or leaving GP work.

    Science.gov (United States)

    Heponiemi, Tarja; Kouvonen, Anne; Aalto, Anna-Mari; Elovainio, Marko

    2013-06-01

    We examined the effects of leaving public sector general practitioner (GP) work and of taking a GP position on changes in work-related psychosocial factors, such as time pressure, patient-related stress, distress and work interference with family. In addition, we examined whether changes in time pressure and patient-related stress mediated the association of employment change with changes of distress and work interference with family. Participants were 1705 Finnish physicians (60% women) who responded to surveys in 2006 and 2010. Analyses of covariance were conducted to examine the effect of employment change to outcome changes adjusted for gender, age and response format. Mediational effects were tested following the procedures outlined by Baron and Kenny. Employment change was significantly associated with all the outcomes. Leaving public sector GP work was associated with substantially decreased time pressure, patient-related stress, distress and work interference with family. In contrast, taking a position as a public sector GP was associated with an increase in these factors. Mediation tests suggested that the associations of employment change with distress change and work interference with family change were partially explained by the changes in time pressure and patient-related stress. Our results showed that leaving public sector GP work is associated with favourable outcomes, whereas taking a GP position in the public sector is associated with adverse effects. Primary health-care organizations should pay more attention to the working conditions of their GPs, in particular, to time pressure and patient-related stress.

  15. 75 FR 72847 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2010-11-26

    ... Form RRB W-4P annually. The completion time for Form RRB W-4P varies depending on individual circumstances. The estimated average(s) for Form RRB W-4P is 39 minutes for recordkeeping, 24 minutes for...: 3220-0149. Form(s) submitted: RRB-W-4P, Withholding Certificate for Railroad Retirement Monthly Annuity...

  16. 75 FR 69716 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2010-11-15

    ..., consisting of proposed RRB Form G-252, Self-Employment/Corporate Officer Work and Earnings Monitoring. Our... retain benefits. One response is required of each respondent. Review and approval by OIRA ensures that we...: Self-Employment/Corporate Officer Work and Earnings Monitoring. OMB Control Number: 3220-XXXX. Form(s...

  17. 77 FR 36608 - Proposed Collection; Comment Request for Form 56-A

    Science.gov (United States)

    2012-06-19

    ... 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 56-A, Notice Concerning Fiduciary Relationship--Illinois Type Land Trust. DATES: Written comments... Relationship-- Illinois Type Land Trust. OMB Number: 1545-1683. Form Number: 56-A. Abstract: Form 56-A will be...

  18. 76 FR 53168 - Proposed Collection; Comment Request for Form 990-EZ

    Science.gov (United States)

    2011-08-25

    ... Form 990-EZ, Short Form Return of Organization Exempt from Income Tax. DATES: Written comments should be received on or before October 24, 2011 to be assured of consideration. ADDRESSES: Direct all... From Income Tax. OMB Number: 1545-1150. Form Number: 990-EZ. Abstract: An annual return is required by...

  19. 78 FR 58607 - Proposed Collection; Comment Request for Form 1041-ES

    Science.gov (United States)

    2013-09-24

    ... Form 1041-ES, Estimated Income Tax for Estates and Trusts. DATES: Written comments should be received on or before November 25, 2013 to be assured of consideration. ADDRESSES: Direct all written comments... INFORMATION: Title: Estimated Income Tax for Estates and Trusts. OMB Number: 1545-0971. Form Number: Form 1041...

  20. Auditing The Completeness and Legibility of Computerized Radiological Request Forms.

    Science.gov (United States)

    Al Muallem, Yahya; Al Dogether, Majed; Househ, Mowafa; Saddik, Basema

    2017-11-04

    Certain Saudi healthcare organizations transfer outpatients to medical imaging departments for radiological examinations in a manual process that relies on the use of paper-based forms. With the increased implementation of electronic medical records in Saudi Hospitals, little is known about the completeness and legibility of information captured in  electronic-based medical imaging forms. The purpose of this study is to audit the completeness and legibility of medical imaging paper-based forms in comparison with electronic-based medical imaging forms. As a secondary objective, we also examined the number of errors found on the forms.An observational retrospective cross-sectional study was utilized to audit the completeness and legibility of both paper and electronic forms collected between March 1 and May 15, 2015. The study measured the association among categorical variables using Chi-Square analysis. The results of this investigation show a significant association between form completion and type of record (i.e., paper vs. electronic) where electronic-based systems were found to be more complete than paper-based records. Electrnoic based records were also found to improve form legibility, promote user adherence to complete the forms and minimize entry errors. In conclusion, electronic-based medical imaging forms are more complete and legible than paper based forms. Future studies should evaluate other hospitals and compare both legibility and completeness of electronic-based medical imaging forms and conduct usability evaluation studies with users to explore the impacts of system design on both completeness and legibility of electronic forms, in general, but more specifically, electronic-based medical imaging forms.

  1. 75 FR 40028 - Proposed Collection; Comment Request for Form 8283-V

    Science.gov (United States)

    2010-07-13

    ... Form 8283-V, Payment Voucher for Filing Fee Under Section 170(f)(13). DATES: Written comments should [email protected] . SUPPLEMENTARY INFORMATION: Title: Payment Voucher for Filing Fee Under... deduction is not allowed. Current Actions: There are no changes being made to Form 8283-V. Type of Review...

  2. 76 FR 52026 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2011-08-19

    ...: Application for Reimbursement for Hospital Insurance Services in Canada OMB Control Number: 3220-0086 Form(s... to enhance the quality, utility, and clarity of the information that is the subject of collection... OMB control number of the ICR. For proper consideration of your comments, it is best if the RRB and...

  3. 77 FR 55229 - National Farmworker Jobs Program (NFJP) Information Collection Forms; Comment Request for Regular...

    Science.gov (United States)

    2012-09-07

    ... the grantees regarding the content of the annual plan narrative and submission requirements. II... through the use of appropriate automated, electronic, mechanical, or other technological collection.... Affected Public: State or local government agencies; not-for-profit organizations. Form(s): Grant Plan...

  4. 78 FR 58608 - Proposed Collection; Comment Request for the EFTPS Primary Contact Information Change Form

    Science.gov (United States)

    2013-09-24

    ... form is being submitted for renewal purposes only. Type of Review: Extension of a currently approved... EFTPS Primary Contact Information Change Form AGENCY: Internal Revenue Service (IRS), Treasury. ACTION... effort to reduce paperwork and respondent burden, invites the general public and other Federal agencies...

  5. 78 FR 3498 - Proposed Collection; Comment Request for Form 14417-A

    Science.gov (United States)

    2013-01-16

    ... Form 14417-A, Statistics of Income--User Fee. DATES: Written comments should be received on or before... Avenue NW., Washington, DC 20224, or through the internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: Statistics of Income--User Fee. OMB Number: 1545-2235. Form Number: 14417-A. Abstract...

  6. 76 FR 71389 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2011-11-17

    ... Interchange (EDI) version of the Form Letter ID-4K notice, or an Internet equivalent ID-4K, which is... electronically via EDI or ERS. Completion is voluntary. Once the RRB determines to pay a claim post-payment Form...-4E paper notice and the EDI and Internet equivalent versions are transmitted on a daily basis...

  7. 75 FR 5863 - Proposed Collection; Comment Request for Forms 8453-C and 8453-I

    Science.gov (United States)

    2010-02-04

    ... Form 8453-C, U.S. Corporation Income Tax Declaration for an IRS e-file Return and Form 8453-I, Foreign Corporation Income Tax Declaration for an IRS e-file Return. DATES: Written comments should be received on or before April 5, 2010 to be assured of consideration. ADDRESSES: Direct all written comments to R. Joseph...

  8. 78 FR 63565 - Proposed Collection; Comment Request for Forms 2210 and 2210-F

    Science.gov (United States)

    2013-10-24

    ... Form 2210, Underpayment of Estimated Tax by Individuals, Estate, and Trusts, and Form 2210-F, Underpayment of Estimated Tax by Farmers and Fishermen. DATES: Written comments should be received on or before December 23, 2013 to be assured of consideration. ADDRESSES: Direct all written comments to Yvette B...

  9. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

    Science.gov (United States)

    Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

    2016-08-08

    The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

  10. 78 FR 57218 - Proposed Collection; Comment Request for Form 8283-V

    Science.gov (United States)

    2013-09-17

    ... Form 8283-V, Payment Voucher for Filing Fee Under Section 170(f)(13). DATES: Written comments should be... . SUPPLEMENTARY INFORMATION: Title: Payment Voucher for Filing Fee Under Section 170(f)(13). OMB Number: 1545-2069...

  11. 78 FR 9432 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2013-02-08

    ... techniques or other forms of information technology. Comments to the RRB or OIRA must contain the OMB control... permanent disability for work in the applicants ``regular occupation'' or for work in any regular employment...

  12. 77 FR 31897 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2012-05-30

    ... techniques or other forms of information technology. Comments to the RRB or OIRA must contain the OMB control... quarterly contributions to the RRB. Employers can use either the manual version of the [[Page 31898

  13. 78 FR 19573 - Proposed Collection; Comment Request for Form 8879-B

    Science.gov (United States)

    2013-04-01

    ...: 1545-2043. Form Number: 8879-B. Abstract: A general partner or a limited liability company member... an electing large partnership's electronic income tax return, and, if applicable, consent to an...

  14. 76 FR 33025 - Proposed Collection; Comment Request for Form 720X

    Science.gov (United States)

    2011-06-07

    ... of Form 720X is the result of a project to provide a uniform standard for trust fund accounting.... Books or records relating to a collection of information must be retained as long as their contents may... information is necessary for the proper performance of the functions of the agency, including whether the...

  15. 75 FR 15754 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2010-03-30

    ...'s marital history, work history, military service, benefits from other governmental agencies and.... The application and related forms obtain information about the applicant's family work history... beneficiaries, claimants, employers and members of the public want and expect, as well as their satisfaction...

  16. 78 FR 53174 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2013-08-28

    ... Affairs (OIRA), Office of Management and Budget (OMB). Our ICR describes the information we seek to..., Railroad Payroll Record Check; and Form UI-48, Statement Regarding Benefits Claimed for Days Worked...: [email protected] . Charles Mierzwa, Chief of Information Resources Management. [FR Doc. 2013...

  17. 76 FR 52638 - Proposed Information Collection; Comment Request; Shipboard Observation Form for Floating Marine...

    Science.gov (United States)

    2011-08-23

    ... Paperwork Clearance Officer, Department of Commerce, Room 6616, 14th and Constitution Avenue, NW... of this form is to be able to calculate the density of marine debris within an area of a known size... institutions. Estimated Number of Respondents: 60. Estimated Time per Response: 45 minutes. Estimated Total...

  18. 78 FR 26766 - Commission Information Collection Activities (FERC Form 580); Comment Request; Revision

    Science.gov (United States)

    2013-05-08

    ... purchase contracts/agreement. The language will be similar to what was used in Form No. 580 interrogatories... generation and thermal energy of Question 6 for fuel oil no. associated with the production of 2 is necessary. Report all electricity. Information for only fuels consumed for electric coal, natural gas, and oil...

  19. 77 FR 64378 - Proposed Collection; Comment Request for Form 3520-A

    Science.gov (United States)

    2012-10-19

    ... 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 3520-A, Annual Information Return of Foreign Trust With a U.S. Owner. DATES: Written [email protected] . SUPPLEMENTARY INFORMATION: Title: Annual Information Return of Foreign Trust With A U.S...

  20. 76 FR 44658 - Proposed Collection; Comment Request for Form 1041-A

    Science.gov (United States)

    2011-07-26

    ... 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 1041-A, U.S. Information Return-Trust Accumulation of Charitable Amounts. DATES: Written comments... [email protected] . SUPPLEMENTARY INFORMATION: Title: U.S. Information Return-Trust...

  1. 77 FR 6827 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2012-02-09

    ... techniques or other forms of information technology. Comments to the RRB or OIRA must contain the OMB control... dollars of Last Pre- Retirement Non-Railroad Employment (LPE) earnings for each month of such service... employment with a non-railroad person, company, or institution prior to retirement, which was performed...

  2. 76 FR 45507 - Proposed Information Collection; Comment Request; Public Employment & Payroll Forms

    Science.gov (United States)

    2011-07-29

    ... Employment & Payroll Forms AGENCY: U.S. Census Bureau. ACTION: Notice. SUMMARY: The Department of Commerce... employment and payroll program which consists of an annual collection of information and a quinquennial... Public Employment & Payroll. Under Title 13, Section 161 & 182, of the United States Code, the Secretary...

  3. 75 FR 61841 - Proposed Collection; Comment Request for Forms 8804, 8804 (Sch. A), 8805 and 8813

    Science.gov (United States)

    2010-10-06

    ... Tax Payment Voucher (Section 1446). DATES: Written comments should be received on or before December 6... Information Statement of Section 1446 Withholding Tax; and Form 8813, Partnership Withholding Tax Payment Voucher 8813, Partnership Withholding Tax Payment Voucher (Section 1446). OMB Number: 1545-1119. Abstract...

  4. 78 FR 70631 - Proposed Collection; Comment Request for Forms 8804, 8804 (Sch. A), 8805 and 8813

    Science.gov (United States)

    2013-11-26

    ... Tax Payment Voucher (Section 1446). DATES: Written comments should be received on or before January 27... of Section 1446 Withholding Tax; and Form 8813, Partnership Withholding Tax Payment Voucher 8813, Partnership Withholding Tax Payment Voucher (Section 1446). OMB Number: 1545-1119. Abstract: Internal Revenue...

  5. 75 FR 3925 - Proposed Information Collection Request for Administrative Procedures-20 CFR 601 Including Form...

    Science.gov (United States)

    2010-01-25

    ... provided in the desired format, reporting burden (time and financial resources) is minimized, collection... prescribes the use of Form MA 8-7, Transmittal for Unemployment Insurance Materials. This simple check off... interested in comments that: Evaluate whether the proposed collection of information is necessary for the...

  6. 76 FR 74116 - Proposed Collection; Comment Request for Form 1127A

    Science.gov (United States)

    2011-11-30

    ..., Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form... number. Books or records relating to a collection of information must be retained as long as their contents may become material in the administration of any internal revenue law. Generally, tax returns and...

  7. 76 FR 34296 - Proposed Collection; Comment Request for Forms 1040-PR and 1040-SS

    Science.gov (United States)

    2011-06-13

    ... Form 1040-PR, Planilla para la Declaraci[oacute]n de la Contribuci[oacute]n Federal sobre el Trabajo... Trabajo por Cuenta Propia (Incluyendo el Cr[eacute]dito Tributario Adicional por Hijos para Residentes... Subtitle A, and provide credit to the taxpayer's social security account. Anejo H-PR is used to compute...

  8. 78 FR 55052 - Agency Information Collection Activities: Proposed Collection; Comment Request-Form FNS-13...

    Science.gov (United States)

    2013-09-09

    ... reporting burden hours as a result of automation and the advancement of State systems technology. The... collection techniques or other forms of information technology. Written comments may be sent to Jon Garcia... the office of the Food and Nutrition Service during regular business hours (8:30 a.m. to 5 p.m. Monday...

  9. 75 FR 49025 - Proposed Collection; Comment Request for Form W-11

    Science.gov (United States)

    2010-08-12

    ... form was developed as a template for the convenience of employers who must collect affidavits from... collection. Affected Public: Businesses or other for-profit institutions. Estimated Number of Respondents...) estimates of capital or start-up costs and costs of operation, maintenance, and purchase of services to...

  10. 78 FR 35361 - Proposed Collection; Comment Request for Form 1099-DIV

    Science.gov (United States)

    2013-06-12

    ... Actions: Five line items are added to capture state income tax information for the convenience of the...: Business or other for-profit organizations. Estimated Number of Responses: 79,134,500. Estimated Time per... forms of information technology; and (e) estimates of capital or start-up costs and costs of operation...

  11. 76 FR 62500 - Proposed Collection; Comment Request for Form 1120-F

    Science.gov (United States)

    2011-10-07

    ... comments concerning Form 1120-F, U.S. Income Tax Return of a Foreign Corporation. DATES: Written comments... Constitution Avenue, NW., Washington, DC 20224, or at (202) 622-6665, or through the Internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: U.S. Income Tax Return of a Foreign Corporation. OMB...

  12. 76 FR 56878 - Proposed Collection; Comment Request for Form 1120-REIT.

    Science.gov (United States)

    2011-09-14

    ... Form 1120-REIT, U.S. Income Tax Return for Real Estate Investment Trusts. DATES: Written comments..., 1111 Constitution Avenue, NW., Washington, DC 20224, or at (202) 927-9368, or through the Internet, [email protected] . SUPPLEMENTARY INFORMATION: Title: U.S. Income Tax Return for Real Estate...

  13. 75 FR 65678 - Agency Forms Submitted for OMB Review, Request for Comments

    Science.gov (United States)

    2010-10-26

    ... impacting editorial change to G-208 and no changes to Form G-212. The RRB estimates the completion time for... practical utility of the collections; (2) the accuracy of the estimated burden of the collections; (3) ways... (FICA) taxes be deducted from the public service wages for the last 60 months of public service...

  14. 78 FR 10001 - Proposed Collection; Comment Request for Form 706-GS(D)

    Science.gov (United States)

    2013-02-12

    ... Form 706-GS(D), Generation-Skipping Transfer Tax Return for Distributions. DATES: Written comments should be received on or before April 15, 2013 to be assured of consideration. ADDRESSES: Direct all... [email protected] . SUPPLEMENTARY INFORMATION: Title: Generation-Skipping Transfer Tax Return for...

  15. 75 FR 67164 - Proposed Collection; Comment Request for Form 8886-T

    Science.gov (United States)

    2010-11-01

    ... comments concerning Form 8886-T, Disclosure by Tax-Exempt Entity Regarding Prohibited Tax Shelter... consideration. ADDRESSES: Direct all written comments to R. Joseph Durbala, Internal Revenue Service, Room 6129... through the Internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: Disclosure by Tax...

  16. 75 FR 11995 - Proposed Collection; Comment Request for Form 706-QDT

    Science.gov (United States)

    2010-03-12

    ... Form 706-QDT, U.S. Estate Tax Return for Qualified Domestic Trusts. DATES: Written comments should be received on or before May 11, 2010 to be assured of consideration. ADDRESSES: Direct all written [email protected] . SUPPLEMENTARY INFORMATION: Title: U.S. Estate Tax Return for Qualified Domestic Trusts...

  17. Evaluating laboratory request forms submitted to haematology and blood transfusion departments at a hospital in Northwest Nigeria

    Directory of Open Access Journals (Sweden)

    Feyisayo Jegede

    2016-05-01

    Objective: We assessed routinely-submitted LRFs to determine the degree of correctness, completeness and consistency. Methods: LRFs submitted to the Department of Haematology (DH and Blood Transfusion Services (BTS of Aminu Kano Teaching Hospital in Kano, Nigeria, between October 2014 and December 2014, were evaluated for completion of all items on the forms. Performance in four quality indicator domains, including patient identifiers, test request details, laboratory details and physician details, was derived as a composite percentage. Results: Of the 2084 LRFs evaluated, 999 were from DH and 1085 from BTS. Overall, LRF completeness was 89.5% for DH and 81.2% for BTS. Information on patient name, patient location and laboratory number were 100% complete for DH, whereas only patient name was 100% complete for BTS. Incomplete information was mostly encountered on BTS forms for physician’s signature (60.8% and signature of laboratory receiver (63.5%. None of the DH and only 9.4% of BTS LRFs met all quality indicator indices. Conclusion: The level of completion of LRFs from these two departments was suboptimal. This underscores the need to review and redesign the LRF, improve on training and communication between laboratory and clinical staff and review specimen rejection practices.

  18. Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

    Directory of Open Access Journals (Sweden)

    Kristin Kassler

    2011-01-01

    Full Text Available The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4. Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120.

  19. Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

    Directory of Open Access Journals (Sweden)

    Garry Robert F

    2008-02-01

    Full Text Available Abstract Background Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. Results Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G, were established for Thogoto virus (THOV GP and Autographa california multiple NPV (AcMNPV GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. Conclusion These results suggest that proteins in the GP64 superfamily are class III penetrenes.

  20. Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

    Directory of Open Access Journals (Sweden)

    Peng Sang

    Full Text Available Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

  1. Microsoft Dynamics GP 2013 financial management

    CERN Document Server

    Grieve, Ian

    2013-01-01

    A standard tutorial-based approach covering Microsoft Dynamics GP 2013 and its six financial modules. The book is intended to allow users to improve their system use and workflow by introducing new modules to assist in financial management.This book is for you if you're a Dynamics GP partner, or Dynamics GP user, primarily focused on delivering application optimizations. This book assumes that you have a working knowledge of Microsoft Dynamics GP and have an understanding of the requirements of financial management.

  2. On πgp-continuous functions in topological spaces

    International Nuclear Information System (INIS)

    Park, Jin Han; Park, Jin Keun

    2004-01-01

    The concept of πgp-closed sets was introduced by Park [On πgp-closed sets in topological spaces, Indian J. Pure Appl. Math., in press]. The aim of this paper is to consider and characterize πgp-irresolute and πgp-continuous functions via the concept of πgp-closed sets and to relate these concepts to the classes of πGPO-compact spaces and πGP-connected spaces

  3. Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells

    DEFF Research Database (Denmark)

    Stavru, Fabrizia; Nautrup-Pedersen, Gitte; Cordes, Volker C

    2006-01-01

    So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several...... as depletion of POM121 from human fibroblasts, which do not express gp210, further suggest that NPCs can assemble or at least persist in a POM121- and gp210-free form. This points to extensive redundancies in protein-protein interactions within NPCs and suggests that vertebrate NPCs contain additional membrane...

  4. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

    DEFF Research Database (Denmark)

    Holmskov, U; Mollenhauer, J; Madsen, J

    1999-01-01

    in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine...... in a way that suggested capping, whereas other macrophages showed strong intracellular staining within the phagosome/phagolysosome compartments. In some macrophages, SP-D and gp-340 were located in the same cellular compartment. Immunoreactive gp-340 was also found in epithelial cells of the small...

  5. Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate

    DEFF Research Database (Denmark)

    Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume

    2013-01-01

    Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutr...

  6. Crystallogenesis of bacteriophage P22 tail accessory factor gp26 at acidic and neutral pH

    Energy Technology Data Exchange (ETDEWEB)

    Cingolani, Gino, E-mail: cingolag@upstate.edu; Andrews, Dewan [Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States); Casjens, Sherwood [Department of Pathology, Division of Cell Biology and Immunology, University of Utah Medical School, Salt Lake City, UT 84112 (United States); Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States)

    2006-05-01

    The crystallogenesis of bacteriophage P22 tail-fiber gp26 is described. To study possible pH-induced conformational changes in gp26 structure, native trimeric gp26 has been crystallized at acidic pH (4.6) and a chimera of gp26 fused to maltose-binding protein (MBP-gp26) has been crystallized at neutral and alkaline pH (7-10). Gp26 is one of three phage P22-encoded tail accessory factors essential for stabilization of viral DNA within the mature capsid. In solution, gp26 exists as an extended triple-stranded coiled-coil protein which shares profound structural similarities with class I viral membrane-fusion protein. In the cryo-EM reconstruction of P22 tail extracted from mature virions, gp26 forms an ∼220 Å extended needle structure emanating from the neck of the tail, which is likely to be brought into contact with the cell’s outer membrane when the viral DNA-injection process is initiated. To shed light on the potential role of gp26 in cell-wall penetration and DNA injection, gp26 has been crystallized at acidic, neutral and alkaline pH. Crystals of native gp26 grown at pH 4.6 diffract X-rays to 2.0 Å resolution and belong to space group P2{sub 1}, with a dimer of trimeric gp26 molecules in the asymmetric unit. To study potential pH-induced conformational changes in the gp26 structure, a chimera of gp26 fused to maltose-binding protein (MBP-gp26) was generated. Hexagonal crystals of MBP-gp26 were obtained at neutral and alkaline pH using the high-throughput crystallization robot at the Hauptman–Woodward Medical Research Institute, Buffalo, NY, USA. These crystals diffract X-rays to beyond 2.0 Å resolution. Structural analysis of gp26 crystallized at acidic, neutral and alkaline pH is in progress.

  7. 77 FR 38614 - Northwest Pipeline, GP; Notice of Intent To Prepare an Environmental Assessment for the Proposed...

    Science.gov (United States)

    2012-06-28

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PF12-2-000] Northwest Pipeline, GP; Notice of Intent To Prepare an Environmental Assessment for the Proposed Kalama Lateral Pipeline Project, Request for Comments on Environmental Issues, and Notice of Public Scoping Meeting The staff of the Federal Energy Regulatory Commissio...

  8. 76 FR 10348 - Northwest Pipeline, GP; Notice of Intent To Prepare an Environmental Assessment for the Proposed...

    Science.gov (United States)

    2011-02-24

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP11-59-000] Northwest Pipeline, GP; Notice of Intent To Prepare an Environmental Assessment for the Proposed Molalla Capacity Replacement Project and Request for Comments on Environmental Issues, and Notice of Public Scoping Meeting The staff of the Federal Energy Regulatory...

  9. 77 FR 41182 - Northwest Pipeline GP; Notice of Intent To Prepare an Environmental Assessment for the Proposed...

    Science.gov (United States)

    2012-07-12

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP12-471-000] Northwest Pipeline GP; Notice of Intent To Prepare an Environmental Assessment for the Proposed South Seattle Delivery Lateral Expansion Project, Request for Comments on Environmental Issues, and Notice of Public Scoping Meeting The staff of the Federal Energy...

  10. Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment

    International Nuclear Information System (INIS)

    Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

    2008-01-01

    Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS

  11. Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

    Directory of Open Access Journals (Sweden)

    Meritxell Granell

    2017-06-01

    Full Text Available Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127 punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238, while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein.

  12. 78 FR 64057 - Proposed Collection; Comment Request for Forms 1065, 1065-B, 1066, 1120, 1120-C, 1120-F, 1120-H...

    Science.gov (United States)

    2013-10-25

    ... determinants of taxpayer burden in the model are the type of entity, total assets, total receipts, and.... Income Tax Return of a Foreign Sales Corporation. Form 1120FSC (SCH P) Transfer Price or Commission. fORM... of IC-DISC Distributions. Form 1120ICD (SCH P) Intercompany Transfer Price or Commission. Form 1120IC...

  13. Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

    Science.gov (United States)

    Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.

    2013-01-01

    An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357

  14. 78 FR 36828 - Proposed Collection: Comment Request for Forms 945, 945-V, 945-A, and, 945-X

    Science.gov (United States)

    2013-06-19

    ... concerning Form 945 and 945-V, Annual Return of Withheld Federal Income Tax/ Voucher: Form 945-A Annual Record of Federal Tax Liability: Form 945-X Adjusted Annual Return of Withheld Federal Income Tax or... of consideration. ADDRESSES: Direct all written comments to Yvette Lawrence, Internal Revenue Service...

  15. Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Claudia A. Nold-Petry

    2017-12-01

    Full Text Available BackgroundThe expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.MethodsWe employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid. We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.ResultsIn the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40% and gp96-II peptide (35%. Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%, lipopolysaccharide-induced TNF (48%, IL-6 (81% and in Staphylococcus epidermidis-induced TNF (67% and IL-6 (81%, as well as IL-12/IL-18-induced IFNγ (75%. gp

  16. GPs' experiences with out-of-hours GP cooperatives: a survey study from the Netherlands.

    Science.gov (United States)

    Smits, Marleen; Keizer, Ellen; Huibers, Linda; Giesen, Paul

    2014-09-01

    Out-of-hours primary care has been provided by general practitioner (GP) cooperatives since the year 2000 in the Netherlands. Early studies in countries with similar organizational structures showed positive GP experiences. However, nowadays it is said that GPs experience a high workload at the cooperative and that they outsource a considerable part of their shifts. To examine positive and negative experiences of GPs providing out-of-hours primary care, and the frequency and reasons for outsourcing shifts. A cross-sectional observational survey among 688 GPs connected to six GP cooperatives in the Netherlands, using a web-based questionnaire. The response was 55% (n = 378). The main reasons for working in GP cooperatives were to retain registration as GP (79%) and remain experienced in acute care (74%). GPs considered the peak hours (81%) and the high number of patients (73%) as the most negative aspects. Most GPs chose to provide the out-of-hours shifts themselves: 85% outsourced maximally 25% of their shifts. The percentage of outsourced shifts increased with age. Main reasons for outsourcing were the desire to have more private time (76%); the high workload in daytime practice (71%); and less the workload during out-of-hours (46%). GPs are motivated to work in out-of-hours GP cooperatives, and they outsource few shifts. GPs consider the peak load and the large number of (non-urgent) help requests as the most negative aspects. To motivate and involve GPs for 7 × 24-h primary care, it is important to set limits on their workload.

  17. Study and preparation of 99Tcm-GP kit for lung ventilation imaging

    International Nuclear Information System (INIS)

    Zhu Lin; Meng Fanmin; Zhang Jihong; Hong Tao; Liu Yunzhong; Liu Xiujie

    1997-01-01

    The preparation of the lyophilizing reagent, D-glucose-l-phosphate (GP) kit and the method of using this kit to label 99 Tc m to form 99 Tc m -GP for lung ventilation imaging at room temperature in a simple, rapid procedure are described. The stability of the lyophilizing reagent kit under various stock conditions is examined. The results show that all of the 99 Tc m -GP yields by the lyophilizing reagent kit are above 95% at 4 degree C (cold), 20-25 degree C (room temperature) and 40 degree C (oven) for 180, 90 and 3 days, respectively. The clinical practice indicates that in comparison with 99 Tc m -DTPA, 99 Tc m -GP has remarkable difference (P 99 Tc m -GP is an ideal radioaerosol for SPECT studies of lung ventilation. It has high alveolar deposition rate but low adhesion in the major airways compared to those of 99 Tc m -DTPA. 99 Tc m -GP also features prolonged pulmonary clearance time

  18. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

    Directory of Open Access Journals (Sweden)

    Chungen Pan

    2010-02-01

    Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

  19. N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

    International Nuclear Information System (INIS)

    Dey, Antu K.; David, Kathryn B.; Ray, Neelanjana; Ketas, Thomas J.; Klasse, Per J.; Doms, Robert W.; Moore, John P.

    2008-01-01

    The native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120-gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B

  20. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication

    DEFF Research Database (Denmark)

    Meschi, Joseph; Crouch, Erika C; Skolnik, Paul

    2005-01-01

    The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL......) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate......-binding activity and was dependent on glycosylation of gp120. Native dodecameric SP-D bound to HIV gp120 more strongly than native trimeric SP-D. Since one common polymorphic form of SP-D is predominantly expressed as trimers and associated with lower blood levels, these individuals may have less effective innate...

  1. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers.

    Science.gov (United States)

    Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten; Derking, Ronald; Falkowska, Emilia; de la Peña, Alba Torrents; Cupo, Albert; Julien, Jean-Philippe; van Gils, Marit; Lee, Peter S; Peng, Wenjie; Paulson, James C; Poignard, Pascal; Burton, Dennis R; Moore, John P; Sanders, Rogier W; Wilson, Ian A; Ward, Andrew B

    2014-05-15

    All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 78 FR 32460 - Comment Request for Information Collection for ETA Form 232, Domestic Agricultural In-Season Wage...

    Science.gov (United States)

    2013-05-30

    ... Federal or State minimum wage, whichever is higher.'' The collection is also required by regulations for... legal federal or State minimum wage rate, whichever is highest unless special procedures apply to the... Collection for ETA Form 232, Domestic Agricultural In-Season Wage Report and ETA Form 232-A, Wage Survey...

  3. 75 FR 10018 - Proposed Collection; Comment Request for Form 1041 and Related Schedules D, J, and K-1

    Science.gov (United States)

    2010-03-04

    ... 1041 and Related Schedules D, J, and K-1 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION..., the IRS is soliciting comments concerning Form 1041 and related Schedules D, J, and K-1, U.S. Income...), Accumulation Distribution for Certain Complex Trusts (Schedule J), and Beneficiary's Share of Income...

  4. 78 FR 23981 - Proposed Collection; Comment Request for Form 1041 and Related Schedules D, J, and K-1

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    2013-04-23

    ... 1041 and Related Schedules D, J, and K-1 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION..., the IRS is soliciting comments concerning Form 1041 and related Schedules D, J, and K-1, U.S. Income... Losses (Schedule D), Accumulation Distribution for Certain Complex Trusts (Schedule J), and Beneficiary's...

  5. 77 FR 70545 - Proposed Collection; Comment Request; Renewal Without Change of the FinCEN Form 8300

    Science.gov (United States)

    2012-11-26

    ... information displays a valid Office of Management and Budget (OMB) control number. In accordance with 31 CFR..., Report of Cash Payments Over $10,000 Received in a Trade or Business. DATES: Written comments should be... through the Internet at www.fincen.gov/forms . SUPPLEMENTARY INFORMATION: Title: Report of Cash Payments...

  6. 75 FR 44847 - Proposed Collection; Comment Request for Forms 943, 943-PR, 943-A, and 943A-PR

    Science.gov (United States)

    2010-07-29

    ... 943, 943-PR, 943- A, and 943A-PR AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and... comments concerning Forms 943, Employer's Annual Tax Return for Agricultural Employees, 943-PR, Planilla..., Agricultural Employer's Record of Federal Tax Liability, and 943A-PR, Registro De La Obligacion Contributiva...

  7. 77 FR 50521 - Agency Information Collection Activities: Request for an Individual Fee Waiver, Form Number I-912...

    Science.gov (United States)

    2012-08-21

    ... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services [OMB Control Number 1615... Security, U.S. Citizenship and Immigration Services (USCIS) will be submitting the following information... households. The collection of information on Form I-912 is necessary in order for U.S. Citizenship and...

  8. 77 FR 73053 - Comment Request for Information Collection on Administrative Procedures Including Form MA 8-7...

    Science.gov (United States)

    2012-12-07

    ... format, reporting burden (time and financial resources) is minimized, collection instruments are clearly... prescribes the use of Form MA 8-7, Transmittal for Unemployment Insurance Materials. This simple check off... particularly interested in comments which: Evaluate whether the proposed collection of information is necessary...

  9. GP-9s are ubiquitous proteins unlikely involved in olfactory mediation of social organization in the red imported fire ant, Solenopsis invicta.

    Directory of Open Access Journals (Sweden)

    Walter S Leal

    Full Text Available The red imported fire ant (RIFA, Solenopsis invicta, is an invasive species, accidentally introduced in the United States that can cause painful (sometimes life-threatening stings to human, pets, and livestock. Their colonies have two social forms: monogyne and polygyne that have a single and multiple functional queens, respectively. A major gene (Gp-9, identified as a putative pheromone-binding protein on the basis of a modest amino acid sequence identity, has been suggested to influence the expression of colony social organization. Monogyne queens are reported to possess only the GP-9B alleles, whereas polygyne queens possess both GP-9B and GP-9b. Thus, both social forms are reported to express GP-9B, with GP-9b being a marker expressed in polygynes but it is absent in monogynes. Here, we report two types of polygyne colonies, one that does not express GP-9b (monogyne-like and the other expressing both proteins, GP-9B and GP-9b. Given their expression pattern, GP-9s are hemolymph proteins, which are more likely to be involved in the transport of lipids and small ligands within the homocoel. GP-9B existed in two forms, one of them is phosphorylated. The helical-rich content of the protein resembles the secondary structures of a beetle hemolymph protein and moth pheromone-binding proteins. An olfactory role is unlikely given the lack of specific expression in the sensillar lymph. In marked contrast to GP-9s, a chemosensory protein, SinvCSP, is demonstrated to be specifically expressed in the antennae. Within the antennae, expression of SinvCSP is restricted to the last two segments, which are known to house olfactory sensilla.

  10. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  11. Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.

    Science.gov (United States)

    Bornholdt, Zachary A; Ndungo, Esther; Fusco, Marnie L; Bale, Shridhar; Flyak, Andrew I; Crowe, James E; Chandran, Kartik; Saphire, Erica Ollmann

    2016-02-23

    The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics. Ebola virus uses its glycoprotein (GP) to enter new host cells. During entry, GP must be cleaved by human enzymes in order for receptor binding to occur. Here, we provide the crystal structure of the cleaved form of Ebola virus GP. We demonstrate that cleavage exposes a site at the top of GP and that this site binds the critical domain C of the receptor, termed Niemann-Pick C1 (NPC1). We perform mutagenesis to find parts of the site essential for binding NPC1 and map distinct roles for an upper, charged crest and lower, hydrophobic trough in cleaved GP. We find that this 3-dimensional site is conserved across the filovirus family and that antibody directed against this site is able to bind cleaved GP from every filovirus tested and neutralize viruses bearing those GPs. Copyright © 2016 Bornholdt et al.

  12. The impact of an educational intervention, the New GP Contract and NICE guidelines on anti-epilepsy therapeutic drug monitoring.

    Science.gov (United States)

    Minshall, I; Berry, D; Smith, D

    2011-03-01

    Since the early 1970s therapeutic drug monitoring (TDM) of anti-epilepsy drug (AED) levels has been available to assist in the review process of patients with epilepsy. Routine blood levels were not part of the Quality and Outcomes Framework in the New GP Contract, neither have they been generally recommended in National Guidelines (NICE and SIGN) for the management of patients with epilepsy. To assess the impact of an educational intervention, the New GP Contract and NICE guidelines on the number of requests for TDM. Retrospective study. 39 general practices serving Chester (13), the Rural area surrounding Chester (13) and Ellesmere Port (13). An educational intervention took place in the individual Chester practices between December 2001 and March 2003. For the Rural and Ellesmere Port practices there was one combined event in March 2004 and in March 2007, respectively. Practices were encouraged, not to routinely request TDM, except in certain circumstances. The number of TDM requests for Chester, Rural and Ellesmere Port were obtained from the local laboratory in Chester, plus other nearby hospitals, to provide control groups. The number of TDM requests from primary care for Chester, Rural, Ellesmere Port, Wirral, Crewe, Warrington and Wrexham, April to April, 2002 through to 2008, where available. There has been a fall in the number requests in all districts. The most significant falls were in Chester (47%), Rural (34%) and Ellesmere Port (47%), and corresponded to the time of their educational intervention. The fall has been less marked in Wirral (25%), Crewe (27%), Wrexham (10%) and Warrington (9%). In 2004, the first year after the introduction of the New GP Contract, TDM in Chester and the Rural fell significantly, while those in Ellesmere Port, Wirral, Crewe and Wrexham increased. TDM dropped significantly in Ellesmere Port in the year after their educational intervention. Despite the valproate assay being clinically unhelpful there were still 611 requests

  13. Immunization With Fc-Based Recombinant Epstein–Barr Virus gp350 Elicits Potent Neutralizing Humoral Immune Response in a BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Bingchun Zhao

    2018-05-01

    Full Text Available Epstein–Barr virus (EBV was the first human virus proved to be closely associated with tumor development, such as lymphoma, nasopharyngeal carcinoma, and EBV-associated gastric carcinoma. Despite many efforts to develop prophylactic vaccines against EBV infection and diseases, no candidates have succeeded in effectively blocking EBV infection in clinical trials. Previous investigations showed that EBV gp350 plays a pivotal role in the infection of B-lymphocytes. Nevertheless, using monomeric gp350 proteins as antigens has not been effective in preventing infection. Multimeric forms of the antigen are more potently immunogenic than monomers; however, the multimerization elements used in previous constructs are not approved for human clinical trials. To prepare a much-needed EBV prophylactic vaccine that is potent, safe, and applicable, we constructed an Fc-based form of gp350 to serve as a dimeric antigen. Here, we show that the Fc-based gp350 antigen exhibits dramatically enhanced immunogenicity compared with wild-type gp350 protein. The complete or partial gp350 ectodomain was fused with the mouse IgG2a Fc domain. Fusion with the Fc domain did not impair gp350 folding, binding to a conformation-dependent neutralizing antibody (nAb and binding to its receptor by enzyme-linked immunosorbent assay and surface plasmon resonance. Specific antibody titers against gp350 were notably enhanced by immunization with gp350-Fc dimers compared with gp350 monomers. Furthermore, immunization with gp350-Fc fusion proteins elicited potent nAbs against EBV. Our data strongly suggest that an EBV gp350 vaccine based on Fc fusion proteins may be an efficient candidate to prevent EBV infection in clinical applications.

  14. Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

    Science.gov (United States)

    Rosenberg, Steven A.; Zhai, Yifan; Yang, James C.; Schwartzentruber, Douglas J.; Hwu, Patrick; Marincola, Francesco M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Seipp, Claudia A.; Einhorn, Jan H.; Roberts, Bruce; White, Donald E.

    2008-01-01

    Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 107 and 1011 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens. PMID:9862627

  15. How Do Gut Feelings Feature in Tutorial Dialogues on Diagnostic Reasoning in GP Traineeship?

    Science.gov (United States)

    Stolper, C. F.; Van de Wiel, M. W. J.; Hendriks, R. H. M.; Van Royen, P.; Van Bokhoven, M. A.; Van der Weijden, T.; Dinant, G. J.

    2015-01-01

    Diagnostic reasoning is considered to be based on the interaction between analytical and non-analytical cognitive processes. Gut feelings, a specific form of non-analytical reasoning, play a substantial role in diagnostic reasoning by general practitioners (GPs) and may activate analytical reasoning. In GP traineeships in the Netherlands, trainees…

  16. Adaptive municipal electronic forms

    NARCIS (Netherlands)

    Kuiper, Pieternel; van Dijk, Elisabeth M.A.G.; Bondarouk, Tatiana; Ruel, Hubertus Johannes Maria; Guiderdoni-Jourdain, Karine; Oiry, Ewan

    Adaptation of electronic forms (e-forms) seems to be a step forward to reduce the burden for people who fill in forms. Municipalities more and more offer e-forms online that can be used by citizens to request a municipal product or service or by municipal employees to place a request on behalf of a

  17. Association between patients' recommendation of their GP and their evaluation of the GP.

    Science.gov (United States)

    Vedsted, Peter; Heje, Hanne N

    2008-01-01

    Patient priorities and patient evaluations indicate that accessibility should receive more attention to increase quality in general practice. The definition of family medicine emphasizes the patient-centred approach, communication skills, continuity, and clinical skills. We aimed to explore the associations between the 23 items in the Europep questionnaire measuring patient evaluation of general practice and the patients' recommendation of their general practitioner (GP) to friends and to study the relationship of these items with the core competences of family medicine. Cross-sectional study where patients aged 18 years and over attending the practice were included. Patients completed the Danish version of the 23 item Europep questionnaire and an additional item about the degree to which they could recommend their GP to friends. Danish general practice (the DanPEP study). A total of 50 191 patients and 690 GPs were included in the analyses. For each item, associations were calculated between a positive answer and the degree to which the patient could recommend the GP. Analyses were made at patient and GP levels. We found 12 items that covered the 10 most strongly associated items from both analyses: four of six items from the "doctor-patient relationship", two of five items from "medical care", and all items from "information and support" and "organization of services". No items from "accessibility" were among the 12 items. Recommending the GP to others was most strongly associated with the "emphatic", "patient-oriented", "informative and coordinating", and "competent/skilled" GP and to a lesser degree with accessibility to general practice.

  18. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

    2015-10-15

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml-1. The median IC50 of neutralized viruses was 0.033 μg ml-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

  19. Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Depetris, Rafael S.; Thomas, Antonia M.; Klasse, Per Johan; Moore, John P.

    2011-01-01

    Here, we describe the genetic pathways taken by a human immunodeficiency virus type 1 (HIV-1) isolate, D101.12, to become resistant to the small molecule CCR5 inhibitor, vicriviroc (VCV), in vitro. Resistant D101.12 variants contained at least one substitution in the gp120 V3 region (H308P), plus one of two patterns of gp41 sequence changes involving the fusion peptide (FP) and a downstream residue: G514V+V535M or M518V+F519L+V535M. Studies of Env-chimeric and point-substituted viruses in peripheral blood mononuclear cells (PBMC) and TZM-bl cells showed that resistance can arise from the cooperative action of gp120 and gp41 changes, while retaining CCR5 usage. Modeling the VCV inhibition data from the two cell types suggests that D101.12 discriminates between high- and low-VCV affinity forms of CCR5 less than D1/85.16, a resistant virus with three FP substitutions.

  20. Investigation of the function of the putative self-association site of Epstein-Barr virus (EBV) glycoprotein 42 (gp42)

    International Nuclear Information System (INIS)

    Rowe, Cynthia L.; Matsuura, Hisae; Jardetzky, Theodore S.; Longnecker, Richard

    2011-01-01

    The Epstein-Barr virus (EBV) glycoprotein 42 (gp42) is a type II membrane protein essential for entry into B cells but inhibits entry into epithelial cells. X-ray crystallography suggests that gp42 may form dimers when bound to human leukocyte antigen (HLA) class II receptor (Mullen et al., 2002) or multimerize when not bound to HLA class II (Kirschner et al., 2009). We investigated this self-association of gp42 using several different approaches. We generated soluble mutants of gp42 containing mutations within the self-association site and found that these mutants have a defect in fusion. The gp42 mutants bound to gH/gL and HLA class II, but were unable to bind wild-type gp42 or a cleavage mutant of gp42. Using purified gp42, gH/gL, and HLA, we found these proteins associate 1:1:1 by gel filtration suggesting that gp42 dimerization or multimerization does not occur or is a transient event undetectable by our methods.

  1. SHIPPING REQUESTS ON EDH

    CERN Multimedia

    Logistics Group

    2001-01-01

    Users are informed that as from 1 September 2001 all Shipping Requests must be made on EDH using the appropriate electronic form. The submission of user requests directly into EDH will help rationalise the activities of the Shipping Service (Import & Export), with requests being automatically forwarded to hierarchical supervisors thereby improving the processing speed and facilitating the follow-up. Thank you for your collaboration.

  2. Prediction of the Secondary Structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, Jan; Lund, Ole; Nielsen, Jens O.

    1996-01-01

    Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  3. 8 CFR 103.40 - Genealogical Research Requests.

    Science.gov (United States)

    2010-01-01

    .... Genealogy requests are requests for searches and/or copies of historical records relating to a deceased person, usually for genealogy and family history research purposes. (b) Manner of requesting genealogical searches and records. Requests must be submitted on Form G-1041, Genealogy Index Search Request, or Form G...

  4. General practitioner practices in requesting laboratory tests for patients with gastroenteritis in the Netherlands, 2001–2002

    Directory of Open Access Journals (Sweden)

    Koopmans Marion PG

    2006-10-01

    Full Text Available Abstract Background The objective of this study was to estimate the (selective proportion of patients consulting their GP for an episode of gastroenteritis for whom laboratory tests were requested. In addition adherence of GPs to the guidelines for diagnostic test regime was ascertained. Methods Data were collected from a GP network in the Netherlands. Information was also collected on the reason for requesting the test, test specifications, and test results. Results For 12% of the GP patients with gastroenteritis, a stool sample was requested and tested for enteric pathogens. In most patients, the duration, followed by severity of complaints or a visit to a specific, high-risk country were reported as reasons to request laboratory diagnostics. Tests were requested most often in summer months and in February. Campylobacter (requested for 87% of the tests, Salmonella (84%, Shigella (78% and Yersinia (56% were most frequently included in the stool tests. Campylobacter was detected most often in patients. Conclusion Test requests did not always comply with existing knowledge of the etiology of gastroenteritis in GP patients and were not always consistent with the Dutch GP guidelines. Therefore, the data of this study can be used to develop educational approaches for GP's as well as for revision of the guidelines.

  5. Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate.

    Science.gov (United States)

    Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume; Heyndrickx, Leo; Vanham, Guido; Jansson, Marianne; Fomsgaard, Anders; Grevstad, Berit; Ramaswamy, Meghna; Buonaguro, Franco M; Tornesello, Maria Lina; Biswas, Priscilla; Scarlatti, Gabriella; Buonaguro, Luigi

    2013-07-08

    Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity.

  6. Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

    Directory of Open Access Journals (Sweden)

    Ouyang Handong

    2011-05-01

    Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

  7. Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

    2010-03-08

    Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

  8. 77 FR 73635 - Northwest Storage GP, LLC; Notice of Application

    Science.gov (United States)

    2012-12-11

    ...) 1254 to a proposed 346-megawatt (MW) power plant located within the north industrial area of the Port...] Northwest Storage GP, LLC; Notice of Application Take notice that on November 21, 2012, Northwest Storage GP, LLC. (Northwest) filed with the Federal Energy Regulatory Commission an application under section 7 of...

  9. Internalization and Axonal Transport of the HIV Glycoprotein gp120

    Science.gov (United States)

    Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

    2015-01-01

    The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

  10. Selection for Dutch postgraduate GP training; time for improvement

    NARCIS (Netherlands)

    Vermeulen, M.I.; Kuyvenhoven, M.M.; Zuithoff, N.P.; Tromp, F.; Graaf, Y. van der; Pieters, R.H.

    2012-01-01

    Background: In the Netherlands we select candidates for the postgraduate GP training by assessing personal qualities in interviews. Because of differences in the ratio of number of candidates and number of vacancies between the eight departments of GP training we questioned whether the risk of being

  11. TRANSPORT/HANDLING REQUESTS

    CERN Multimedia

    Groupe ST/HM

    2002-01-01

    A new EDH document entitled 'Transport/Handling Request' will be in operation as of Monday, 11th February 2002, when the corresponding icon will be accessible from the EDH desktop, together with the application instructions. This EDH form will replace the paper-format transport/handling request form for all activities involving the transport of equipment and materials. However, the paper form will still be used for all vehicle-hire requests. The introduction of the EDH transport/handling request form is accompanied by the establishment of the following time limits for the various services concerned: 24 hours for the removal of office items, 48 hours for the transport of heavy items (of up to 6 metric tons and of standard road width), 5 working days for a crane operation, extra-heavy transport operation or complete removal, 5 working days for all transport operations relating to LHC installation. ST/HM Group, Logistics Section Tel: 72672 - 72202

  12. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the diagest 3-GP motivation study

    Directory of Open Access Journals (Sweden)

    Berkhout Christophe

    2012-06-01

    Full Text Available Abstract Background Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs’ attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. Methods We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs’ level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Results Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152 of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. Conclusions When a hospital-led study

  13. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the Diagest 3-GP motivation study.

    Science.gov (United States)

    Berkhout, Christophe; Vandaele-Bétancourt, Marie; Robert, Stéphane; Lespinasse, Solène; Mitha, Gamil; Bradier, Quentin; Vambergue, Anne; Fontaine, Pierre

    2012-06-21

    Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs' attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs' level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. When a hospital-led study explores issues in primary care, its design must anticipate GP

  14. Scotland's GP paediatric scholarship: an evaluation.

    Science.gov (United States)

    MacVicar, Ronald; Borland, Lyndsey; McHale, Sharon; Goh, Dayeel; Potter, Alex

    2018-05-01

    In a previous publication we described the implementation and early evaluation of general practice paediatric scholarships in Scotland. We suggested that it was too early to be able to determine whether this significant investment will produce a return for Scotland in terms of enhanced roles in providing, leading or developing children's services in primary care or at the primary care/secondary care interface. This paper presents the results of a survey of the impact of the scholarship for the first six cohorts of the scholarship (119 General Practitioners). The response rate was 76%. Of the 90 respondents, almost half (44) have developed roles or areas of special paediatric interest either within or out with the practice, or in three cases both within and out with the practice. A total of 37 (43%) of those that continue to work within general practice reported that they have developed areas of special interest of benefit to the practice. Qualitative analysis of free text questions suggested that scholars had benefited from their experience in terms of increased confidence in dealing with child health problems, developing links with secondary care colleagues, and personal gain with respect to role development. What is already known in this area: Changes in GP Training have been suggested in order to provide a workforce that can meet the needs of infants, children and young people. Studies have shown a positive impact of paediatric trainees and GP trainees learning together. Little attention has however been given to the potential to support trained GPs to develop their expertise in child health. What this work adds: Early evaluation of the Scottish Paediatric Scholarship suggested a high degree of satisfaction. This more robust evaluation suggests that almost half (44/90 respondents) have developed roles or areas of special paediatric interest either within or out with the practice, or in three cases both within and out with the practice. Suggestions for future

  15. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    International Nuclear Information System (INIS)

    Roche, Julien; Louis, John M.; Aniana, Annie; Ghirlando, Rodolfo; Bax, Ad

    2015-01-01

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion

  16. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Julien; Louis, John M.; Aniana, Annie [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States); Ghirlando, Rodolfo [National Institutes of Health, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States)

    2015-04-15

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion.

  17. Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis.

    Science.gov (United States)

    Agrawal, L; Louboutin, J-P; Reyes, B A S; Van Bockstaele, E J; Strayer, D S

    2006-12-01

    Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120 exposure, and so might be protected from ROS-mediated injury by antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1). Both enzymes detoxify oxygen free radicals. As they are highly efficient gene delivery vehicles for neurons, recombinant SV40-derived vectors were used for these studies. Cultured mature neurons derived from NT2 cells and primary fetal neurons were transduced with rSV40 vectors carrying human SOD1 and/or GPx1 cDNAs, then exposed to gp120. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Transduction efficiency of both neuron populations was >95%, as assayed by immunostaining. Transgene expression was also ascertained by Western blotting and direct assays of enzyme activity. Gp120 induced apoptosis in a high percentage of unprotected NT2-N. Transduction with SV(SOD1) and SV(GPx1) before gp120 challenge reduced neuronal apoptosis by >90%. Even greater protection was seen in cells treated with both vectors in sequence. Given singly or in combination, they protect neuronal cells from HIV-1-gp120 induced apoptosis. We tested whether rSV40 s can deliver antioxidant enzymes to the CNS in vivo: intracerebral injection of SV(SOD1) or SV(GPx1) into the caudate putamen of rat brain yielded excellent transgene expression in neurons. In vivo transduction using SV(SOD1) also protected neurons from subsequent gp120-induced apoptosis after injection of both into the caudate putamen of rat brain. Thus, SOD1 and GPx1 can be delivered by SV40 vectors in vitro or in vivo. This approach may merit consideration for

  18. The major surface glycoprotein (gp63) from Leishmania major and Leishmania donovani cleaves CD4 molecules on human T cells

    DEFF Research Database (Denmark)

    Hey, A S; Theander, T G; Hviid, L

    1994-01-01

    The effect of Leishmania major and L. donovani surface protease gp63 on surface markers on human T cells was studied using fluorescence-activated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at concentrations above 10 micrograms/ml completely inhibited binding of six different anti-CD4......-expression of CD4, reaching 50% of the initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 comparable to that seen with purified gp63. The binding of Abs directed against other surface markers present on human T-cells--CD2, CD3, CD5......, CD8, CD11A, CD25, CD45RO, CD45RA, CD58, TCR-alpha, TCR-gamma, and HLA DQ--was not inhibited by gp63. These data suggest that gp63, both in its purified form and in the form anchored to the parasite membrane, cleaves CD4 on human T cells. The cleavage of CD4 by the protease might play a role...

  19. Educational CPD: how UK GP trainers develop themselves as teachers.

    Science.gov (United States)

    Waters, Mark; Wall, David

    2007-09-01

    There is little in the literature giving the perspective of UK General Practice (GP) trainers on their development as teachers. What motivates GP trainers develop themselves as teachers? What obstacles to their professional development do GP trainers perceive? A questionnaire to all GP trainers in the West Midlands Deanery in 2004. 360/444 (81%) questionnaires were returned. 56.6% of GP trainers had another educational role in addition to training GP Registrars in the practice. 15.8% of trainers possessed an educational qualification. 13 had completed a Certificate in Medical Education and 28 were engaged in study towards that qualification. Trainers wanted more time to spend on their development as teachers than they presently have, and would then be interested in a wider variety of learning methods. However, 56.6% of trainers would still not choose to undertake a university-accredited course. Female GP trainers perceived more difficulty in obtaining protected time for their development as teachers (Educational CPD) (p = 0.021), were significantly less sure of their partners' support for this development (p = 0.033), and were more likely to agree with trainers undertaking a Certificate in Medical Education (p = 0.003). Having an additional educational role did not affect trainers' ability to take protected time, but significantly increased the amount of time aspired to (p = 0.005). Nothing made more difference to trainers' perception of their ability to undertake Educational CPD than did the perceived attitude of their partners. Educational CPD was very important to GP trainers, but getting protected time was difficult. Consideration of the needs and opinions of partners was a very strong barrier to trainers taking sufficient protected time. Given more available time, GP trainers would be more likely to consider gaining academic qualifications in education. However, this was not be something that all trainers wanted.

  20. 77 FR 20807 - Northwest Pipeline GP; Notice of Application

    Science.gov (United States)

    2012-04-06

    ... diameter pipelines away from an adjacent surface coal mine west of Kemmerer, Wyoming. Northwest also... directed to Pam Barnes, Manager Certificates and Tariffs, Northwest Pipeline GP, 295 Chipeta Way, Salt Lake...

  1. Leukemia: Derived heat shock protein gp96-peptide complex ...

    African Journals Online (AJOL)

    Jane

    2011-06-27

    Jun 27, 2011 ... Leukemia is a malignant clonal disease in hematopoietic stem cells that is typically treated with chemotherapy and radiotherapy. However ..... with autologous tumor-derived heatshock protein gp96 after liver resection for ...

  2. Sickness certification for common mental disorders and GP return-to-work advice.

    Science.gov (United States)

    Gabbay, Mark; Shiels, Chris; Hillage, Jim

    2016-09-01

    Aim To report the types and duration of sickness certification for different common mental disorders (CMDs) and the prevalence of GP advice aimed at returning the patient to work. In the United Kingdom, common mental health problems, such and depression and stress, have become the main reasons for patients requesting a sickness certificate to abstain from usual employment. Increasing attention is being paid to mental health and its impact on employability and work capacity in all parts of the welfare system. However, relatively little is known about the extent to which different mental health diagnoses impact upon sickness certification outcomes, and how the GP has used the new fit note (introduced in 2010) to support a return to work for patients with mental health diagnoses. Sickness certification data was collected from 68 UK-based general practices for a period of 12 months. Findings The study found a large part of all sickness absence certified by GPs was due to CMDs (29% of all sickness absence episodes). Females, younger patients and those living in deprived areas were more likely to receive a fit note for a CMD (compared with one for a physical health problem). The highest proportion of CMD fit notes were issued for 'stress'. However, sickness certification for depression contributed nearly half of all weeks certified for mental health problems. Only 7% of CMD fit notes included any 'may be fit' advice from the GP, with type of advice varying by mental health diagnostic category. Patients living in the most socially deprived neighbourhoods were less likely to receive 'may be fit' advice on their CMD fit notes.

  3. Exploring resilience in rural GP registrars ? implications for training

    OpenAIRE

    Walters, Lucie; Laurence, Caroline O.; Dollard, Joanne; Elliott, Taryn; Eley, Diann S.

    2015-01-01

    Background Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care pr...

  4. GP registrar well-being: a cross-sectional survey

    OpenAIRE

    Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

    2010-01-01

    Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potentia...

  5. Human immunodeficiency virus envelope protein Gp120 induces proliferation but not apoptosis in osteoblasts at physiologic concentrations.

    Directory of Open Access Journals (Sweden)

    Nathan W Cummins

    Full Text Available Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05, which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism.

  6. Selection of GP. Mur antigen-negative RBC for blood recipients with anti-'Mia ' records decreases transfusion reaction rates in Taiwan.

    Science.gov (United States)

    Yang, C-A; Lin, J-A; Chang, C-W; Wu, K-H; Yeh, S-P; Ho, C-M; Chang, J-G

    2016-10-01

    To evaluate the clinical significance of GP. Mur antigen-negative blood selection for transfusion in patients with anti-'Mi a ' records. The GP. Mur RBC phenotype is prevalent (7·3%) in Taiwan. Antibodies against GP. Mur (anti-'Mi a ') are identified in 1·24% of our population, and anti-'Mi a ' screening using GP. Mur RBC has been routine for Taiwan's blood banks. However, due to the lack of commercial antibodies, only cross-matching was used to prevent transfusion of GP. Mur-positive blood to patients with anti-'Mi a ' in most hospitals. There is still a risk of GP. Mur-positive RBC exposure and subsequent anti-'Mi a '-related transfusion reactions. Since February 2014, GP. Mur antigen-negative RBCs identified by reaction with anti-'Mi a '-positive serum were selected for blood recipients with anti-'Mi a ' records. The transfusion reactions between January 2013 and January 2014 were compared with those that occurred between February 2014 and July 2015. The transfusion reaction rate was significantly higher in anti-'Mi a '-positive blood recipients compared to total subjects receiving an RBC transfusion before GP. Mur-negative donor RBC selection. After antigen-negative RBC selection, the transfusion reaction frequency in subjects with anti-'Mi a ' became similar to total blood recipients. IgG form anti-'Mi a ' antibodies were present in all cases of probable anti-'Mi a '-related transfusion reactions. The time required for anti-'Mi a ' boosting after transfusion was around 4-21 days. Selection of GP. Mur-negative RBC for transfusion to patients with anti-'Mi a ' records could decrease the rate of transfusion reaction and antibody boosting. This procedure should be incorporated into blood bank routines in areas where anti-'Mi a ' is prevalent. © 2016 British Blood Transfusion Society.

  7. Exploring resilience in rural GP registrars--implications for training.

    Science.gov (United States)

    Walters, Lucie; Laurence, Caroline O; Dollard, Joanne; Elliott, Taryn; Eley, Diann S

    2015-07-02

    Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care providers. This study sought to explore GP registrars' perceptions of their resilience and strategies they used to maintain resilience in rural general practice. In this qualitative interpretive research, semi-structured interviews were recorded, transcribed and analysed using an inductive approach. Initial coding resulted in a coding framework which was refined using constant comparison and negative case analysis. Authors developed consensus around the final conceptual model. Eighteen GP registrars from: Australian College of Rural and Remote Medicine Independent Pathway, and three GP regional training programs with rural training posts. Six main themes emerged from the data. Firstly, rural GP registrars described four dichotomous tensions they faced: clinical caution versus clinical courage; flexibility versus persistence; reflective practice versus task-focused practice; and personal connections versus professional commitment. Further themes included: personal skills for balance which facilitated resilience including optimistic attitude, self-reflection and metacognition; and finally GP registrars recognised the role of their supervisors in supporting and stretching them to enhance their clinical resilience. Resilience is maintained as on a wobble board by balancing professional tensions within acceptable limits. These limits are unique to each individual, and may be expanded through personal growth and professional development as part of rural general practice training.

  8. Solution Structure and Membrane Interaction of the Cytoplasmic Tail of HIV-1 gp41 Protein.

    Science.gov (United States)

    Murphy, R Elliot; Samal, Alexandra B; Vlach, Jiri; Saad, Jamil S

    2017-11-07

    The cytoplasmic tail of gp41 (gp41CT) remains the last HIV-1 domain with an unknown structure. It plays important roles in HIV-1 replication such as mediating envelope (Env) intracellular trafficking and incorporation into assembling virions, mechanisms of which are poorly understood. Here, we present the solution structure of gp41CT in a micellar environment and characterize its interaction with the membrane. We show that the N-terminal 45 residues are unstructured and not associated with the membrane. However, the C-terminal 105 residues form three membrane-bound amphipathic α helices with distinctive structural features such as variable degree of membrane penetration, hydrophobic and basic surfaces, clusters of aromatic residues, and a network of cation-π interactions. This work fills a major gap by providing the structure of the last segment of HIV-1 Env, which will provide insights into the mechanisms of Gag-mediated Env incorporation as well as the overall Env mobility and conformation on the virion surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. How international medical graduates view their learning needs for UK GP training.

    Science.gov (United States)

    Warwick, Christopher

    2014-03-01

    International medical graduates (IMGs) form a vital group of general practitioners (GPs) in the NHS. They are known to face additional challenges above and beyond those faced by UK medical graduates in the course of their GP training. Whilst they are a heterogeneous group of professionals, their views on what they need to learn, and how they are supported, are often distant from those of the educators responsible for planning their education. This study was undertaken, through narrative-based focus groups, to explore the issues which matter to the IMGs, in an attempt to empower their voices about their experiences in GP training, and to see what lessons could be drawn from these views. The findings confirmed the central importance, and considerable challenge involved, in making an effective transition into the culture of the NHS and UK general practice. The IMGs felt that induction needed to be an on-going, iterative process of learning which continued throughout training, with a more effective individualised learning needs analysis at the start of GP training. Lack of sophisticated language skills was highlighted as a real concern. Recognition that their lack of knowledge about the NHS at the start of training should not be seen as an indicator of deficiency, but a clue to what they needed to learn were also key messages. IMGs also felt the earlier in their training they undertook a GP placement, the quicker they would start to understand the culture of general practice in the UK. Further work following on from this research should include how to manage change in the educational network for these barriers to be overcome.

  10. Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.

    Directory of Open Access Journals (Sweden)

    Lijun Chao

    Full Text Available The HIV-1 envelope glycoprotein (Env gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no, immunogenicity to humans. Here, we found that the C-terminal fragment (aa 462-521 of the human POB1 (the partner of RalBP1, designated C60, is an HIV-1 fusion inhibitor. It bound to N36, the peptide derived from the N-terminal heptad repeat (NHR of gp41, and to the six-helix bundle (6-HB formed by N36 and C34, a CHR-peptide, but it did not bind to C34. Unlike the CHR-peptides, C60 did not block gp41 6-HB formation. Rather, results suggest that C60 inhibits HIV-1 fusion by binding to the 6-HB, in particular, the residues in the gp41 NHR domain that are exposed on the surface of 6-HB. Since 6-HB plays a crucial role in the late stage of fusion between the viral envelope and endosomal membrane during the endocytic process of HIV-1, C60 may serve as a host restriction factor to suppress HIV-1 entry into CD4+ T lymphocytes. Taken together, it can be concluded from these results that C60 can be used as a lead for the development of anti-HIV-1 therapeutics or microbicides for the treatment and prevention of HIV-1 infection, as well as a molecular probe to study the fusogenic mechanism of HIV-1.

  11. 78 FR 20139 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Request for...

    Science.gov (United States)

    2013-04-03

    ... Collection; Comments Requested: Request for Recognition of a Non-profit Religious, Charitable, Social Service... Approved Collection. (2) Title of the Form/Collection: Request for Recognition of a Non- profit Religious, Charitable, Social Service, or Similar Organization. (3) Agency form number, if any, and the applicable...

  12. 78 FR 36577 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Request for...

    Science.gov (United States)

    2013-06-18

    ... Collection; Comments Requested: Request for Recognition of a Non-Profit Religious, Charitable, Social Service... Collection. (2) Title of the Form/Collection: Request for Recognition of a Non- profit Religious, Charitable, Social Service, or Similar Organization. (3) Agency form number, if any, and the applicable component of...

  13. Patient influences on satisfaction and loyalty for GP services.

    Science.gov (United States)

    Rundle-Thiele, Sharyn; Russell-Bennett, Rebekah

    2010-04-01

    Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centered care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

  14. 12 CFR 404.4 - Request requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Request requirements. 404.4 Section 404.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.4 Request requirements. (a) Form. Requests...

  15. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

  17. Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial.

    Science.gov (United States)

    Agnandji, Selidji T; Fernandes, José F; Bache, Emmanuel B; Obiang Mba, Régis M; Brosnahan, Jessica S; Kabwende, Lumeka; Pitzinger, Paul; Staarink, Pieter; Massinga-Loembe, Marguerite; Krähling, Verena; Biedenkopf, Nadine; Fehling, Sarah Katharina; Strecker, Thomas; Clark, David J; Staines, Henry M; Hooper, Jay W; Silvera, Peter; Moorthy, Vasee; Kieny, Marie-Paule; Adegnika, Akim A; Grobusch, Martin P; Becker, Stephan; Ramharter, Michael; Mordmüller, Benjamin; Lell, Bertrand; Krishna, Sanjeev; Kremsner, Peter G

    2017-10-01

    The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280-1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine

  18. Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial.

    Directory of Open Access Journals (Sweden)

    Selidji T Agnandji

    2017-10-01

    Full Text Available The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU in a trial in Guinea. This study provides further safety and immunogenicity data.A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV-glycoprotein (GP-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908, 556 (95% CI: 280-1,101, 1,245 (95% CI: 899-1,724, and 1,503 (95% CI: 931-2,426, respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591, 1,887 (1,154-3,085, 1,445 (1,013-2,062, and 3,958 (2,249-6,967 for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The

  19. 24 CFR 15.109 - How will HUD respond to a request for information from Form HUD-92410 (Statement of Profit and...

    Science.gov (United States)

    2010-04-01

    ... with their investment decision. (c) To whom may potential investors disclose such information... for information from Form HUD-92410 (Statement of Profit and Loss)? 15.109 Section 15.109 Housing and... Form HUD-92410 (Statement of Profit and Loss)? (a) To whom will HUD disclose the information? HUD will...

  20. 78 FR 63570 - Proposed Collection; Comment Request for Forms W-8BEN, W-8BEN-E, W-8ECI, W-8EXP, and W-8IMY

    Science.gov (United States)

    2013-10-24

    ... W-8BEN, W-8BEN-E, W-8ECI, W-8EXP, and W-8IMY AGENCY: Internal Revenue Service (IRS), Treasury..., the IRS is soliciting comments concerning Form W-8BEN, Certificate of Foreign Status of Beneficial Owner for United States Tax Withholding, Form W-8BEN-E, Certificate of Status of Beneficial Owner for...

  1. 75 FR 38179 - Proposed Collection; Comment Request for Forms W-8BEN, W-8ECI, W-8EXP, and W-8IMY

    Science.gov (United States)

    2010-07-01

    ... W-8BEN, W-8ECI, W- 8EXP, and W-8IMY AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice... soliciting comments concerning Form W-8BEN, Certificate of Foreign Status of Beneficial Owner for United States Tax Withholding, Form W-8ECI, Certificate of Foreign Person's Claim for Exemption From Withholding...

  2. Optional part-time and longer GP training modules in GP practices associated with more trainees becoming GPs - a cohort study in Switzerland.

    Science.gov (United States)

    Studerus, Lara; Ahrens, Regina; Häuptle, Christian; Goeldlin, Adrian; Streit, Sven

    2018-01-05

    Switzerland, like many other countries, has a shortage of General Practitioners (GPs). Optional GP training modules in GP practices were offered during the at least 5-year GP training program to increase student and trainee interest in becoming a GP. The training modules had not yet been evaluated. We determined how many Swiss GP trainees became practicing GPs after they completed optional training modules, and if longer modules were associated with higher rates of GP specialization. In this population-based cohort study, we included GP trainees who chose an optional GP training module in GP practice, provided by the Foundation to Promote Training in General Practice (WHM) between 2006 and 2015. GP trainees were invited to complete an online survey to assess the primary outcome (becoming a practicing GP by 2016). Data on non-responders was collected via an internet search. We calculated univariate time-to-event curves to become a practicing GP, stratified by trainee's gender, length, part-time training, and number of years after graduation until training modules were completed. We used a multivariate model to adjust for characteristics of participants, training, and satisfaction with training modules. We assessed primary outcome for 351 (92.1%) of 381 former GP trainees who participated in a WHM program between 2006 and 2015. Of these 218 (57%) were practicing GPs by 2016. When focusing on the trainees who had completed training between 2006 and 2010, the rate of practicing GPs was even 73%. Longer (p = 0.018) and part-time training modules (p = 0.003) were associated with higher rates of being a practicing GP. Most (81%) practicing GPs thought their optional GP training module was (very) important in their choice of specialty. GP trainees who spent more time training in a GP practice, or who trained part-time were more likely to become practicing GPs. Most (80%) rated their training module as (very) important in their choice of career, highlighting that

  3. Potable Water Treatment Facility General Permit (PWTF GP) ...

    Science.gov (United States)

    2017-08-28

    The Final PWTF GP establishes permit eligibility conditions, Notice of Intent (NOI) requirements, effluent limitations, standards, prohibitions, and best management practices for facilities that discharge to waters in the Commonwealth of Massachusetts (including both Commonwealth and Indian country lands) and the State of New Hampshire.

  4. GP registrar well-being: a cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Schattner Peter

    2010-02-01

    Full Text Available Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS, a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Results Survey response rate of 51% (102/199. Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS and 7% mild to moderately anxious (DASS. Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors; similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. Conclusions This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

  5. Do practice nurse solve future GP capacity problems?

    NARCIS (Netherlands)

    Lamkaddem, M.; Haan, J. de; Bakker, D. de

    2003-01-01

    Background: Task delegation is viewed as an important policy instrument to counter foreseen future shortages in GP capacity in the Netherlands. Therefore, a national programme to introduce practice nurses in general practice was launched in 1998 by the National Association of General Practice. In

  6. GP registrar well-being: a cross-sectional survey.

    Science.gov (United States)

    Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

    2010-02-09

    To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Survey response rate of 51% (102/199). Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS) and 7% mild to moderately anxious (DASS). Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors); similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

  7. Blended learning in CME: the perception of GP trainers

    NARCIS (Netherlands)

    te Pas, E.; Meinema, J. G.; Visser, M. R. M.; van Dijk, N.

    2016-01-01

    Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical

  8. Assessment of reliability of Greulich and Pyle (gp) method for ...

    African Journals Online (AJOL)

    Background: Greulich and Pyle standards are the most widely used age estimation standards all over the world. The applicability of the Greulich and Pyle standards to populations which differ from their reference population is often questioned. This study aimed to assess the reliability of Greulich and Pyle (GP) method for ...

  9. Crystal structure of an EAL domain in complex with reaction product 5'-pGpG.

    Directory of Open Access Journals (Sweden)

    Julien Robert-Paganin

    Full Text Available FimX is a large multidomain protein containing an EAL domain and involved in twitching motility in Pseudomonas aeruginosa. We present here two crystallographic structures of the EAL domain of FimX (residues 438-686: one of the apo form and the other of a complex with 5'-pGpG, the reaction product of the hydrolysis of c-di-GMP. In both crystal forms, the EAL domains form a dimer delimiting a large cavity encompassing the catalytic pockets. The ligand is trapped in this cavity by its sugar phosphate moiety. We confirmed by NMR that the guanine bases are not involved in the interaction in solution. We solved here the first structure of an EAL domain bound to the reaction product 5'-pGpG. Though isolated FimX EAL domain has a very low catalytic activity, which would not be significant compared to other catalytic EAL domains, the structure with the product of the reaction can provides some hints in the mechanism of hydrolysis of the c-di-GMP by EAL domains.

  10. Crystal structure of an EAL domain in complex with reaction product 5'-pGpG.

    Science.gov (United States)

    Robert-Paganin, Julien; Nonin-Lecomte, Sylvie; Réty, Stéphane

    2012-01-01

    FimX is a large multidomain protein containing an EAL domain and involved in twitching motility in Pseudomonas aeruginosa. We present here two crystallographic structures of the EAL domain of FimX (residues 438-686): one of the apo form and the other of a complex with 5'-pGpG, the reaction product of the hydrolysis of c-di-GMP. In both crystal forms, the EAL domains form a dimer delimiting a large cavity encompassing the catalytic pockets. The ligand is trapped in this cavity by its sugar phosphate moiety. We confirmed by NMR that the guanine bases are not involved in the interaction in solution. We solved here the first structure of an EAL domain bound to the reaction product 5'-pGpG. Though isolated FimX EAL domain has a very low catalytic activity, which would not be significant compared to other catalytic EAL domains, the structure with the product of the reaction can provides some hints in the mechanism of hydrolysis of the c-di-GMP by EAL domains.

  11. Managerialism and the British GP: the GP as manager and as managed.

    Science.gov (United States)

    Warwicker, T

    1998-01-01

    The focus of the paper is on the relationship between General Practitioners (GPs) and central government. This relationship dates from the introduction of national health insurance in the UK. From the outset it had an impact on GPs' medical role, their professional status and income. The structure created in 1911 meant that GPs operated as franchisees and, notwithstanding Labour's policy objective of creating a salaried service, this role continued, effectively unchanged, after the creation of the National Health Service (NHS) in 1948. General practice was also the poor relation in contrast to hospital medicine, a feature intensified by the priorities of the NHS. These forces meant that GPs had a dual role: that of clinician and gatekeeper to specialist hospital services, a role in which they exercised substantial clinical freedom: and running a small business, a feature which was exaggerated by the absence of grant aid to improve premises prior to the Family Doctor Charter of 1965. This structural relationship has been progressively transformed by changes in the 1980s and 1990s. On the one hand the emphasis on cost control has seen central government attempting to combine a financial with a clinical gate-keeping keeping role. The crucial change in this respect is the creation of GP fundholding which, in turn, could be seen to have implications for the subordinate status of GPs within the medical profession. However, this has been combined with trends to greater measures of control over GPs. Of central importance in this respect were the changes introduced by the 1990 GP contract. The contract involved an attempt to substantially reduce clinical autonomy by building in much more detailed contractual duties with respect, for example, to health promotion activities. This was combined with the use of financial incentives to reach, for example, immunization targets. Control over clinical autonomy has also involved constraints over prescribing and the shift from Family

  12. CGP lil-gp 2.1;1.02 User's Manual

    Science.gov (United States)

    Janikow, Cezary Z.; DeWeese, Scott W.

    1997-01-01

    This document describes extensions provided to lil-gp facilitating dealing with constraints. This document deals specifically with lil-gp 1.02, and the resulting extension is referred to as CGP lil-gp 2.1; 1.02 (the first version is for the extension, the second for the utilized lil-gp version). Unless explicitly needed to avoid confusion, version numbers are omitted.

  13. General practitioner views on the determinants of test ordering: a theory-based qualitative approach to the development of an intervention to improve immunoglobulin requests in primary care.

    LENUS (Irish Health Repository)

    Cadogan, S L

    2016-07-19

    Research suggests that variation in laboratory requesting patterns may indicate unnecessary test use. Requesting patterns for serum immunoglobulins vary significantly between general practitioners (GPs). This study aims to explore GP\\'s views on testing to identify the determinants of behaviour and recommend feasible intervention strategies for improving immunoglobulin test use in primary care.

  14. 77 FR 25196 - Agency Information Collection Activities: Proposed Collection; Comments Requested; Request for...

    Science.gov (United States)

    2012-04-27

    ... Collection; Comments Requested; Request for Recognition of a Non-Profit Religious, Charitable, Social Service...) Title of the Form/Collection: Request for Recognition of a Non- profit Religious, Charitable, Social... organization meets the regulatory and relevant case law requirements for recognition by the Board as a legal...

  15. Attitudes towards obesity treatment in GP training practices: a focus group study

    NARCIS (Netherlands)

    Jochemsen-van der Leeuw, H. G. A.; van Dijk, N.; Wieringa-de Waard, M.

    2011-01-01

    Both patients and government expect the GP to treat obesity. Previous studies reported a negative attitude of GPs towards this task. Little is known about the attitude of GP trainees. To assess the attitude and other factors that influence the willingness and ability of GP trainees to provide

  16. Why are some patients in treatment for advanced cancer reluctant to consult their GP?

    DEFF Research Database (Denmark)

    Åbom, Birgit; Pfeiffer, Per

    2009-01-01

    and therefore consulted the doctor or the staff at the cancer treatment centre before seeking advice from their GP. Some patients found that the GP was not familiar enough with the treatments given; others that they did not want to inconvenience the busy GP with what they perceived to be minor non...

  17. Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

    Energy Technology Data Exchange (ETDEWEB)

    Arulanandam, Rozanne; Geletu, Mulu [Departments of Microbiology and Immunology and Pathology and Molecular Medicine, and Queen' s University Cancer Institute, Queen' s University, Botterell Hall, Rm. 713, Kingston, Ontario, Canada K7L 3N6 (Canada); Feracci, Helene [Universite Bordeaux 1, Centre de Recherche Paul Pascal, CNRS UPR 8641, 33600 Pessac (France); Raptis, Leda, E-mail: raptisl@queensu.ca [Departments of Microbiology and Immunology and Pathology and Molecular Medicine, and Queen' s University Cancer Institute, Queen' s University, Botterell Hall, Rm. 713, Kingston, Ontario, Canada K7L 3N6 (Canada)

    2010-03-10

    Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac{sup V12}), at different cell densities. The results revealed for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac{sup V12} with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac{sup V12}-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac{sup V12} is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac{sup V12} expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac{sup V12}. The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac{sup V12}, as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.

  18. Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

    International Nuclear Information System (INIS)

    Arulanandam, Rozanne; Geletu, Mulu; Feracci, Helene; Raptis, Leda

    2010-01-01

    Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac V12 ), at different cell densities. The results revealed for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac V12 with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac V12 -expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac V12 is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac V12 expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac V12 . The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac V12 , as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.

  19. Lessons learned from an Internet GP information system.

    Science.gov (United States)

    Briggs, J S; Bradley, M P

    1998-01-01

    We describe the prototype of an application that in actual use would allow GPs to find out more information about consultants at hospitals. This would aid the GP in making the decision about which consultant a patient should be referred to. The requirements of the application from the GP's perspective are described, together with some of the issues that have to be resolved before hospitals can provide the necessary information in a standard format. The application is implemented as a client--server system using standard Internet technologies such as Java and HTML. This architecture has a number of advantages but also revealed some issues concerning security and the format of data, among other things. The project showed that there is a desire for such a system and that that desire can be fulfilled at a relatively low cost.

  20. HIV-gp120 and physical dependence to buprenorphine.

    Science.gov (United States)

    Palma, J; Abood, M E; Benamar, K

    2015-05-01

    Opioids are among the most effective and commonly used analgesics in clinical practice for severe pain. However, the use of opioid medications is clinically limited by several adverse properties including dependence. While opioid dependence is a complex health condition, the treatment of HIV-infected individuals with opioid dependence presents additional challenges. The goal of this study was to examine the physical dependence to buprenorphine in the context of HIV. Young adult male rats (Sprague-Dawley) were pretreated with HIV-1 envelope glycoprotein 120 (gp120) injected into the periaqueductal gray area (PAG) and we examined the impact on physical dependence to opioid. It was found that the physical dependence to methadone occurred earlier than that to buprenorphine, and that gp120 did not enhance or precipitate the buprenorphine withdrawal. The results suggest that buprenorphine could be the better therapeutic option to manage opioid dependence in HIV. Copyright © 2015. Published by Elsevier Ireland Ltd.

  1. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  2. Blended learning in CME: the perception of GP trainers.

    Science.gov (United States)

    Te Pas, E; Meinema, J G; Visser, M R M; van Dijk, N

    2016-05-01

    Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

  3. GP140/CDCPI in the Development of Prostate Cancer Metastasis

    Science.gov (United States)

    2013-09-01

    localization of Gp140 to the plasma membrane of prostate epithelial cells is decreased or lost in PIN, invasive and metastatic prostate cancers when...Matrigel (BD Biosciences, Franklin Lakes, NJ) at 2000 cells per well. Spheroid structures were extracted and expanded in regu- lar tissue culture, and...cell surface (Figure 2A). Some surface-negative cells express E-cadherin in the cytoplasm. Cells were cultured in Matrigel, and spheroid structures

  4. Basket Option Pricing Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.

    2010-08-01

    We introduce a basket option pricing problem arisen in financial mathematics. We discretized the problem based on the alternating direction implicit (ADI) method and parallel cyclic reduction is applied to solve the set of tridiagonal matrices generated by the ADI method. To reduce the computational time of the problem, a general purpose graphics processing units (GP-GPU) environment is considered. Numerical results confirm the convergence and efficiency of the proposed method. © 2010 IEEE.

  5. Membrane topology analysis of HIV-1 envelope glycoprotein gp41

    Directory of Open Access Journals (Sweden)

    Xiao Dan

    2010-11-01

    Full Text Available Abstract Background The gp41 subunit of the HIV-1 envelope glycoprotein (Env has been widely regarded as a type I transmembrane protein with a single membrane-spanning domain (MSD. An alternative topology model suggested multiple MSDs. The major discrepancy between the two models is that the cytoplasmic Kennedy sequence in the single MSD model is assigned as the extracellular loop accessible to neutralizing antibodies in the other model. We examined the membrane topology of the gp41 subunit in both prokaryotic and mammalian systems. We attached topological markers to the C-termini of serially truncated gp41. In the prokaryotic system, we utilized a green fluorescent protein (GFP that is only active in the cytoplasm. The tag protein (HaloTag and a membrane-impermeable ligand specific to HaloTag was used in the mammalian system. Results In the absence of membrane fusion, both the prokaryotic and mammalian systems (293FT cells supported the single MSD model. In the presence of membrane fusion in mammalian cells (293CD4 cells, the data obtained seem to support the multiple MSD model. However, the region predicted to be a potential MSD is the highly hydrophilic Kennedy sequence and is least likely to become a MSD based on several algorithms. Further analysis revealed the induction of membrane permeability during membrane fusion, allowing the membrane-impermeable ligand and antibodies to cross the membrane. Therefore, we cannot completely rule out the possible artifacts. Addition of membrane fusion inhibitors or alterations of the MSD sequence decreased the induction of membrane permeability. Conclusions It is likely that a single MSD model for HIV-1 gp41 holds true even in the presence of membrane fusion. The degree of the augmentation of membrane permeability we observed was dependent on the membrane fusion and sequence of the MSD.

  6. Impact of Leishmania metalloprotease GP63 on macrophage signaling

    Science.gov (United States)

    Isnard, Amandine; Shio, Marina T.; Olivier, Martin

    2012-01-01

    The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions. PMID:22919663

  7. Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

    Science.gov (United States)

    Cai, Lifeng; Gochin, Miriam; Liu, Keliang

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

  8. 78 FR 64293 - Proposed Collection; Comment Request

    Science.gov (United States)

    2013-10-28

    ... Investment Companies. OMB Number: 1545-1010. Form Number: 1120-RIC. Abstract: Internal Revenue Code sections... DEPARTMENT OF THE TREASURY Internal Revenue Service [Form 1120-RIC] Proposed Collection; Comment Request AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments. SUMMARY...

  9. GP's consult and health behaviour change project. Developing a programme to train GPs in communication skills to achieve lifestyle improvements.

    Science.gov (United States)

    Thijs, G A

    2007-08-01

    The European definition of General Practice states that GPs should use their core competence, amongst others, in their communication with patients. Their communication skills are particularly challenged in the field of lifestyle improvements. Most GPs feel they lack efficacy in achieving lifestyle changes. In November 2002 the Prevention Department of the Scientific Society of Flemish GPs (now Domus Medica) decided to start a project "consulting & behaviour change". Under this project, every Flemish GP should by the year 2007, have (amongst others things) a basic knowledge of the principles of lifestyle improvements and should be able to give a short advice to high risk patients. A literature search was conducted to make an inventory of models that could be used to train GPs. Experts at specific methods and topics were consulted to get acquainted with their specific approaches. Experts in the field of CME were gathered to discuss barriers and solutions to these barriers. During steering group meetings, several possible solutions were discussed. The Trans Theoretical Model (TTM-as theoretical framework) and brief motivational interviews (MI-as communication skill) were evaluated as offering the best opportunities for adapting the work situation of the GP. We promoted this approach to the GPs as an ABC concept (Anamnesis/Ask; Be the guide/Decision tree ("Beslissingsboom" in Dutch); Continuity) applied on different topics (smoke stop, alcohol, healthy food, physical activity). In our guidelines we pay more attention to brief motivational interviews for health behaviour changes. Recently we started developing an e-learning website as part of a larger learning project, this in cooperaion with different Flemish partners and disciplines. The Trans Theoretical Model and the brief motivational interviewing approach seem to be accepted by health care, educational and scientific organisations. The process of integrating this approach in the GP's daily practice has to be

  10. Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial

    NARCIS (Netherlands)

    Agnandji, Selidji T.; Fernandes, José F.; Bache, Emmanuel B.; Obiang Mba, Régis M.; Brosnahan, Jessica S.; Kabwende, Lumeka; Pitzinger, Paul; Staarink, Pieter; Massinga-Loembe, Marguerite; Krähling, Verena; Biedenkopf, Nadine; Fehling, Sarah Katharina; Strecker, Thomas; Clark, David J.; Staines, Henry M.; Hooper, Jay W.; Silvera, Peter; Moorthy, Vasee; Kieny, Marie-Paule; Adegnika, Akim A.; Grobusch, Martin P.; Becker, Stephan; Ramharter, Michael; Mordmüller, Benjamin; Lell, Bertrand; Krishna, Sanjeev; Kremsner, Peter G.

    2017-01-01

    The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 ×

  11. Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL to maraviroc.

    Directory of Open Access Journals (Sweden)

    Yuzhe Yuan

    Full Text Available Maraviroc, an (HIV-1 entry inhibitor, binds to CCR5 and efficiently prevents R5 human immunodeficiency virus type 1 (HIV-1 from using CCR5 as a coreceptor for entry into CD4(+ cells. However, HIV-1 can elude maraviroc by using the drug-bound form of CCR5 as a coreceptor. This property is known as noncompetitive resistance. HIV-1(V3-M5 derived from HIV-1(JR-FLan is a noncompetitive-resistant virus that contains five mutations (I304V/F312W/T314A/E317D/I318V in the gp120 V3 loop alone. To obtain genetic and structural insights into maraviroc resistance in HIV-1, we performed here mutagenesis and computer-assisted structural study. A series of site-directed mutagenesis experiments demonstrated that combinations of V3 mutations are required for HIV-1(JR-FLan to replicate in the presence of 1 µM maraviroc, and that a T199K mutation in the C2 region increases viral fitness in combination with V3 mutations. Molecular dynamic (MD simulations of the gp120 outer domain V3 loop with or without the five mutations showed that the V3 mutations induced (i changes in V3 configuration on the gp120 outer domain, (ii reduction of an anti-parallel β-sheet in the V3 stem region, (iii reduction in fluctuations of the V3 tip and stem regions, and (iv a shift of the fluctuation site at the V3 base region. These results suggest that the HIV-1 gp120 V3 mutations that confer maraviroc resistance alter structure and dynamics of the V3 loop on the gp120 outer domain, and enable interactions between gp120 and the drug-bound form of CCR5.

  12. Induction of HIV neutralizing antibodies against the MPER of the HIV envelope protein by HA/gp41 chimeric protein-based DNA and VLP vaccines.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14 in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy.

  13. Conceptualising GP teachers' knowledge: a pedagogical content knowledge perspective.

    Science.gov (United States)

    Cantillon, Peter; de Grave, Willem

    2012-05-01

    Most teacher development initiatives focus on enhancing knowledge of teaching (pedagogy), whilst largely ignoring other important features of teacher knowledge such as subject matter knowledge and awareness of the learning context. Furthermore, teachers' ability to learn from faculty development interventions is limited by their existing (often implicit) pedagogical knowledge and beliefs. Pedagogical content knowledge (PCK) represents a model of teacher knowledge incorporating what they know about subject matter, pedagogy and context. PCK can be used to explore teachers' prior knowledge and to structure faculty development programmes so that they take account of a broader range of teachers' knowledge. We set out to examine the application of a PCK model in a general practice education setting. This study is part of a larger study that employed a mixed method approach (concept mapping, phenomenological interviews and video-stimulated recall) to explore features of GP teachers' subject matter knowledge, pedagogical knowledge and knowledge of the learning environment in the context of a general practice tutorial. This paper presents data on GP teachers' pedagogical and context knowledge. There was considerable overlap between different GP teachers' knowledge and beliefs about learners and the clinical learning environment (i.e. knowledge of context). The teachers' beliefs about learners were largely based on assumptions derived from their own student experiences. There were stark differences, however, between teachers in terms of pedagogical knowledge, particularly in terms of their teaching orientations (i.e. transmission or facilitation orientation) and this was manifest in their teaching behaviours. PCK represents a useful model for conceptualising clinical teacher prior knowledge in three domains, namely subject matter, learning context and pedagogy. It can and should be used as a simple guiding framework by faculty developers to inform the design and delivery of

  14. The GP problem: quantifying gene-to-phenotype relationships.

    Science.gov (United States)

    Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

    2002-01-01

    In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

  15. Parallelized Local Volatility Estimation Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.

    2010-01-01

    We introduce an inverse problem for the local volatility model in option pricing. We solve the problem using the Levenberg-Marquardt algorithm and use the notion of the Fréchet derivative when calculating the Jacobian matrix. We analyze the existence of the Fréchet derivative and its numerical computation. To reduce the computational time of the inverse problem, a GP-GPU environment is considered for parallel computation. Numerical results confirm the validity and efficiency of the proposed method. ©2010 IEEE.

  16. Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

    Directory of Open Access Journals (Sweden)

    Valeria Feinshtein

    2013-09-01

    Full Text Available Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD, a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp and Breast Cancer Resistance Protein (BCRP expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp for comparison. Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3 and rhodamine123(rh123. Cyclosporine A (CsA served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3 and rh123 was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

  17. An alternative conformation of the gp41 heptad repeat 1 region coiled coil exists in the human immunodeficiency virus (HIV-1) envelope glycoprotein precursor

    International Nuclear Information System (INIS)

    Mische, Claudia C.; Yuan Wen; Strack, Bettina; Craig, Stewart; Farzan, Michael; Sodroski, Joseph

    2005-01-01

    The human immunodeficiency virus (HIV-1) transmembrane envelope glycoprotein, gp41, which mediates virus-cell fusion, exists in at least three different conformations within the trimeric envelope glycoprotein complex. The structures of the prefusogenic and intermediate states are unknown; structures representing the postfusion state have been solved. In the postfusion conformation, three helical heptad repeat 2 (HR2) regions pack in an antiparallel fashion into the hydrophobic grooves on the surface of a triple-helical coiled coil formed by the heptad repeat 1 (HR1) regions. We studied the prefusogenic conformation of gp41 by mutagenic alteration of membrane-anchored and soluble forms of the HIV-1 envelope glycoproteins. Our results indicate that, in the HIV-1 envelope glycoprotein precursor, the gp41 HR1 region is in a conformation distinct from that of a trimeric coiled coil. Thus, the central gp41 coiled coil is formed during the transition of the HIV-1 envelope glycoproteins from the precursor state to the receptor-bound intermediate

  18. Shuttle requests

    CERN Multimedia

    2007-01-01

    Please note that starting from 1 March 2007, the shuttle requests: for official visits or bidders' conferences on the CERN site; towards/from the airport or central Geneva; for long distances, shall be made via Fm.Support@cern.ch or by calling 77777. The radio taxi will still be reachable at 76969. TS/FM Group

  19. Payment mechanism and GP self-selection: capitation versus fee for service.

    Science.gov (United States)

    Allard, Marie; Jelovac, Izabela; Léger, Pierre-Thomas

    2014-06-01

    This paper analyzes the consequences of allowing gatekeeping general practitioners (GPs) to select their payment mechanism. We model GPs' behavior under the most common payment schemes (capitation and fee for service) and when GPs can select one among them. Our analysis considers GP heterogeneity in terms of both ability and concern for their patients' health. We show that when the costs of wasteful referrals to costly specialized care are relatively high, fee for service payments are optimal to maximize the expected patients' health net of treatment costs. Conversely, when the losses associated with failed referrals of severely ill patients are relatively high, we show that either GPs' self-selection of a payment form or capitation is optimal. Last, we extend our analysis to endogenous effort and to competition among GPs. In both cases, we show that self-selection is never optimal.

  20. A study into the effectiveness of unqualified GP assistants.

    Science.gov (United States)

    Philip, Marilyn; Turnbull, Betty

    This article aims to address the potential shortfall in care provision offered by general practitioners (GPs) resulting from pending retirement and the retention and recruitment crisis. An educational module was developed that offered both theory and practise to unqualified general practice assistants. The module content was determined following discussion with local GPs. A small qualitative study of six students was carried out to review efficacy of participants in their new role. Using a grounded theory approach, participant and supervisor views of course content and delivery, role preparation diversity were analysed and compared. Tape-recorded interviews were conducted and analysis carried out employing the constant comparative method. Data were coded and emergent themes categorized. Overall, participants agreed that the module had strengthened their knowledge, added new skills, heightened their job satisfaction, added significant diversity to their role and enhanced their employability potential. Five participants communicated that they were more confident in performing clinical skills and advising health improvement techniques. Supervisors also reported that participants displayed a more competent and professional approach to health care, which was complementary to the role of the GP and practice nurse. Ultimately this allowed both GP and practice nurse to focus on dealing with chronic illness targets, as required in the new directive (Scottish Executive, 2004).

  1. Asthma control in general practice -- GP and patient perspectives compared.

    Science.gov (United States)

    Henderson, Joan; Hancock, Kerry L; Armour, Carol; Harrison, Christopher; Miller, Graeme

    2013-10-01

    How general practitioners (GPs) and patients perceive asthma control, and concordance between these perceptions, may influence asthma management and medication adherence. The aims of this study were to determine asthma prevalence in adult patients, measure patient asthma control and the correlation between GP and patient perceptions of asthma control or impact. A Supplementary Analysis of Nominated Data (SAND) sub-study of the Bettering the Evaluation and Care of Health (BEACH) program surveyed 2563 patients from 103 GPs. Asthma control was measured using the Asthma Control Questionnaire 5-item version (ACQ-5), and medication adherence by patient self-report. Survey procedures in SAS software and Pearson's correlation statistics were used. Asthma prevalence was 12.7% (95% confidence interval: 10.9-14.5), with good correlation between GP and patient perceptions of asthma control/impact, and with raw ACQ-5 scores. Grouped ACQ-5 scores showed higher levels of uncontrolled asthma. Medication adherence was sub-optimal. The ACQ-5 questions are useful for assessing asthma control, for prompting medication reviews, and for reinforcing benefits of medication compliance to improve long-term asthma control.

  2. General practitioner views on the determinants of test ordering: a theory-based qualitative approach to the development of an intervention to improve immunoglobulin requests in primary care.

    Science.gov (United States)

    Cadogan, S L; McHugh, S M; Bradley, C P; Browne, J P; Cahill, M R

    2016-07-19

    Research suggests that variation in laboratory requesting patterns may indicate unnecessary test use. Requesting patterns for serum immunoglobulins vary significantly between general practitioners (GPs). This study aims to explore GP's views on testing to identify the determinants of behaviour and recommend feasible intervention strategies for improving immunoglobulin test use in primary care. Qualitative semi-structured interviews were conducted with GPs requesting laboratory tests at Cork University Hospital or University Hospital Kerry in the South of Ireland. GPs were identified using a Health Service Executive laboratory list of GPs in the Cork-Kerry region. A random sample of GPs (stratified by GP requesting patterns) was generated from this list. GPs were purposively sampled based on the criteria of location (urban/rural); length of time qualified; and practice size (single-handed/group). Interviews were carried out between December 2014 and February 2015. Interviews were transcribed verbatim using NVivo 10 software and analysed using the framework analysis method. Emerging themes were mapped to the theoretical domains framework (TDF), which outlines 12 domains that can enable or inhibit behaviour change. The behaviour change wheel and behaviour change technique (BCT) taxonomy were then used to identify potential intervention strategies. Sixteen GPs were interviewed (ten males and six females). Findings suggest that intervention strategies should specifically target the key barriers to effective test ordering, while considering the context of primary care practice. Seven domains from the TDF were perceived to influence immunoglobulin test ordering behaviours and were identified as 'mechanisms for change' (knowledge, environmental context and resources, social/professional role and identity, beliefs about capabilities, beliefs about consequences, memory, attention and decision-making processes and behavioural regulation). Using these TDF domains, seven BCTs

  3. Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene

    International Nuclear Information System (INIS)

    Hoatlin, M.E.; Kozak, S.L.; Kabat, D.; Lilly, F.; Chakraborti, A.; Kozak, C.A.

    1990-01-01

    The leukemogenic membrane glycoprotein (gp55) encoded by Friend spleen focus-forming virus appears to bind to erythropoietin receptors (EpoR) to stimulate erythroblastosis. To directly compare the effects of gp55 with erythropoietin (Epo), the authors produced retrovirions that encode either gp55, Epo, or EpoR. After infection with EpoR virus, interleukin 3-dependent DA-3 cells bound 125 I-labeled Epo and grew without interleukin 3 in the presence of Epo. These latter cells, but not parental DA-3 cells, became factor-independent after superinfection either with Epo virus or with Friend spleen focus-forming virus. In addition, Epo virus caused a disease in mice that mimicked Friend erythroleukemia. Although Fv-2 r homozygotes are susceptible to all other retroviral diseases, they are resistant to both Epo viral and Friend viral erythroleukemia. These results indicate that both gp55 and Epo stimulate EpoR and that the Fv-2 gene encodes a protein that controls response to these ligands. However, the Fv-2 protein is not EpoR because the corresponding genes map to opposite ends of mouse chromosome 9. These results have important implications for understanding signal transduction by EpoR and the role of host genetic variation in controlling susceptibility to an oncogenic protein

  4. The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae

    Directory of Open Access Journals (Sweden)

    Lowe Anson W

    2009-07-01

    Full Text Available Abstract Background GP2 is the major membrane protein present in the pancreatic zymogen granule, and is cleaved and released into the pancreatic duct along with exocrine secretions. The function of GP2 is unknown. GP2's amino acid sequence is most similar to that of uromodulin, which is secreted by the kidney. Recent studies have demonstrated uromodulin binding to bacterial Type 1 fimbria. The fimbriae serve as adhesins to host receptors. The present study examines whether GP2 also shares similar binding properties to bacteria with Type 1 fimbria. Commensal and pathogenic bacteria, including E. coli and Salmonella, express type 1 fimbria. Methods An in vitro binding assay was used to assay the binding of recombinant GP2 to defined strains of E. coli that differ in their expression of Type 1 fimbria or its subunit protein, FimH. Studies were also performed to determine whether GP2 binding is dependent on the presence of mannose residues, which is a known determinant for FimH binding. Results GP2 binds E. coli that express Type 1 fimbria. Binding is dependent on GP2 glycosylation, and specifically the presence of mannose residues. Conclusion GP2 binds to Type 1 fimbria, a bacterial adhesin that is commonly expressed by members of the Enterobacteriacae family.

  5. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    Energy Technology Data Exchange (ETDEWEB)

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B. (Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD (USA))

    1991-05-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-(1-14C) glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

  6. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    International Nuclear Information System (INIS)

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B.

    1991-01-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection

  7. Feasibility, acceptability and effectiveness of an online alternative to face-to-face consultation in general practice: a mixed-methods study of webGP in six Devon practices.

    Science.gov (United States)

    Carter, Mary; Fletcher, Emily; Sansom, Anna; Warren, Fiona C; Campbell, John L

    2018-02-15

    To evaluate the feasibility, acceptability and effectiveness of webGP as piloted by six general practices. Mixed-methods evaluation, including data extraction from practice databases, general practitioner (GP) completion of case reports, patient questionnaires and staff interviews. General practices in NHS Northern, Eastern and Western Devon Clinical Commissioning Group's area approximately 6 months after implementing webGP (February-July 2016). Six practices provided consultations data; 20 GPs completed case reports (regarding 61 e-consults); 81 patients completed questionnaires; 5 GPs and 5 administrators were interviewed. Attitudes and experiences of practice staff and patients regarding webGP. WebGP uptake during the evaluation was small, showing no discernible impact on practice workload. The completeness of cross-sectional data on consultation workload varied between practices.GPs judged 41/61 (72%) of webGP requests to require a face-to-face or telephone consultation. Introducing webGP appeared to be associated with shifts in responsibility and workload between practice staff and between practices and patients.81/231 patients completed a postal survey (35.1% response rate). E-Consulters were somewhat younger and more likely to be employed than face-to-face respondents. WebGP appeared broadly acceptable to patients regarding timeliness and quality/experience of care provided. Similar problems were presented by all respondents. Both groups appeared equally familiar with other practice online services; e-consulters were somewhat more likely to have used them.From semistructured staff interviews, it appeared that, while largely acceptable within practice, introducing e-consults had potential for adverse interactions with pre-existing practice systems. There is potential to assess the impact of new systems on consultation patterns by extracting routine data from practice databases. Staff and patients noticed subtle changes to responsibilities associated with

  8. Teaching Form as Form

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    2012-01-01

    understanding of form per se, or, to use an expression from this text, of form as form. This challenge can be reduced to one question: how can design teaching support students in achieving not only the ability to recognize and describe different form-related concepts in existing design (i.e. analytical...

  9. 78 FR 53134 - Proposed Collection; Comment Request

    Science.gov (United States)

    2013-08-28

    ... are properly trained. Requesting and receiving direct feedback from this group would be helpful to...; Comment Request AGENCY: Air Education and Training Command (AETC/A5TS), Department of the Air Force... collection on respondents, including through the use of automated collection techniques or other forms of...

  10. Shuttle requests

    CERN Multimedia

    2007-01-01

    Please note that, to improve the service we provide, a new telephone number - 72500 - has been set up for all shuttle requests concerning: journeys within the CERN site, i.e. official visits or bidders' conferences; journeys to or from the airport or city centre; long-distance journeys. However, it will still be possible to submit requests in writing to Fm.Support@cern. The radio taxi can also still be reached on 76969. The TS/FM group would also like to inform you that details of all light logistics services (transport of persons, distribution and collection of parcels up to 1 tonne, distribution and collection of mail) can be found on the group's website: http://ts-dep.web.cern.ch/ts-dep/groups/fm/fm.htm TS/FM Group 160239

  11. 76 FR 47196 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2011-08-04

    ... OMB Review; Comment Request Title: Request for Assistance for Child Victims of Human Trafficking OMB... through the completion of a Request for Assistance for Child Victims of Human Trafficking form will enable... Human Trafficking Estimated Total Annual Burden Hours: 200. Additional Information: Copies of the...

  12. UK Chemical Nuclear Data Committee request list - 1990

    International Nuclear Information System (INIS)

    Nichols, A.L.

    1990-03-01

    The 1986 UK request list for chemical nuclear data has been reviewed in detail by members of the UK Chemical Nuclear Data Committee. New requirements for data measurements and evaluations have been identified, and specific requests have been withdrawn. A new UK request list has evolved, and is given in the form of tabulations covering measurements and evaluations. (author)

  13. 12 CFR 404.18 - Requests for correction of records.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Requests for correction of records. 404.18 Section 404.18 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Access to Records Under the Privacy Act of 1974 § 404.18 Requests for correction of records. (a) Form. Requests for...

  14. 12 CFR 404.14 - Requirements of request for access.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Requirements of request for access. 404.14 Section 404.14 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Access to Records Under the Privacy Act of 1974 § 404.14 Requirements of request for access. (a) Form. Requests for...

  15. 21 CFR 720.4 - Information requested about cosmetic products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Information requested about cosmetic products. 720... (CONTINUED) COSMETICS VOLUNTARY FILING OF COSMETIC PRODUCT INGREDIENT COMPOSITION STATEMENTS § 720.4 Information requested about cosmetic products. (a) Form FDA-2512 requests information on: (1) The name and...

  16. 76 FR 13273 - Request for Service Corporation Activity

    Science.gov (United States)

    2011-03-10

    ... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Request for Service Corporation Activity AGENCY: Office of Thrift Supervision (OTS), Treasury. ACTION: Notice and request for comment. SUMMARY... collection. Title of Proposal: Request for Service Corporation Activity. OMB Number: 1550-0013. Form Numbers...

  17. Vertical integration - Reducing the load on GP teachers.

    Science.gov (United States)

    Anderson, Katrina; Thomson, Jennifer

    2009-11-01

    With the increased medical student numbers in Australia there is an expectation that general practice will train students, junior doctors and registrars, and the teaching burden for busy general practitioners will rise. We discuss the model of vertical integration of general practice education set up at the Australian National University Medical School in the Australian Capital Territory and southeast New South Wales. This model of vertical integration is unique. It could be adapted in a range of vocational settings and spans medical student, prevocational doctor, registrar and international medical graduate teaching. A key aim of these strategies is to reduce the load on the clinical GP teacher as sustaining their contribution is crucial to the future of training in general practice.

  18. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  19. Work-family balance by women GP specialist trainees in Slovenia: a qualitative study.

    Science.gov (United States)

    Petek, Davorina; Gajsek, Tadeja; Petek Ster, Marija

    2016-01-28

    Women physicians face many challenges while balancing their many roles: doctor, specialist trainee, mother and partner. The most opportune biological time for a woman to start a family coincides with a great deal of demands and requirements at work. In this study we explored the options and capabilities of women GP specialist trainees in coordinating their family and career. This is a phenomenological qualitative research. Ten GP specialist trainees from urban and rural areas were chosen by the purposive sampling technique, and semi-structured in-depth interviews were conducted, recorded, transcribed and analysed by using thematic analysis process. Open coding and the book of codes were formed. Finally, we performed the process of code reduction by identifying the themes, which were compared, interpreted and organised in the highest analytical units--categories. One hundred fifty-five codes were identified in the analysis, which were grouped together into eleven themes. The identified themes are: types, causes and consequences of burdens, work as pleasure and positive attitude toward self, priorities, planning and help, and understanding of superiors, disburdening and changing in specialisation. The themes were grouped into four large categories: burdens, empowerment, coordination and needs for improvement. Women specialist trainees encounter intense burdens at work and home due to numerous demands and requirements during their specialisation training. In addition, there is also the issue of the work-family conflict. There are many consequences regarding burden and strain; however, burnout stands out the most. In contrast, reconciliation of work and family life and needs can be successful. The key element is empowerment of women doctors. The foremost necessary systemic solution is the reinforcement of general practitioners in primary health care and their understanding of the specialisation training scheme with more flexible possibilities for time adaptations of

  20. Individual factors and GP approach as predictors for the outcome of rehabilitation among long-term sick listed cases

    DEFF Research Database (Denmark)

    Rasmussen, K.; Andersen, JH

    2005-01-01

    care professionals were found important for a positive outcome of the programme. Especially stable relations to a single General Practitioner (GP), who took good care of the patient in the form of giving good information about health and social possibilities, and an empathic attitude toward these hard...... than 1 year. The remainder had been transferred to receiving social benefits after having exceeded the time limit for being sick-listed. A plan of action for active rehabilitation, which was made at the end of the 8-week rehabilitation programme, was only poorly fulfilled after 9 months, 48% were still...

  1. Adaptive Municipal e-forms

    NARCIS (Netherlands)

    Kuiper, P.M.; van Dijk, Elisabeth M.A.G.; Boerma, A.K.; Weibelzahl, S.; Cristea, A.

    2006-01-01

    Adaptation of electronic forms seems to be a step forward to reduce the burden for people who fill in forms. Municipalities more and more offer eforms online that can be used to request a municipal product or service. To create adaptive e-forms that satisfy the need of end-users, involvement of

  2. 78 FR 25091 - Submission for OMB Review; 30-Day Comment Request: Request for Human Embryonic Stem Cell Line To...

    Science.gov (United States)

    2013-04-29

    ...; 30-Day Comment Request: Request for Human Embryonic Stem Cell Line To Be Approved for Use in NIH... Embryonic Stem Cell Line to be Approved for Use in NIH-Funded Research, 0925-0601, Expiration Date 04/30... Information Collection: The form is used by applicants to request that human embryonic stem cell lines be...

  3. 78 FR 13688 - Proposed Collection; 60-Day Comment Request: Request for Human Embryonic Stem Cell Line To Be...

    Science.gov (United States)

    2013-02-28

    ... Comment Request: Request for Human Embryonic Stem Cell Line To Be Approved for Use in NIH Funded Research... Embryonic Stem Cell Line to be Approved for Use in NIH Funded Research. OMB No. 0925-0601-- Expiration Date... and Use of Information Collection: The form is used by applicants to request that human embryonic stem...

  4. 48 CFR 13.307 - Forms.

    Science.gov (United States)

    2010-10-01

    ...) Other than commercial items. (1) Except when quotations are solicited electronically or orally, the SF 1449; SF 18, Request for Quotations; or an agency form/automated format may be used. Each agency request for quotations form/automated format should conform with the SF 18 or SF 1449 to the maximum...

  5. Binding kinetics of aptamers to gp120 derived from HIV-1 subtype C

    CSIR Research Space (South Africa)

    Millroy, L

    2011-02-01

    Full Text Available aptamers with specific and strong affinity to the HIV-1 envelope glycoprotein gp120 and act as novel HIV-1 entry inhibitor drugs or as targeted drug delivery systems to HIV-1 infected cells. Prior to any downstream applications, novel gp120 aptamers need...

  6. Admission and poor performance of trainees in the postgraduate GP training in the Netherlands

    NARCIS (Netherlands)

    Vermeulen, M.I.

    2014-01-01

    Until 2014 the selection for the Dutch postgraduate GP training was conducted locally, on the eight GP departments. The procedure consisted of a letter of application and a semi-structured interview. We investigated to what extend department of choice, candidates’ characteristics and qualities

  7. A functional F analogue of AcMNPV GP64 is from the Agrotis segetum granulovirus

    NARCIS (Netherlands)

    Yin, F.; Wang, M.; Tan, Y.; Deng, F.; Vlak, J.M.; Hu, Z.H.; Wang, H.

    2008-01-01

    The envelope fusion protein F of Plutella xylostella granulovirus is a computational analogue of the GP64 envelope fusion protein of Autographa californica nucleopolyhedrovirus (AcMNPV). Granulovirus (GV) F proteins were thought to be unable to functionally replace GP64 in the AcMNPV pseudotyping

  8. Selected Thermophysical Properties of 2,2 Dimethylcyclopentyl Methylphosphonofluoridate (GP) and 2,2 Dimethylcyclopentanol (DMCP)

    Science.gov (United States)

    2016-09-01

    chromatography using a thermal conductivity detector (GC-TCD). Table 1. Sample Information for GP and DMCP Chemical Name Mole Fraction Purity...Proving Ground, MD, 1983; UNCLASSIFIED Report (ADC033491). 23. Weast, R.C. CRC Handbook of Chemistry and Physics, 53rd ed.; CRC Press: Boca Raton, FL...gas chromatography GD pinacolyl methylphosphonofluoridate GF cyclohexyl methylphosphonofluoridate GP 2,2-dimethylcyclopentyl

  9. Triage of febrile children at a GP cooperative : determinants of a consultation

    NARCIS (Netherlands)

    Monteny, Miriam; Berger, Marjolein Y.; van der Wouden, Johannes C.; Broekman, Berth J.; Koes, Bart W.

    Background Most febrile children contacting a GP cooperative are seen by a GP, although the incidence of serious illness is low. The guidelines for triage might not be suitable in primary care. Aim To investigate the determinants related to the outcome of triage in febrile children. Design of study

  10. Screening and Identification of ssDNA Aptamer for Human GP73

    Directory of Open Access Journals (Sweden)

    Jingchun Du

    2015-01-01

    Full Text Available As one tumor marker of HCC, Golgi Protein 73 (GP73 is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens.

  11. The effect of gender medicine education in GP training: a prospective cohort study.

    Science.gov (United States)

    Dielissen, Patrick; Verdonk, Petra; Waard, Magreet Wieringa-de; Bottema, Ben; Lagro-Janssen, Toine

    2014-11-01

    The purpose of this study is to compare the change in general practitioner (GP) trainees' gender awareness following a modular gender medicine programme or a mainstream gender medicine programme. In 2007, a prospective study was conducted in three cohorts of in total 207 GP trainees who entered GP training in the Netherlands. The outcome measure was the Nijmegen Gender Awareness in Medicine Scale and a 16-item gender knowledge questionnaire. Two gender medicine teaching methods were compared: a modular approach (n = 75) versus a mainstream approach (n = 72). Both strategies were compared with a control cohort (n = 60). Statistical analysis included analysis of variance and t-tests. The overall response rates for the modular, mainstream and control cohort were 78, 72 and 82 %, respectively. There was a significant difference in change in gender knowledge scores between the modular cohort compared with the mainstream and control cohort (p = 0.049). There were no statistical differences between the cohorts on gender sensitivity and gender role ideology. At entry and end, female GP trainees demonstrated significantly higher gender awareness than male GP trainees. A modular teaching method is not a more favourable educational method to teach gender medicine in GP training. Female GP trainees are more gender aware, but male GP trainees are not unaware of gender-related issues.

  12. The belonging of gpMuc, a glycoprotein from Mucuna pruriens seeds, to the Kunitz-type trypsin inhibitor family explains its direct anti-snake venom activity.

    Science.gov (United States)

    Scirè, Andrea; Tanfani, Fabio; Bertoli, Enrico; Furlani, Emiliano; Nadozie, Hope-Onyekwere N; Cerutti, Helena; Cortelazzo, Alessio; Bini, Luca; Guerranti, Roberto

    2011-07-15

    In Nigeria, Mucuna pruriens seeds are locally prescribed as an oral prophylactic for snake bite and it is claimed that when two seeds are swallowed they protect the individual for a year against snake bites. In order to understand the Mucuna pruriens antisnake properties, the proteins from the acqueous extract of seeds were purified by three chromatographic steps: ConA affinity chromatography, tandem anionic-cationic exchange and gel filtration, obtaining a fraction conventionally called gpMucB. This purified fraction was analysed by SDS-PAGE obtaining 3 bands with apparent masses ranging from 20 to 24 kDa, and by MALDI-TOF which showed two main peaks of 21 and 23 kDa and another small peak of 19 kDa. On the other hand, gel filtration analysis of the native protein indicated a molecular mass of about 70 kDa suggesting that in its native form, gpMucB is most likely an oligomeric multiform protein. Infrared spectroscopy of gpMucB indicated that the protein is particularly thermostable both at neutral and acidic pHs and that it is an all beta protein. All data suggest that gpMucB belongs to the Kunitz-type trypsin inhibitor family explaining the direct anti-snake venom activity of Mucuna pruriens seeds. Copyright © 2011 Elsevier GmbH. All rights reserved.

  13. Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

    Directory of Open Access Journals (Sweden)

    Johansson Ingegerd

    2007-06-01

    Full Text Available Abstract Background Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of Streptococcus mutans (implicated in caries, harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of S. mutans. Methods A case-referent study was performed in 12-year-old Swedish children with high (n = 19 or low (n = 19 caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of S. mutans using the partial least squares (PLS multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms. Results All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively. The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37 and saliva adhesion of S. mutans Ingbritt (VIP = 1.47. The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of S. mutans strains Ingbritt and NG8 and Lactococcus lactis expressing AgI/II adhesins (SpaP or PAc compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins. Conclusion Gp-340 I behaves as a caries

  14. Comprehensive functional analysis of N-linked glycans on Ebola virus GP1.

    Science.gov (United States)

    Lennemann, Nicholas J; Rhein, Bethany A; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy

    2014-01-28

    Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. Filovirus outbreaks occur sporadically throughout central Africa, causing high fatality rates among the general public and health care workers. These unpredictable hemorrhagic fever outbreaks are caused by multiple species of Ebola viruses, as well as Marburg virus. While filovirus

  15. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

    2017-01-11

    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

  16. Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

    Science.gov (United States)

    Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

    2012-01-01

    Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

  17. 77 FR 9259 - Agency Information Collection Activities: Forms G-1041 and G-1041A, Extension of a Currently...

    Science.gov (United States)

    2012-02-16

    ..., Genealogy Index Search Request and Genealogy Records Request. The Department of Homeland Security, U.S... the Forms/Collections: Genealogy Index Search Request and Genealogy Records Request. (3) Agency form.... USCIS will use these forms will to facilitate an accurate and timely response to genealogy index search...

  18. The Influences of Glycosylation on the Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines

    National Research Council Canada - National Science Library

    Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L; Garrison, Aura R; Smith, Jeffrey M; Paragas, Jason; Hogan, Robert J; Schmaljohn, Connie

    2006-01-01

    ... or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP...

  19. 77 FR 10558 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Request for...

    Science.gov (United States)

    2012-02-22

    ... Collection; Comments Requested: Request for Recognition of a Non-Profit Religious, Charitable, Social Service... Recognition of a Non- profit Religious, Charitable, Social Service, or Similar Organization. (3) Agency form... requirements for recognition by the Board as a legal service provider, which then would allow its designated...

  20. A gp41-based heteroduplex mobility assay provides rapid and accurate assessment of intrasubtype epidemiological linkage in HIV type 1 heterosexual transmission Pairs.

    Science.gov (United States)

    Manigart, Olivier; Boeras, Debrah I; Karita, Etienne; Hawkins, Paulina A; Vwalika, Cheswa; Makombe, Nathan; Mulenga, Joseph; Derdeyn, Cynthia A; Allen, Susan; Hunter, Eric

    2012-12-01

    A critical step in HIV-1 transmission studies is the rapid and accurate identification of epidemiologically linked transmission pairs. To date, this has been accomplished by comparison of polymerase chain reaction (PCR)-amplified nucleotide sequences from potential transmission pairs, which can be cost-prohibitive for use in resource-limited settings. Here we describe a rapid, cost-effective approach to determine transmission linkage based on the heteroduplex mobility assay (HMA), and validate this approach by comparison to nucleotide sequencing. A total of 102 HIV-1-infected Zambian and Rwandan couples, with known linkage, were analyzed by gp41-HMA. A 400-base pair fragment within the envelope gp41 region of the HIV proviral genome was PCR amplified and HMA was applied to both partners' amplicons separately (autologous) and as a mixture (heterologous). If the diversity between gp41 sequences was low (<5%), a homoduplex was observed upon gel electrophoresis and the transmission was characterized as having occurred between partners (linked). If a new heteroduplex formed, within the heterologous migration, the transmission was determined to be unlinked. Initial blind validation of gp-41 HMA demonstrated 90% concordance between HMA and sequencing with 100% concordance in the case of linked transmissions. Following validation, 25 newly infected partners in Kigali and 12 in Lusaka were evaluated prospectively using both HMA and nucleotide sequences. Concordant results were obtained in all but one case (97.3%). The gp41-HMA technique is a reliable and feasible tool to detect linked transmissions in the field. All identified unlinked results should be confirmed by sequence analyses.

  1. Binding of HIV-1 gp120 to DC-SIGN promotes ASK-1-dependent activation-induced apoptosis of human dendritic cells.

    Directory of Open Access Journals (Sweden)

    Yongxiong Chen

    2013-01-01

    Full Text Available During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC, including DC-SIGN⁺ cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN⁺ blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV⁺ serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN⁺ DC that were isolated directly from HIV-1⁺ individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential

  2. Classification as clustering: a Pareto cooperative-competitive GP approach.

    Science.gov (United States)

    McIntyre, Andrew R; Heywood, Malcolm I

    2011-01-01

    Intuitively population based algorithms such as genetic programming provide a natural environment for supporting solutions that learn to decompose the overall task between multiple individuals, or a team. This work presents a framework for evolving teams without recourse to prespecifying the number of cooperating individuals. To do so, each individual evolves a mapping to a distribution of outcomes that, following clustering, establishes the parameterization of a (Gaussian) local membership function. This gives individuals the opportunity to represent subsets of tasks, where the overall task is that of classification under the supervised learning domain. Thus, rather than each team member representing an entire class, individuals are free to identify unique subsets of the overall classification task. The framework is supported by techniques from evolutionary multiobjective optimization (EMO) and Pareto competitive coevolution. EMO establishes the basis for encouraging individuals to provide accurate yet nonoverlaping behaviors; whereas competitive coevolution provides the mechanism for scaling to potentially large unbalanced datasets. Benchmarking is performed against recent examples of nonlinear SVM classifiers over 12 UCI datasets with between 150 and 200,000 training instances. Solutions from the proposed coevolutionary multiobjective GP framework appear to provide a good balance between classification performance and model complexity, especially as the dataset instance count increases.

  3. Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review.

    Science.gov (United States)

    Le Floch, B; Bastiaens, H; Le Reste, J Y; Lingner, H; Hoffman, R D; Czachowski, S; Assenova, R; Koskela, T H; Klemenc-Ketis, Z; Nabbe, P; Sowinska, A; Montier, T; Peremans, L

    2016-09-13

    Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.

  4. Esters of the Marine-Derived Triterpene Sipholenol A Reverse P-GP-Mediated Drug Resistance

    Directory of Open Access Journals (Sweden)

    Yongchao Zhang

    2015-04-01

    Full Text Available Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1. Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines, we identified that the semisynthetic esters sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from [3H]-paclitaxel accumulation and efflux studies suggested that these two triterpenoids were able to increase the intracellular accumulation of paclitaxel by inhibiting its active efflux. In addition, western blot analysis revealed that these two compounds did not alter the expression levels of P-gp when treated up to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp membranes, which suggested that they might be substrates of P-gp. Moreover, in silico molecular docking studies revealed the virtual binding modes of these two compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may represent potential reversal agents for the treatment of multidrug resistant cancers.

  5. Characterization of Human Colorectal Cancer MDR1/P-gp Fab Antibody

    Directory of Open Access Journals (Sweden)

    Xuemei Zhang

    2013-01-01

    Full Text Available In this study, the peptide sized 21 kDa covering P-gp transmembrane region was first prepared for generating a novel mouse monoclonal antibody Fab fragment with biological activity against multiple drug resistance protein P-gp21 by phage display technology. Phage-displayed antibody library prepared from mice spleen tissues was selected against the recombinant protein P-gp21 with five rounds of panning. A number of clones expressing Fab bound to P-gp21, showing neutralized activity in vitro, were isolated and screened by enzyme-linked immunosorbent assay based on its recognition properties to P-gp21 and human colorectal cancer tissue homogenate, resulting in identification of an optimal recombinant Fab clone (Number 29. Further characterization by recloning number 29 into an expression vector showed significant induction of the Fab antibody in the clone number 29 by Isopropyl β-D-1-thiogalactopyranoside (IPTG. After purified by HiTrap Protein L, the specificity of the Fab antibody to P-gp21 was also confirmed. Not only was the targeted region of this monoclonal Fab antibody identified as a 16-peptide epitope (ALKDKKELEGSGKIAT comprising residues 883–898 within the transmembrane (TM domain of human P-gp, but also the binding ability with it was verified. The clinical implication of our results for development of personalized therapy of colorectal cancer will be further studied.

  6. Are there practical opportunities for developing leadership skills during GP training and beyond? A survey of GP trainees and trainers in South East Scotland.

    Science.gov (United States)

    Curry, Nicola; Denney, MeiLing

    2016-01-01

    There is currently a lack of formal training in leadership skills, particularly during GP training. This study aimed to explore the current training and practical opportunities which exist, specifically exploring the views of GP trainees and trainers. An electronic questionnaire was sent to 266 GP trainees and trainers in south-east Scotland. Questions focused on respondents' experience of leadership-specific training and opportunities to engage with leadership roles. There were a total of 76 respondents (28.6% response rate). Response rate was 19.0% in trainees and 34.6% in trainers. A majority of respondents (80.0%) were established GPs. Of those who had received training in leadership, most (72.1%) underwent this after qualifying as a GP. Respondents identified a range of leadership roles within and outside the practice covering clinical and non-clinical areas. Most were interested in future leadership roles (46.7% moderately interested; 28% very interested). More time, training opportunities and the presence of GP role models were motivating factors in terms of participants' readiness to take on future leadership roles. Signposting trainees, trainers and general practitioners to leadership opportunities and training would be relatively easy but addressing a lack of motivating factors at a local level is essential. The effectiveness of such training and opportunities for experiential learning in leadership roles requires further research.

  7. The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

    Science.gov (United States)

    Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

    2016-01-01

    HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

  8. ROME (Request Object Management Environment)

    Science.gov (United States)

    Kong, M.; Good, J. C.; Berriman, G. B.

    2005-12-01

    Most current astronomical archive services are based on an HTML/ CGI architecture where users submit HTML forms via a browser and CGI programs operating under a web server process the requests. Most services return an HTML result page with URL links to the result files or, for longer jobs, return a message indicating that email will be sent when the job is done. This paradigm has a few serious shortcomings. First, it is all too common for something to go wrong and for the user to never hear about the job again. Second, for long and complicated jobs there is often important intermediate information that would allow the user to adjust the processing. Finally, unless some sort of custom queueing mechanism is used, background jobs are started immediately upon receiving the CGI request. When there are many such requests the server machine can easily be overloaded and either slow to a crawl or crash. Request Object Management Environment (ROME) is a collection of middleware components being developed under the National Virtual Observatory Project to provide mechanism for managing long jobs such as computationally intensive statistical analysis requests or the generation of large scale mosaic images. Written as EJB objects within the open-source JBoss applications server, ROME receives processing requests via a servelet interface, stores them in a DBMS using JDBC, distributes the processing (via queuing mechanisms) across multiple machines and environments (including Grid resources), manages realtime messages from the processing modules, and ensures proper user notification. The request processing modules are identical in structure to standard CGI-programs -- though they can optionally implement status messaging -- and can be written in any language. ROME will persist these jobs across failures of processing modules, network outages, and even downtime of ROME and the DBMS, restarting them as necessary.

  9. Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

    Directory of Open Access Journals (Sweden)

    Xinghui Li

    Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

  10. PRAGMATIC TRANSFER IN REQUEST REALIZATIONS

    Directory of Open Access Journals (Sweden)

    Indawan Syahri

    2007-01-01

    Full Text Available This study investigates the pragmatic transfer in English request realizations made by EFL learners, i.e. the proficient learners. The subjects were students of an English Study Program who obtained TOEFL-like scores of at least 450. The data were collected by means of DCT-questionnaires and Role-plays. The results show that the subjects realize requests in the form of external modifications more frequently. Most of them embed their requests with supportive moves dominantly. They enfold the acts with the moves before, after or in both positions. Of the three positions, they mostly insert the moves initial position, i.e., through inductive patterns. This is due to pragmatic transfer.

  11. Membrane insertion and assembly of epitope-tagged gp9 at the tip of the M13 phage

    Directory of Open Access Journals (Sweden)

    Kuhn Andreas

    2011-09-01

    Full Text Available Abstract Background Filamentous M13 phage extrude from infected Escherichia coli with a tip structure composed of gp7 and gp9. This tip structure is extended by the assembly of the filament composed of the major coat protein gp8. Finally, gp3 and gp6 terminate the phage structure at the proximal end. Up to now, gp3 has been the primary tool for phage display technology. However, gp7, gp8 and gp9 could also be used for phage display and these phage particles should bind to two different or more surfaces when the modified coat proteins are combined. Therefore, we tested here if the amino-terminal end of gp9 can be modified and whether the modified portion is exposed and detectable on the M13 phage particles. Results The amino-terminal region of gp9 was modified by inserting short sequences that encode antigenic epitopes. We show here that the modified gp9 proteins correctly integrate into the membrane using the membrane insertase YidC exposing the modified epitope into the periplasm. The proteins are then efficiently assembled onto the phage particles. Also extensions up to 36 amino acid residues at the amino-terminal end of gp9 did not interfere with membrane integration and phage assembly. The exposure of the antigenic tags on the phage was visualised with immunogold labelling by electron microscopy and verified by dot blotting with antibodies to the tags. Conclusions Our results suggest that gp9 at the phage tip is suitable for the phage display technology. The modified gp9 can be supplied in trans from a plasmid and fully complements M13 phage with an amber mutation in gene 9. The modified phage tip is very well accessible to antibodies.

  12. Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms.

    Science.gov (United States)

    Watkins, N A; O'Connor, M N; Rankin, A; Jennings, N; Wilson, E; Harmer, I J; Davies, L; Smethurst, P A; Dudbridge, F; Farndale, R W; Ouwehand, W H

    2006-06-01

    Common genetic variants of cell surface receptors contribute to differences in functional responses and disease susceptibility. We have previously shown that single nucleotide polymorphisms (SNPs) in platelet glycoprotein VI (GP6) determine the extent of response to agonist. In addition, SNPs in the GP6 gene have been proposed as risk factors for coronary artery disease. To completely characterize genetic variation in the GP6 gene we generated a high-resolution SNP map by sequencing the promoter, exons and consensus splice sequences in 94 non-related Caucasoids. In addition, we sequenced DNA encoding the ligand-binding domains of GP6 from non-human primates to determine the level of evolutionary conservation. Eighteen SNPs were identified, six of which encoded amino acid substitutions in the mature form of the protein. The single non-synonymous SNP identified in the exons encoding the ligand-binding domains, encoding for a 103Leu > Val substitution, resulted in reduced ligand binding. Two common protein isoforms were confirmed in Caucasoid with frequencies of 0.82 and 0.15. Variation at the GP6 locus was characterized further by determining SNP frequency in over 2000 individuals from different ethnic backgrounds. The SNPs were polymorphic in all populations studied although significant differences in allele frequencies were observed. Twelve additional GP6 protein isoforms were identified from the genotyping results and, despite extensive variation in GP6, the sequence of the ligand-binding domains is conserved. Sequences from non-human primates confirmed this observation. These data provide valuable information for the optimal selection of genetic variants for use in future association studies.

  13. The C-terminal tail of the gp41 transmembrane envelope glycoprotein of HIV-1 clades A, B, C, and D may exist in two conformations: an analysis of sequence, structure, and function

    International Nuclear Information System (INIS)

    Hollier, Mark J.; Dimmock, Nigel J.

    2005-01-01

    In addition to the major ectodomain, the gp41 transmembrane glycoprotein of HIV-1 is now known to have a minor ectodomain that is part of the long C-terminal tail. Both ectodomains are highly antigenic, carry neutralizing and non-neutralizing epitopes, and are involved in virus-mediated fusion activity. However, data have so far been biologically based, and derived solely from T cell line-adapted (TCLA), B clade viruses. Here we have carried out sequence and theoretically based structural analyses of 357 gp41 C-terminal sequences of mainly primary isolates of HIV-1 clades A, B, C, and D. Data show that all these viruses have the potential to form a tail loop structure (the minor ectodomain) supported by three, β-sheet, membrane-spanning domains (MSDs). This means that the first (N-terminal) tyrosine-based sorting signal of the gp41 tail is situated outside the cell membrane and is non-functional, and that gp41 that reaches the cell surface may be recycled back into the cytoplasm through the activity of the second tyrosine-sorting signal. However, we suggest that only a minority of cell-associated gp41 molecules - those destined for incorporation into virions - has 3 MSDs and the minor ectodomain. Most intracellular gp41 has the conventional single MSD, no minor ectodomain, a functional first tyrosine-based sorting signal, and in line with current thinking is degraded intracellularly. The gp41 structural diversity suggested here can be viewed as an evolutionary strategy to minimize HIV-1 envelope glycoprotein expression on the cell surface, and hence possible cytotoxicity and immune attack on the infected cell

  14. The impact of leadership development on GP mental health commissioning.

    Science.gov (United States)

    Dickerson, Emma; Fenge, Lee-Ann; Rosenorn-Lanng, Emily

    2017-07-03

    Purpose This paper aims to explore the learning needs of general practitioners (GPs) involved in commissioning mental health provision in England, and offer an evaluation of a leadership and commissioning skills development programme for Mental Health Commissioners. Design/methodology/approach Retrospective mixed method, including online mixed method survey, rating participants' knowledge, skills, abilities, semi-structured telephone interviews and third-party questionnaires were used. Results were analysed for significant differences using the Wilcoxon Signed Ranks test. Open-ended responses and interview transcripts were analysed thematically. Findings Indicative results showed that participants perceived significant impacts in ability across eight key question groups evaluated. Differences were found between the perceived and observed impact in relation to technical areas covered within the programme which were perceived as the highest scoring impacts by participants. Research limitations/implications The indicative results show a positive impact on practice has been both perceived and observed. Findings illustrate the value of this development programme on both the personal development of GP Mental Health Commissioners and commissioning practice. Although the findings of this evaluation increase understanding in relation to an important and topical area, larger scale, prospective evaluations are required. Impact evaluations could be embedded within future programmes to encourage higher participant and third-party engagement. Future evaluations would benefit from collection and analysis of attendance data. Further research could involve patient, service user and carer perspectives on mental health commissioning. Originality value Results of this evaluation could inform the development of future learning programmes for mental health commissioners as part of a national approach to improve mental health provision.

  15. The Astringency of the GP Algorithm for Forecasting Software Failure Data Series

    Directory of Open Access Journals (Sweden)

    Yong-qiang Zhang

    2007-05-01

    Full Text Available The forecasting of software failure data series by Genetic Programming (GP can be realized without any assumptions before modeling. This discovery has transformed traditional statistical modeling methods as well as improved consistency for model applicability. The individuals' different characteristics during the evolution of generations, which are randomly changeable, are treated as Markov random processes. This paper also proposes that a GP algorithm with "optimal individuals reserved strategy" is the best solution to this problem, and therefore the adaptive individuals finally will be evolved. This will allow practical applications in software reliability modeling analysis and forecasting for failure behaviors. Moreover it can verify the feasibility and availability of the GP algorithm, which is applied to software failure data series forecasting on a theoretical basis. The results show that the GP algorithm is the best solution for software failure behaviors in a variety of disciplines.

  16. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Directory of Open Access Journals (Sweden)

    Ling-ling Shen

    2015-01-01

    Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  17. A combined AHP-GP model to allocate internal auditing time to ...

    African Journals Online (AJOL)

    Analytic hierarchy process, goal programming, internal audit, risk assessment. ..... Services area and are listed, together with their associated management ..... [2] Badri MA, 2001, A combined AHP-GP model for quality control systems, Interna-.

  18. 76 FR 43331 - Labor-Management Relations Information Collection Requests

    Science.gov (United States)

    2011-07-20

    ... FEDERAL MEDIATION AND CONCILIATION SERVICE Labor-Management Relations Information Collection... the following public information collection requests (ICR) to the Office of Management and Budget (OMB... information collection requests are FMCS forms: Arbitrator's Report and Fee Statement (Agency Form R-19...

  19. 78 FR 52168 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2013-08-22

    ... Review; Comment Request ACTION: Notice. The Department of Defense has submitted to OMB for clearance, the.... Title, Associated Form and OMB Number: Request for Armed Forces Participation in Public Events; DD Form... evaluate the eligibility of events to receive Armed Forces community relations support and to determine...

  20. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    International Nuclear Information System (INIS)

    Costantini, Lindsey M.; Irvin, Susan C.; Kennedy, Steven C.; Guo, Feng; Goldstein, Harris; Herold, Betsy C.; Snapp, Erik L.

    2015-01-01

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells

  1. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    Energy Technology Data Exchange (ETDEWEB)

    Costantini, Lindsey M. [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Irvin, Susan C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Kennedy, Steven C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Guo, Feng [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Goldstein, Harris; Herold, Betsy C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Snapp, Erik L., E-mail: erik-lee.snapp@einstein.yu.edu [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

    2015-02-15

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

  2. Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

    International Nuclear Information System (INIS)

    Bellamy-McIntyre, Anna K.; Baer, Severine; Ludlow, Louise; Drummer, Heidi E.; Poumbourios, Pantelis

    2010-01-01

    The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1 QH1549.13 blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.

  3. Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

    Science.gov (United States)

    Kesby, James P.; Markou, Athina; Semenova, Svetlana

    2014-01-01

    Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

  4. Using photography to enhance GP trainees’ reflective practice and professional development.

    OpenAIRE

    Rutherford,; Forde, Emer; Priego-Hernández, J.; Butcher, Aurelia; Wedderburn, Clare

    2018-01-01

    The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most GP training programmes. Teaching through the Humanities is a growing area within medical education, but one which is often considered a voluntary ‘add on’ for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees’ reflective capacity, self awareness and professional developm...

  5. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  6. Crystal structure of the RNase T1 Gp c U complex

    International Nuclear Information System (INIS)

    Arni, R.K.

    1996-01-01

    Full text. Ribonuclease T 1 (RNase T 1 ; EC 3.1.27.3) a member of an extensive gene family of orthologous enzymes from fungi and bacteria that display sequence and structural homology. RNase T 1 is a guanine specific extracellular enzyme from Aspergillus oryzae that cleaves single stranded RNA by catalytic transesterification of 3,5 diester links to 2,3 cyclic diesters at guanylyl residues followed by their catalytic hydrolysis to corresponding 3 monoester. It has been suggested that subsites at both the 5 and 3 sides of a cleavable guanylyl residue in RNA substrates exist. The structure of the monomeric RNase T 1 2 guanosine mono phosphate was determined at 1.9 A resolution using syncrotron radiation (Arni et al. 1987) and revealed the specific interactions at the base recognition and catalytic sites (Arni et al., 1988). The structure of native RNase T 1 indicated the conformational changes of the amino acids forming the base recognition site (Arni et al., 1992). This protein has now been crystallized with Gpc U (Guanylyl (3,6) 6 deoxyhomouridine) which is an isosteric phosphonate analogue of the RNA fragment GpU (Guanylyl (3,5) Uridine), with the 5 oxygen of the uridine moiety replaced by a methylene. The structure has been determined and refined at 2.0 A resolution and indicates the existence of subsites and a novel ribose interaction. (author)

  7. Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Sanders, Rogier W.; Johan Klasse, Per; Moore, John P.

    2012-01-01

    A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.

  8. Intrinsic acid-base properties of a hexa-2'-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT): neighboring effects and isomeric equilibria.

    Science.gov (United States)

    Domínguez-Martín, Alicia; Johannsen, Silke; Sigel, Astrid; Operschall, Bert P; Song, Bin; Sigel, Helmut; Okruszek, Andrzej; González-Pérez, Josefa María; Niclós-Gutiérrez, Juan; Sigel, Roland K O

    2013-06-17

    The intrinsic acid-base properties of the hexa-2'-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT) [=(A1∙G2∙G3∙C4∙C5∙T6)=(HNPP)⁵⁻] have been determined by ¹H NMR shift experiments. The pKa values of the individual sites of the adenosine (A), guanosine (G), cytidine (C), and thymidine (T) residues were measured in water under single-strand conditions (i.e., 10% D₂O, 47 °C, I=0.1 M, NaClO₄). These results quantify the release of H⁺ from the two (N7)H⁺ (G∙G), the two (N3)H⁺ (C∙C), and the (N1)H⁺ (A) units, as well as from the two (N1)H (G∙G) and the (N3)H (T) sites. Based on measurements with 2'-deoxynucleosides at 25 °C and 47 °C, they were transferred to pKa values valid in water at 25 °C and I=0.1 M. Intramolecular stacks between the nucleobases A1 and G2 as well as most likely also between G2 and G3 are formed. For HNPP three pKa clusters occur, that is those encompassing the pKa values of 2.44, 2.97, and 3.71 of G2(N7)H⁺, G3(N7)H⁺, and A1(N1)H⁺, respectively, with overlapping buffer regions. The tautomer populations were estimated, giving for the release of a single proton from five-fold protonated H₅(HNPP)(±) , the tautomers (G2)N7, (G3)N7, and (A1)N1 with formation degrees of about 74, 22, and 4%, respectively. Tautomer distributions reveal pathways for proton-donating as well as for proton-accepting reactions both being expected to be fast and to occur practically at no "cost". The eight pKa values for H₅(HNPP)(±) are compared with data for nucleosides and nucleotides, revealing that the nucleoside residues are in part affected very differently by their neighbors. In addition, the intrinsic acidity constants for the RNA derivative r(A1∙G2∙G3∙C4∙C5∙U6), where U=uridine, were calculated. Finally, the effect of metal ions on the pKa values of nucleobase sites is briefly discussed because in this way deprotonation reactions can easily be shifted to the physiological pH range. Copyright © 2013 WILEY

  9. 78 FR 34175 - Proposed Information Collection (Request for Employment Information in Connection With Claim for...

    Science.gov (United States)

    2013-06-06

    ... techniques or the use of other forms of information technology. Title: Request for Employment Information in... (Request for Employment Information in Connection With Claim for Disability Benefits) Activity: Comment...: Extension of a currently approved collection. Abstract: VA Form 21-4192 is used to request employment...

  10. HIV-1 gp120 and drugs of abuse: interactions in the central nervous system.

    Science.gov (United States)

    Silverstein, Peter S; Shah, Ankit; Weemhoff, James; Kumar, Santosh; Singh, D P; Kumar, Anil

    2012-07-01

    HIV-1 infection is a global public health problem with more than 34 million people living with HIV infection. Although great strides have been made in treating this epidemic with therapeutic agents, the increase in patient life span has been coincident with an increase in the prevalence of HIV-associated neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic effects of viral proteins that are shed from HIV-infected microglial cells. One of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in neurons, as well as numerous indirect effects such as an increase in inflammatory cytokines, an increase in oxidative stress, and an increase in permeability of the blood-brain barrier. In many patients, the use of drugs of abuse (DOA) exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and morphine are three DOAs that are commonly used by those infected with HIV-1. All three of these DOAs have been demonstrated to increase oxidative stress in the CNS as well as to increase permeability of the blood-brain barrier. Numerous model systems have demonstrated that these DOAs have the capability of exacerbating the neurotoxic effects of gp120. This review will summarize the neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine and morphine on the CNS, and the combined effects of gp120 in the context of these drugs.

  11. The characteristics of general practice and the attractiveness of working as a GP: medical students' views.

    Science.gov (United States)

    Landstrom, Bjorn; Mattsson, Bengt; Nordin, Per; Rudebeck, Carl E

    2014-03-15

    The aim of the study was to investigate medical students' views on general practice based on their experiences in training, and to find out whether there were certain views associated with the intention to become a GP. A questionnaire, based on our earlier studies about GP working behaviour, was handed out to medical students in terms 1, 3, 5, 7, 10 and 11 of undergraduate studies in Gothenburg, Sweden. The analysis comprised statistical descriptions and comparisons. The students regarded general practice positively. They found the work environment good, the GP's awareness of patients' living conditions necessary, and that GP work requires medical breadth. The status of the GP in the medical profession was not considered high. One-fourth of the students strongly agreed with the possibility of a future as a GP. This attitude was statistically associated with support to the statements that general practice offers a good work environment and should be a major component in undergraduate training. Students with a negative attitude to working as GPs were also negative to having a major component of general practice in undergraduate training. Medical students with a positive stated attitude towards becoming GPs support changes in undergraduate training to include more general practice. The risk of increasing a negative attitude should be considered when changes are discussed.

  12. How can educators support general practice (GP) trainees to develop resilience to prevent burnout?

    Science.gov (United States)

    Sales, Bryony; Macdonald, Alexandra; Scallan, Samantha; Crane, Sue

    2016-11-01

    Burnout impacts adversely on professional and personal life, and holds implications for patient care. Current research on burnout mainly focuses on established general practitioners but it is unclear how early the signs of burnout really start. This work seeks to identify whether specific GP trainee groups are particularly at risk of burnout and the aspects of training they find stressful. A longitudinal cohort study, collecting qualitative and quantitative data through a single mode of data collection (questionnaire) took place with trainees from all GP training years (ST1-3), across a vocational training scheme (n = 48). Data gathered included the Oldenburg Burnout Inventory (OLBI). Higher than anticipated levels of burnout were displayed by all trainees. A sub-group self reporting higher levels of burnout comprised all-female, UK-trained-at-undergraduate GP trainees, with a partner but no children. Top reported stressors included knowledge/uncertainty, workload/time pressures and ePortfolio. Less than 50% of trainees perceived their burnout levels to be as high as their OLBI showing potential lack of insight. This research demonstrates that high levels of burnout are experienced in GP trainees as early as the first year of training. Early identification of burnout amongst trainees is essential by GP educators to help protect the future GP workforce.

  13. The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

    Science.gov (United States)

    Alvares, Stacy M.; Dunn, Clarence A.; Brown, Tod A.; Wayner, Elizabeth E.; Carter, William G.

    2008-01-01

    Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and Detergent-Resistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals- possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior. PMID:18269919

  14. Cloning, expression and preliminary crystallographic analysis of the equine infectious anaemia virus (EIAV) gp45 ectodomain

    International Nuclear Information System (INIS)

    Sun, Pei-Long; Lv, Shu-Xia; Zhou, Jian-Hua; Liu, Xin-Qi

    2011-01-01

    The equine infectious anaemia virus gp45 ectodomain was cloned, expressed and crystallized. Preliminary crystallographic analysis showed that the protein belonged to space group P6 3 and contained one molecule per asymmetric unit. Like human immunodeficiency virus (HIV), equine infectious anaemia virus (EIAV) belongs to the lentivirus genus. The first successful lentiviral vaccine was developed for EIAV. Thus, EIAV may serve as a valuable model for HIV vaccine research. EIAV glycoprotein 45 (gp45) plays a similar role to gp41 in HIV by mediating virus–host membrane fusion. The gp45 ectodomain was constructed according to the structure of HIV gp41, with removal of the disulfide-bond loop region. The protein was expressed in Escherichia coli and crystallized following purification. However, most of the crystals grew as aggregates and could not be used for data collection. By extensively screening hundreds of crystals, a 2.7 Å resolution data set was collected from a single crystal. The crystal belonged to space group P6 3 , with unit-cell parameters a = b = 46.84, c = 101.61 Å, α = β = 90, γ = 120°. Molecular replacement was performed using the coordinates of various lengths of HIV gp41 as search models. A long bent helix was identified and a well defined electron-density map around the long helix was obtained. This primary model provided the starting point for further refinement

  15. A review of a GP registrar-run mobile health clinic for homeless people.

    Science.gov (United States)

    O'Carroll, A; Irving, N; O'Neill, J; Flanagan, E

    2017-08-01

    Homeless people have excessively high morbidity and mortality rates, yet they face barriers accessing primary care. A mobile health clinic, staffed by GP registrars, was developed to provide services to homeless people, particularly rough sleepers and sex workers. The aims were to improve access to primary care and to challenge the stereotypes and prejudices of GP registrars through direct contact with homeless people. This was a qualitative study; questionnaires were completed on the mobile health clinic and two focus groups were conducted. All service users were asked to complete a questionnaire over a 3 month period. Two focus groups were conducted with 6 and 14 GP registrars who had worked on the bus. There was an 80% response rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no way to access the free primary care to which they are entitled. Had the clinic not been available, over half would not have sought further treatment and 16% would have gone to an Emergency Department. Ninety-one percent of users rated the service 10/10. The focus groups found that GP registrars who worked on the mobile health clinic had decreased negative stereotypes, increased empathy, and more knowledge of homeless issues. Furthermore, they intended to ensure that homeless people will not face discrimination in their future practice. A GP Registrar-run Mobile Health Clinic achieved its aims of improving access to primary care for rough sleepers and sex workers, and challenging stereotypes of GP Registrars.

  16. Introducing a GP copayment in Australia: Who would carry the cost burden?

    Science.gov (United States)

    Elkins, Rosemary Kate; Schurer, Stefanie

    2017-05-01

    Recent policy changes designed to contain unsustainable health expenditure growth imply that many more Australians may soon be charged a copayment to consult a GP. We explore the distributional consequences associated with a range of hypothetical GP copayment scenarios using nationally-representative Australian survey data. For each scenario, we estimate the cost burden that individuals and households across the income distribution would need to absorb to maintain their current GP service utilisation. Even when concessional patients are charged a third or a quarter of the non-concessional copayment rate, the average estimated cost burden in the lowest income quartile is typically between three and six times that of the highest, and the average cost burden for women is significantly higher than for men within every income quartile. These disparities are intensified for those with a chronic illness. We conclude that the widespread implementation of GP copayments would disproportionately burden lower-income families, who experience higher rates of chronic illness, higher demand for GP services, and lower capacity to absorb price increases. The regressive nature of GP copayments is reduced when concessional and child patients are exempted entirely, highlighting the importance of supporting GPs-particularly in disadvantaged areas-to maintain bulk-billing arrangements for vulnerable patient groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. New CERN Health Insurance Scheme (CHIS) forms

    CERN Multimedia

    HR Department

    2015-01-01

    New versions of the following forms for claims and requests to the CERN Health Insurance Scheme (CHIS) have been released:   form for claiming reimbursement of medical expenses,   form for requesting advance reimbursement, and   dental estimate form (for treatments foreseen to exceed 800 CHF).   The new forms are available in French and English. They can either be completed electronically before being printed and signed, or completed in paper form. New detailed instructions can be found at the back of the claim form; CHIS members are invited to read them carefully. The electronic versions (PDF) of all the forms are available on the CHIS website and on the UNIQA Member Portal. CHIS Members are requested to use these new forms forthwith and to discard any previous version. Questions regarding the above should be addressed directly to UNIQA (72730 or 022.718 63 00 or uniqa.assurances@cern.ch).

  18. 'Just a GP': a mixed method study of undermining of general practice as a career choice in the UK.

    Science.gov (United States)

    Alberti, Hugh; Banner, Kimberley; Collingwood, Helen; Merritt, Kymberlee

    2017-11-03

    Failure to recruit sufficient applicants to general practice (GP) training has been a problem both nationally and internationally for many years and undermining of GP is one possible contributing factor. The aim of our study was to ascertain what comments, both negative and positive, are being made in UK clinical settings to GP trainees about GP and to further explore these comments and their influence on career choice. We conducted a mixed methods study. We surveyed all foundation doctors and GP trainees within one region of Health Education England regarding any comments they experienced relating to a career in GP. We also conducted six focus groups with early GP trainees to discuss any comments that they experienced and whether these comments had any influence on their or others career choice. Positive comments reported by trainees centred around the concept that choosing GP is a positive, family-focused choice which facilities a good work-life balance. Workload was the most common negative comment, alongside the notion of being 'just a GP'; the belief that GP is boring, a waste of training and a second-class career choice. The reasons for and origin of the comments are multifactorial in nature. Thematic analysis of the focus groups identified key factors such as previous exposure to and experience of GP, family members who were GPs, GP role models, demographics of the clinician and referral behaviour. Trainees perceived that negative comments may be discouraging others from choosing GP as a career. Our study demonstrates that negative comments towards GP as a career do exist within clinical settings and are having a potential impact on poor recruitment rates to GP training. We have identified areas in which further negative comments could be prevented by changing perceptions of GP as a career. Additional time spent in GP as undergraduates and postgraduates, and positive GP role models, could particularly benefit recruitment. We recommend that undermining of GP

  19. 77 FR 23735 - Agency Information Collection Activities: Forms G-1041 and G-1041A, Extension of a Currently...

    Science.gov (United States)

    2012-04-20

    ..., Genealogy Index Search Request and Genealogy Records Request. The Department of Homeland Security, U.S... existing information collection. (2) Title of the Form/Collection: Genealogy Index Search Request and Genealogy Records Request. (3) Agency form number, if any, and the applicable component of the Department of...

  20. 77 FR 44641 - Critical Infrastructure Private Sector Clearance Program Request

    Science.gov (United States)

    2012-07-30

    .... DHS Sector Specialists or Protective Security Advisors email the form to the individual who then... clearance request form is signed by both the Federal official who nominated the applicant and the Assistant...

  1. 78 FR 18988 - Agency Information Collection Activities; Proposed Collection; Comment Request

    Science.gov (United States)

    2013-03-28

    ... techniques or other forms of information technology to minimize the information collection burden. Information Collection Request Title: The Health Education Assistance Loan (HEAL) Program: Physician's... Information Collection Activities; Proposed Collection; Comment Request ACTION: Notice. SUMMARY: In compliance...

  2. 78 FR 27241 - Agency Information Collection Activities; Proposed Collection: Comment Request

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    2013-05-09

    ... Benefits Form and Instructions have been revised to remove the request for a social security number, update... new category of survivors was added under the PSOB Program. Approval is requested for new mechanisms...

  3. 76 FR 59379 - Proposed Information Collection; Comment Request; Generic Clearance for Research in Development...

    Science.gov (United States)

    2011-09-26

    ...-XXXX. Type of Review: Generic Clearance Request. Title: Generic Clearance for Research in Development... information collected through qualitative evaluation methods will inform the disclosure form's design and... Proposed Information Collection; Comment Request; Generic Clearance for Research in Development of...

  4. 75 FR 31745 - Notice of Request for Approval of an Information Collection; National Veterinary Services...

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    2010-06-04

    ...] Notice of Request for Approval of an Information Collection; National Veterinary Services Laboratories... collection associated with the National Veterinary Services Laboratories animal health diagnostic system...: For information on request forms associated with the National Veterinary Services Laboratories animal...

  5. Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

    Directory of Open Access Journals (Sweden)

    Annie Albin Lumen

    Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

  6. 49 CFR 191.19 - Report forms.

    Science.gov (United States)

    2010-10-01

    ... forms. Copies of the prescribed report forms are available without charge upon request from the address... 49 Transportation 3 2010-10-01 2010-10-01 false Report forms. 191.19 Section 191.19 Transportation... size and kind of paper. In addition, the information required by these forms may be submitted by any...

  7. 'I need her to be a doctor': patients' experiences of presenting health information from the internet in GP consultations.

    Science.gov (United States)

    Bowes, Parvathy; Stevenson, Fiona; Ahluwalia, Sanjiv; Murray, Elizabeth

    2012-11-01

    Patients are increasingly using the internet for health-related information and may bring this to a GP consultation. There is scant information about why patients do this and what they expect from their GP. The aim was to explore patients' motivation in presenting information, their perception of the GP's response and what they wanted from their doctor. Qualitative study based in North London involving patients with experience of bringing health information from the internet to their GP. Semi-structured face-to-face and telephone interviews using a critical incident technique, recorded, transcribed verbatim, and subjected to thematic analysis by a multidisciplinary team of researchers. Twenty-six interviews were completed. Participants reported using the internet to become better informed about their health and hence make best use of the limited time available with the GP and to enable the GP to take their problem more seriously. Patients expected their GP to acknowledge the information; discuss, explain, or contextualise it; and offer a professional opinion. Patients tended to prioritise the GP opinion over the internet information. However, if the GP appeared disinterested, dismissive or patronising patients reported damage to the doctor-patient relationship, occasionally to the extent of seeking a second opinion or changing their doctor. This is the first in-depth qualitative study to explore why patients present internet information to their GP within the consultation and what they want when they do this. This information should help GPs respond appropriately in such circumstances.

  8. CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2013-12-01

    Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

  9. Conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope

    International Nuclear Information System (INIS)

    Palker, T.J.; Matthews, T.J.; Clark, M.E.

    1987-01-01

    A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV + patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did react in RIA and neutralized HIV in vitro. Thus, ≅ 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays

  10. Gp120 stability on HIV-1 virions and Gag-Env pseudovirions is enhanced by an uncleaved Gag core

    International Nuclear Information System (INIS)

    Hammonds, Jason; Chen Xuemin; Ding Lingmei; Fouts, Timothy; De Vico, Anthony; Megede, Jan zur; Barnett, Susan; Spearman, Paul

    2003-01-01

    Human immunodeficiency virus type-1 (HIV-1) particles incorporate a trimeric envelope complex (Env) made of gp120 (SU) and gp41 (TM) heterodimers. It has been previously established that soluble CD4 (sCD4) interaction leads to shedding of gp120 from viral particles, and that gp120 may also be easily lost from virions during incubation or particle purification procedures. In the design of HIV particle or pseudovirion-based HIV vaccines, it may be important to develop strategies to maximize the gp120 content of particles. We analyzed the gp120 retention of HIV-1 laboratory-adapted isolates and primary isolates following incubation with sCD4 and variations in temperature. NL4-3 shed gp120 readily in a temperature- and sCD4-dependent manner. Surprisingly, inactivation of the viral protease led to markedly reduced shedding of gp120. Gp120 shedding was shown to vary markedly between HIV-1 strains, and was not strictly determined by whether the isolate was adapted to growth on immortalized T cell lines or was a primary isolate. Pseudovirions produced by expression of codon-optimized gag and env genes also demonstrated enhanced gp120 retention when an immature core structure was maintained. Pseudovirions of optimal stability were produced through a combination of an immature Gag protein core and a primary isolate Env. These results support the feasibility of utilizing pseudovirion particles as immunogens for the induction of humoral responses directed against native envelope structures

  11. Clinicopathological correlations of podoplanin (gp38 expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.

    Directory of Open Access Journals (Sweden)

    Manuel J Del Rey

    Full Text Available Synovial fibroblasts (SF undergo phenotypic changes in rheumatoid arthritis (RA that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38 expression by RA SF.Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk.gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN, and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction.In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.

  12. Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

    Directory of Open Access Journals (Sweden)

    Shoufeng Ren

    2018-01-01

    Full Text Available Ebola virus (EBOV causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP is the major protective antigen of EBOV, and can generate virus-like particles (VLPs by co-expression with matrix protein (VP40. In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV replicon vector DREP to express EBOV GP and matrix viral protein (VP40. EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40. Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.

  13. 75 FR 16874 - Proposed Collection; Comment Request

    Science.gov (United States)

    2010-04-02

    ..., including the use of automated collection techniques or other forms of information technology. 1. Title and...-5I, Letter to Non-Railroad Employers on Employment and Earnings of a Claimant; Form ID-5R(SUP... Regarding Benefit Claim for Days of Employment. Completion is voluntary. One response is requested of each...

  14. 77 FR 55900 - Proposed Collection; Comment Request

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    2012-09-11

    ... benchmark survey (Form SHC) of all significant U.S.-resident custodians and end-investors is conducted every... the very largest U.S.-resident custodians and end- investors. The data requested in Form SHCA will... Review: Extension of a currently approved data collection. Affected Public: Business/Financial...

  15. The conserved residue Arg46 in the N-terminal heptad repeat domain of HIV-1 gp41 is critical for viral fusion and entry.

    Directory of Open Access Journals (Sweden)

    Xiaoyi Wang

    Full Text Available During the process of HIV-1 fusion with the target cell, the N-terminal heptad repeat (NHR of gp41 interacts with the C-terminal heptad repeat (CHR to form fusogenic six-helix bundle (6-HB core. We previously identified a crucial residue for 6-HB formation and virus entry--Lys63 (K63 in the C-terminal region of NHR (aa 54-70, which forms a hydrophobic cavity. It can form an important salt bridge with Asp121 (D121 in gp41 CHR. Here, we found another important conserved residue for virus fusion and entry, Arg46 (R46, in the N-terminal region of NHR (aa 35-53, which forms a hydrogen bond with a polar residue, Asn43 (N43, in NHR, as a part of the hydrogen-bond network. R46 can also form a salt bridge with a negatively charged residue, Glu137 (E137, in gp41 CHR. Substitution of R46 with the hydrophobic residue Ala (R46A or the negatively charged residue Glu (R46E resulted in disruption of the hydrogen bond network, breakage of the salt bridge and reduction of 6-HB's stability, leading to impairment of viral fusion and decreased inhibition of N36, an NHR peptide. Similarly, CHR peptide C34 with substitution of E137 for Ala (E137A or Arg (E137R also exhibited reduced inhibitory activity against HIV-1 infection and HIV-1-mediated cell-to-cell fusion. These results suggest that the positively charged residue R46 and its hydrogen bond network, together with the salt bridge between R46 and E137, are important for viral fusion and entry and may therefore serve as a target for designing novel HIV fusion/entry inhibitors.

  16. Mutations in gp41 are correlated with coreceptor tropism but do not improve prediction methods substantially.

    Science.gov (United States)

    Thielen, Alexander; Lengauer, Thomas; Swenson, Luke C; Dong, Winnie W Y; McGovern, Rachel A; Lewis, Marilyn; James, Ian; Heera, Jayvant; Valdez, Hernan; Harrigan, P Richard

    2011-01-01

    The main determinants of HIV-1 coreceptor usage are located in the V3-loop of gp120, although mutations in V2 and gp41 are also known. Incorporation of V2 is known to improve prediction algorithms; however, this has not been confirmed for gp41 mutations. Samples with V3 and gp41 genotypes and Trofile assay (Monogram Biosciences, South San Francisco, CA, USA) results were taken from the HOMER cohort (n=444) and from patients screened for the MOTIVATE studies (n=1,916; 859 with maraviroc outcome data). Correlations of mutations with tropism were assessed using Fisher's exact test and prediction models trained using support vector machines. Models were validated by cross-validation, by testing models from one dataset on the other, and by analysing virological outcome. Several mutations within gp41 were highly significant for CXCR4 usage; most strikingly an insertion occurring in 7.7% of HOMER-R5 and 46.3% of HOMER-X4 samples (MOTIVATE 5.7% and 25.2%, respectively). Models trained on gp41 sequence alone achieved relatively high areas under the receiver-operating characteristic curve (AUCs; HOMER 0.713 and MOTIVATE 0.736) that were almost as good as V3 models (0.773 and 0.884, respectively). However, combining the two regions improved predictions only marginally (0.813 and 0.902, respectively). Similar results were found when models were trained on HOMER and validated on MOTIVATE or vice versa. The difference in median log viral load decrease at week 24 between patients with R5 and X4 virus was 1.65 (HOMER 2.45 and MOTIVATE 0.79) for V3 models, 1.59 for gp41-models (2.42 and 0.83, respectively) and 1.58 for the combined predictor (2.44 and 0.86, respectively). Several mutations within gp41 showed strong correlation with tropism in two independent datasets. However, incorporating gp41 mutations into prediction models is not mandatory because they do not improve substantially on models trained on V3 sequences alone.

  17. P-gp expression in brown trout erythrocytes: evidence of a detoxification mechanism in fish erythrocytes.

    Science.gov (United States)

    Valton, Emeline; Amblard, Christian; Wawrzyniak, Ivan; Penault-Llorca, Frederique; Bamdad, Mahchid

    2013-12-05

    Blood is a site of physiological transport for a great variety of molecules, including xenobiotics. Blood cells in aquatic vertebrates, such as fish, are directly exposed to aquatic pollution. P-gp are ubiquitous "membrane detoxification proteins" implicated in the cellular efflux of various xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which may be pollutants. The existence of this P-gp detoxification system inducible by benzo [a] pyrene (BaP), a highly cytotoxic PAH, was investigated in the nucleated erythrocytes of brown trout. Western blot analysis showed the expression of a 140-kDa P-gp in trout erythrocytes. Primary cultures of erythrocytes exposed to increasing concentrations of BaP showed no evidence of cell toxicity. Yet, in the same BaP-treated erythrocytes, P-gp expression increased significantly in a dose-dependent manner. Brown trout P-gp erythrocytes act as membrane defence mechanism against the pollutant, a property that can be exploited for future biomarker development to monitor water quality.

  18. GP and pharmacist inter-professional learning - a grounded theory study.

    Science.gov (United States)

    Cunningham, David E; Ferguson, Julie; Wakeling, Judy; Zlotos, Leon; Power, Ailsa

    2016-05-01

    Practice Based Small Group Learning (PBSGL) is an established learning resource for primary care clinicians in Scotland and is used by one-third of general practitioners (GPs). Scottish Government and UK professional bodies have called for GPs and pharmacists to work more closely together to improve care. To gain GPs' and pharmacists' perceptions and experiences of learning together in an inter-professional PBSGL pilot. Qualitative research methods involving established GP PBSGL groups in NHS Scotland recruiting one or two pharmacists to join them. A grounded theory method was used. GPs were interviewed in focus groups by a fellow GP, and pharmacists were interviewed individually by two researchers, neither being a GP or a pharmacist. Interviews were audio-recorded, transcribed and analysed using grounded theory methods. Data saturation was achieved and confirmed. Three themes were identified: GPs' and pharmacists' perceptions and experiences of inter-professional learning; Inter-professional relationships and team-working; Group identity and purpose of existing GP groups. Pharmacists were welcomed into GP groups and both professions valued inter-professional PBSGL learning. Participants learned from each other and both professions gained a wider perspective of the NHS and of each others' roles in the organisation. Inter-professional relationships, communication and team-working were strengthened and professionals regarded each other as peers and friends.

  19. Comparative Glycoprofiling of HIV gp120 Immunogens by Capillary Electrophoresis and MALDI Mass Spectrometry

    Science.gov (United States)

    Guttman, Miklós; Váradi, Csaba; Lee, Kelly K.; Guttman, András

    2015-01-01

    The Human Immunodeficiency Virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. Vaccine trials with the gp120 subunit of Env are ongoing with the recent RV144 trial showing moderate efficacy. gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by capillary electrophoresis with laser induced fluorescence detection and MALDI-MS. The glycosylation profiles were found to be similar for chronic vs. transmitter/founder isolates and only varied moderately between gp120s from different clades. This study revealed that the addition of specific tags, such as the gD tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. PMID:25809283

  20. Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice.

    Science.gov (United States)

    Durova, Oxana M; Vorobiev, Ivan I; Smirnov, Ivan V; Reshetnyak, Andrew V; Telegin, Georgy B; Shamborant, Olga G; Orlova, Nadezda A; Genkin, Dmitry D; Bacon, Andrew; Ponomarenko, Natalia A; Friboulet, Alain; Gabibov, Alexander G

    2009-11-01

    Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4(+) receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production "catalytic vaccine". Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.

  1. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

    International Nuclear Information System (INIS)

    Arthur, L.O.; Pyle, S.W.; Nara, P.L.

    1987-01-01

    The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4 + and T8 + cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4 + cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo

  2. Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

    DEFF Research Database (Denmark)

    Sørensen, A L; Hey, A S; Kharazmi, A

    1994-01-01

    In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

  3. 65 nm LP/GP mix low cost platform for multi-media wireless and consumer applications

    Science.gov (United States)

    Tavel, B.; Duriez, B.; Gwoziecki, R.; Basso, M. T.; Julien, C.; Ortolland, C.; Laplanche, Y.; Fox, R.; Sabouret, E.; Detcheverry, C.; Boeuf, F.; Morin, P.; Barge, D.; Bidaud, M.; Biénacel, J.; Garnier, P.; Cooper, K.; Chapon, J. D.; Trouiller, Y.; Belledent, J.; Broekaart, M.; Gouraud, P.; Denais, M.; Huard, V.; Rochereau, K.; Difrenza, R.; Planes, N.; Marin, M.; Boret, S.; Gloria, D.; Vanbergue, S.; Abramowitz, P.; Vishnubhotla, L.; Reber, D.; Stolk, P.; Woo, M.; Arnaud, F.

    2006-04-01

    A complete 65 nm CMOS platform, called LP/GP Mix, has been developed employing thick oxide transistor (IO), Low Power (LP) and General Purpose (GP) devices on the same chip. Dedicated to wireless multi-media and consumer applications, this new triple gate oxide platform is low cost (+1mask only) and saves over 35% of dynamic power with the use of the low operating voltage GP. The LP/GP mix shows competitive digital performance with a ring oscillator (FO = 1) speed equal to 7 ps per stage (GP) and 6T-SRAM static power lower than 10 pA/cell (LP). Compatible with mixed-signal design requirements, transistors show high voltage gain, low mismatch factor and low flicker noise. Moreover, to address mobile phone demands, excellent RF performance has been achieved with FT = 160 GHz for LP and 280 GHz for GP nMOS transistors.

  4. Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

    Science.gov (United States)

    Dielissen, Patrick W; Bottema, Ben JAM; Verdonk, Petra; Lagro-Janssen, Toine LM

    2009-01-01

    Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness. PMID:19737396

  5. Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

    Directory of Open Access Journals (Sweden)

    Lagro-Janssen Toine LM

    2009-09-01

    Full Text Available Abstract Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness.

  6. Medical students' and GP registrars' accommodation needs in the rural community: insight from a Victorian study.

    Science.gov (United States)

    Han, Gil-Soo; Wearne, Ben; O'Meara, Peter; McGrail, Matthew; Chesters, Janice

    2003-01-01

    Medical education in Australia is currently entering a new era, including support for the significant extension of medical students and general practitioner (GP) registrars' training programs in rural communities. This commitment to rural medical student and general practitioner recruitment and retention has made the provision of accommodation in rural communities a vital issue. This study has found that approximately half of all medical students on placement with rural GPs are currently accommodated with their GP supervisor or with other practice staff. This is a burden for many GPs and when the anticipated increase in the frequency and length of rural placements occurs what is currently a burden will become unsustainable. The changing gender and cultural demographics of medical students and rural general practitioners will also contribute to stresses on this accommodation system. It is important to have a systematic approach towards more appropriate and sustainable models of accommodation for both medical students and GP registrars.

  7. Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology

    Directory of Open Access Journals (Sweden)

    Harty Ronald N

    2006-05-01

    Full Text Available Abstract Recently we described a role for Ebola virus proteins, NP, GP, and VP35 in enhancement of VP40 VLP budding. To explore the possibility that VLP structure was altered by co-expression of EBOV proteins leading to the observed enhancement of VP40 VLP budding, we performed density gradient analysis as well as electron microscopy studies. Our data suggest that VP40 is the major determinant of VLP morphology, as co-expression of NP, GP and VP35 did not significantly change VLP density, length, and diameter. Ultra-structural changes were noted in the core of the VLPs when NP was co-expressed with VP40. Overall, these findings indicate that major changes in morphology of VP40 VLPs were likely not responsible for enhanced budding of VP40 VLPs in the presence of GP, NP and/or VP35.

  8. Influences on GP coping and resilience: a qualitative study in primary care.

    Science.gov (United States)

    Cheshire, Anna; Ridge, Damien; Hughes, John; Peters, David; Panagioti, Maria; Simon, Chantal; Lewith, George

    2017-06-01

    'Neoliberal' work policies, austerity, NHS restructuring, and increased GP consultation rates provide the backdrop against increasing reports of GP burnout and an impending shortage of GPs. To explore GPs' experiences of workplace challenges and stresses, and their coping strategies, particularly focusing on understanding the impact of recent NHS workplace change. Study design was qualitative, with data collected from two focus groups and seven one-to-one telephone interviews. Focus groups and one-to-one telephone interviews explored the experiences of GPs currently practising in England, recruited through convenience sampling. Data were collected using a semi-structured interview approach and analysed using thematic analysis. There were 22 GP participants recruited: focus groups ( n = 15) and interviews ( n = 7). Interviewees understood GPs to be under intense and historically unprecedented pressures, which were tied to the contexts in which they work, with important moral implications for 'good' doctoring. Many reported that being a full-time GP was too stressful: work-related stress led to mood changes, sleep disruption, increases in anxiety, and tensions with loved ones. Some had subsequently sought ways to downsize their clinical workload. Workplace change resulted in little time for the things that helped GP resilience: a good work-life balance and better contact with colleagues. Although some GPs were coping better than others, GPs acknowledged that there was only so much an individual GP could do to manage their stress, given the external work issues they faced. GPs experience their emotional lives and stresses as being meaningfully shaped by NHS factors. To support GPs to provide effective care, resilience building should move beyond the individual to include systemic work issues. © British Journal of General Practice 2017.

  9. Contributor Form

    Directory of Open Access Journals (Sweden)

    Chief Editor

    2014-09-01

    to produce preprints or reprints and translate into languages other than English for sale or free distribution; and 4 the right to republish the work in a collection of articles in any other mechanical or electronic format. We give the rights to the corresponding author to make necessary changes as per the request of the journal, do the rest of the correspondence on our behalf and he/she will act as the guarantor for the manuscript on our behalf. All persons who have made substantial contributions to the work reported in the manuscript, but who are not contributors, are named in the Acknowledgment and have given me/us their written permission to be named. If I/we do not include an Acknowledgment that means I/we have not received substantial contributions from non-contributors and no contributor has been omitted.S NoAuthors' NamesContribution (IJCME Guidelines{1 substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; 2 drafting the article or revising it critically for important intellectual content; and 3 final approval of the version to be published. Authors should meet conditions 1, 2, and 3}.SignatureDate                              Note: All the authors are required to sign independently in this form in the sequence given above. In case an author has left the institution/country and whose whereabouts are not known, the senior author may sign on his/her behalf taking the responsibility.No addition/deletion/ or any change in the sequence of the authorship will be permissible at a later stage, without valid reasons and permission of the Editor.If the authorship is contested at any stage, the article will be either returned or will not be processed for publication till the issue is solved.Maximum up to 4 authors for short communication and up to 6 authors for original article.

  10. Contributors Form

    Directory of Open Access Journals (Sweden)

    Chief Editor

    2016-06-01

    to produce preprints or reprints and translate into languages other than English for sale or free distribution; and 4 the right to republish the work in a collection of articles in any other mechanical or electronic format. We give the rights to the corresponding author to make necessary changes as per the request of the journal, do the rest of the correspondence on our behalf and he/she will act as the guarantor for the manuscript on our behalf. All persons who have made substantial contributions to the work reported in the manuscript, but who are not contributors, are named in the Acknowledgment and have given me/us their written permission to be named. If I/we do not include an Acknowledgment that means I/we have not received substantial contributions from non-contributors and no contributor has been omitted.S NoAuthors' NamesContribution (IJCME Guidelines{1 substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; 2 drafting the article or revising it critically for important intellectual content; and 3 final approval of the version to be published. Authors should meet conditions 1, 2, and 3}.SignatureDate                              Note: All the authors are required to sign independently in this form in the sequence given above. In case an author has left the institution/country and whose whereabouts are not known, the senior author may sign on his/her behalf taking the responsibility.No addition/deletion/ or any change in the sequence of the authorship will be permissible at a later stage, without valid reasons and permission of the Editor.If the authorship is contested at any stage, the article will be either returned or will not be processed for publication till the issue is solved.Maximum up to 4 authors for short communication and up to 6 authors for original article.

  11. 76 FR 44965 - Notice of Revision of Standard Forms 39 and 39-A

    Science.gov (United States)

    2011-07-27

    ... OFFICE OF PERSONNEL MANAGEMENT Notice of Revision of Standard Forms 39 and 39-A AGENCY: U.S... Management (OPM) has revised Standard Form (SF) 39, Request For Referral Of Eligibles, and SF 39-A, Request... part 332. The SF 39 outlines instructions to be used by hiring officials to request a list of eligible...

  12. Family effects on the rurality of GP's work location: a longitudinal panel study.

    Science.gov (United States)

    McGrail, Matthew R; Russell, Deborah J; O'Sullivan, Belinda G

    2017-10-19

    Reduced opportunities for children's schooling and spouse's/partner's employment are identified internationally as key barriers to general practitioners (GPs) working rurally. This paper aims to measure longitudinal associations between the rurality of GP work location and having (i) school-aged children and (ii) a spouse/partner in the workforce. Participants included 4377 GPs responding to at least two consecutive annual surveys of the Medicine in Australia: Balancing Employment and Life (MABEL) national longitudinal study between 2008 and 2014. The main outcome, GP work location, was categorised by remoteness and population size. Five sequential binary school-age groupings were defined according to whether a GP had no children, only preschool children (aged 0-4 years), at least one primary-school child (aged 5-11 years), at least one child in secondary school (aged 12-18 years), and all children older than secondary school (aged ≥ 19). Partner in the workforce was defined by whether a GP had a partner who was either currently working or looking for work, or not. Separate generalised estimating equation models, which aggregated consecutive annual observations per GP, tested associations between work location and (i) educational stages and (ii) partner employment, after adjusting for key covariates. Male GPs with children in secondary school were significantly less likely to work rurally (inclusive of > 50 000 regional centres through to the smallest rural towns of locations were not significantly associated with the educational stage of their children. Having a partner in the workforce was not associated with work location for male GPs, whereas female GPs with a partner in the workforce were significantly less likely to work in smaller rural/remote communities (location is related to key family needs which differ according to GP gender and educational stages of children. Such non-professional factors are likely to be dynamic across the GP's lifespan and

  13. Gravity Probe-B (GP-B) Mission and Tracking, Telemetry and Control Subsystem Overview

    Science.gov (United States)

    Kennedy, Paul; Bell, Joseph L. (Technical Monitor)

    2001-01-01

    The National Aeronautics and Space Administration's (NASA) Marshall Space Flight Center (MSFC) in Huntsville, Alabama will launch the Gravity Probe B (GP-B) space experiment in the Fall of 2002. The GP-B spacecraft was developed to prove Einstein's theory of General Relativity. This paper will provide an overview of the GPB mission and will discuss the design, and test of the spacecraft Tracking, Telemetry and Control (TT&C) subsystem which incorporates NASA's latest generation standard transponder for use with the NASA Tracking and Data Relay Satellite System (TDRSS).

  14. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Directory of Open Access Journals (Sweden)

    Beuy Joob

    2014-12-01

    Full Text Available The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present. Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus. The in-depth analysis of the viral protein to find the binding site, active pocket is needed. Here, the authors analyzed the envelope glycoprotein GP2 from Ebola virus. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus was done. According to this assessment, 7 active pockets with varied druggability could be identified.

  15. Council tax valuation bands and contacts with a GP out-of-hours service.

    Science.gov (United States)

    Beale, Norman; Taylor, Gordon; Gwynne, Mark; Peart, Carole

    2006-04-01

    UK GPs are no longer responsible for the organisation of out-of-hours care for their patients, but resources remains capitation-based. This cross-sectional study tests whether council tax valuation bands can predict the demand for such services. All out-of-hours contacts made by patients in North Wiltshire over 4 months were classified by council tax band; frequencies compared with official population statistics. Council tax band predicts out-of-hours GP workload irrespective of age and sex: the more modest the home, the higher the GP contact rate. It may prove more difficult to sustain out-of-hours services in deprived parts of the UK.

  16. 76 FR 49769 - Proposed Agency Information Collection Activities; Comment Request

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    2011-08-11

    ... in Organizational Structure. Agency form number: FR Y-10E. OMB control number: 7100-0297. Frequency... OMB control numbers to collection of information requests and requirements conducted or sponsored by... control number. Request for Comment on Information Collection Proposal The following information...

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    2012-07-03

    ...), Office of Refugee Resettlement (ORR), is requesting the information from Form ORR-6 to determine the..., budget requests, and assistance policies. ORR regulations require that State Refugee Resettlement and... above-mentioned programs. Respondents: State Refugee Resettlement and Wilson-Fish Agencies, local, and...

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    2010-04-08

    ...), Office of Refugee Resettlement (ORR), is requesting the information from Form ORR-6 to determine the..., budget requests, and assistance policies. ORR regulations require that State Refugee Resettlement and... above-mentioned programs. Respondents: State Refugee Resettlement and Wilson-Fish Agencies, local, and...

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    2012-09-14

    ... FEDERAL MEDIATION AND CONCILIATION SERVICE Labor-Management Relations Information Collection... the following public information collection request (ICR) to the Office of Management and Budget (OMB... information collection request is the Notice to Mediation Agencies (Agency Form F-7), OMB control number 3076...

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    2012-12-26

    ... . Title: Request for Release of Lien and/or Approval of Sale. OMB Control Number: 0572-0041. Type of... security instruments, e.g., the RUS mortgage, limit the rights of a RUS borrower to dispose of its capital assets. The RUS Form 793, Request for Release of Lien and/or Approval of Sale, allows the...

  1. Audit of Radiological requests at the University of Nigeria Teaching ...

    African Journals Online (AJOL)

    Results: Important items like section for safety information for examinations involving contrast agent administration and purpose of the radiological request were omissions noted in the request form currently in use at UNTH. Among other non-compliances, column for patients age and sex though provided for, had no ...

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    2012-05-25

    ... others having knowledge to request substitutes securities or payment of lost, stolen or destroyed... of Purchase Price of United States Savings Bonds for Organizations. Form: PD F 5410. Abstract: Used by an organization to request refund of purchase price of United States Savings Bonds. Affected...

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    2010-07-06

    ... DEPARTMENT OF COMMERCE Submission for OMB Review; Comment Request The Department of Commerce will... Social Network Analysis. OMB Control Number: None. Form Number(s): None. Type of Request: Regular... on these issues in many capacities. A social network analysis will serve to identify the network of...

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    ... DEPARTMENT OF COMMERCE Submission for OMB Review; Comment Request The Department of Commerce will... Rationalization Social Study. OMB Control Number: 0648-0606. Form Number(s): NA. Type of Request: Regular... fishery. An understanding of social impacts in fisheries--achieved through the collection of data on...

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    ... information so that they can assess the performance of the investment vehicle or stock plan. Form 11-K is... SECURITIES AND EXCHANGE COMMISSION Submission for OMB Review; Comment Request Upon Written Request Copies Available From: Securities and Exchange Commission, Office of Investor Education and Advocacy...

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    ... information collection request may be found at www.reginfo.gov . Bureau of the Public Debt (BPD) OMB Number...: Revision of a currently approved collection. Title: Supporting Statement of Ownership for Overdue United States Bearer Securities. Form: PD F 1071. Abstract: Used to establish ownership and support a request...

  10. Immunodiagnosis of paracoccidioidomycosis due to Paracoccidioides brasiliensis using a latex test: detection of specific antibody anti-gp43 and specific antigen gp43.

    Directory of Open Access Journals (Sweden)

    Priscila Oliveira Dos Santos

    2015-02-01

    Full Text Available Paracoccidioidomycosis (PCM is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations.A latex immunoassay using sensitized latex particles (SLPs with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43 was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF, and bronchoalveolar lavage (BAL from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0, specificity (93.94%, 95% CI 87.3-97.7, and positive (91.4% and negative (98.9% predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6, specificity (88.89%, 95% CI 81.0-94.3, and positive (85.1% and negative (97.8% predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924 and mAb17c-SLPs (k = 0.850, which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy.The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure

  11. Up- and Down-Quark Contributions to the Nucleon Form Factors

    Directory of Open Access Journals (Sweden)

    Qattan I. A.

    2014-03-01

    Full Text Available Recent measurements of the neutron s electric to magnetic form factors ratio, Rn = µnGnE/GnM, up to 3.4 (GeV/c2 combined with existing Rp = µpGpE/GpM measurements in the same Q2 range allowed, for the first time, a separation of the up- and downquark contributions to the form factors at high Q2, as presented by Cates, et al.. Our analysis expands on the original work by including additional form factor data, applying two-photon exchange (TPE corrections, and accounting for the uncertainties associated with all of the form factor measurements.

  12. 75 FR 39620 - Proposed Information Collection (Dependents' Educational Assistance (DEA) Election Request...

    Science.gov (United States)

    2010-07-09

    ... (Dependents' Educational Assistance (DEA) Election Request) Activity: Comment Request AGENCY: Veterans... veterans beginning date to start their DEA benefits. DATES: Written comments and recommendations on the.... Title: Dependents' Educational Assistance (DEA) Election Request, VA Form Letter 22-909. OMB Control...

  13. 78 FR 17778 - Proposed Information Collection (Dependents' Educational Assistance (DEA) Election Request...

    Science.gov (United States)

    2013-03-22

    ... (Dependents' Educational Assistance (DEA) Election Request) Activity: Comment Request AGENCY: Veterans... veterans beginning date to start their DEA benefits. DATES: Written comments and recommendations on the.... Title: Dependents' Educational Assistance (DEA) Election Request, VA Form Letter 22-909. OMB Control...

  14. 32 CFR 1801.21 - Processing requests for access to or amendment of records.

    Science.gov (United States)

    2010-07-01

    ... NATIONAL COUNTERINTELLIGENCE CENTER PUBLIC RIGHTS UNDER THE PRIVACY ACT OF 1974 Action On Privacy Act... whether the requester cites one Act in the request, both, or neither. This action is taken in order to..., in the form of a final written response, shall so inform the requester and advise of his or her right...

  15. 78 FR 21617 - Notice of Proposed Information Collection: Comment Request; Final Endorsement of Credit Instrument

    Science.gov (United States)

    2013-04-11

    ... Information Collection: Comment Request; Final Endorsement of Credit Instrument AGENCY: Office of the... Proposal: Final Endorsement of Credit Instrument. OMB Control Number, if applicable: 2502-0016. Description... Endorsement of Credit Instrument'' form is used to request to request final endorsement by HUD of the credit...

  16. The Impact of the Proposed delta Gp Limits on Glass Formulation Efforts: Part II. Experimental Results

    International Nuclear Information System (INIS)

    PEELER, DAVID

    2004-01-01

    The Savannah River National Laboratory (SRNL) has initiated studies to assess alternative durability options that may provide access to compositional regions of interest in support of the accelerated cleanup mission at the Defense Waste Processing Facility (DWPF). One of the options being pursued is the redefinition of the durability model acceptability limits. Some of the conservative steps used in establishing the current limits without compromising the high confidence required for meeting the specification on the waste form quality were identified and eliminated. The results led to a set of three new Property Acceptability Region (PAR) values for the preliminary glass dissolution estimator that has the potential to allow access to compositional regions of interest to improve melt rate or waste loading. Although these limits are available for implementation, there is no driving force to do so with the current sludge batch (i.e., the current Frit 418 - Sludge Batch 3 (SB3) system is TL limited). The objectives of this task were to investigate (and generate) the incentive of applying the proposed durability limits in the Product Composition Control System (PCCS) from a glass formulation perspective. Glass compositions were identified or developed to transition into and through the region of GP acceptability as defined by the current and proposed durability limits. The progression through the newly defined acceptability region was accomplished by increasing the total alkali in the glass via higher alkali frits and/or waste loading (WL). The focus of this report is on the measured durability response as it compares to model predictions to assess the applicability and/or potential conservatism of the various limits or durability approaches. The normalized boron release values (NL [B] g/L) for the study glasses ranged from approximately 1.0 g/L to 2.0 g/L. The Product Consistency Test (PCT) responses provide evidence that implementation of the proposed GP limits will

  17. 78 FR 49592 - Agency Information Collection Activities: Proposed Request and Comment Request

    Science.gov (United States)

    2013-08-14

    ... respondents response (minutes) burden (hours) Paper form 37,500 1 10 6,250 In-person or telephone interview... initial intake interview including a request for consent from the participants, documented on a demonstration enrollment form. Local project staff will conduct these interviews at the local project sites, or...

  18. Small-angle scattering from GP zones in Al–Cu alloy

    Indian Academy of Sciences (India)

    Administrator

    ficial aging, which are extensively used in commercial practice. It is well established ... Cu system shows the variety of metastable states follow- ing the sequence SSS .... the model for spinodal decomposition of GP 1 zones in. Al–Cu system ...

  19. Study of coherence strain of GP II zones in an aged aluminum composite

    International Nuclear Information System (INIS)

    Hernández-Rivera, J.L.; Rivera, J.J. Cruz; Koch, C.T.; Özdöl, V.B.; Martínez-Sánchez, R.

    2012-01-01

    Highlights: ► Precipitation sequence was changed in 2024 Al alloy. ► Image artifacts ought to the mask size and shape increased the real strain value. ► The strain distribution around experimental GP area was non uniform and more complex than reference. ► The origin of this strain distribution are related to mechanisms by which GP precipitates lose coherence. - Abstract: Strain mapping using the geometric phase analysis (GPA) technique was applied to Al–GP II (Guinier–Preston) nanoscale precipitates, using both high resolution transmission electron microscopy (HRTEM) micrographs as well as the exit wave function (EWF) obtained by focal series reconstruction. The experimental strain results were compared with strain maps obtained from an atomic model which consisted of an Al supercell containing a GP II precipitate. It was built as a reference from literature data. The experimental results demonstrate a complex strain distribution and larger fluctuations than the reference strain maps. These differences were found to be partly a consequence of image artifacts produced by the technique as well as complex microstructural events which were present at the development stage studied.

  20. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    NARCIS (Netherlands)

    de Jong-Potjer, L. C.; Elsinga, J.; le Cessie, S.; van der Pal-de Bruin, K. M.; Neven, A. Knuistingh; Buitendijk, S. E.; Assendelft, W. J. J.

    2006-01-01

    BACKGROUND: Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. METHODS: Randomised trial of usual care versus

  1. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    NARCIS (Netherlands)

    Jong-Potjer, L.C. de; Elsinga, J.; Cessie, S. le; Pal-de Bruin, K.M. van der; Knuistingh Neven, A.; Buitendijk, S.E.; Assendelft, W.J.J.

    2006-01-01

    Background: Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. Methods: Randomised trial of usual care versus

  2. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    Directory of Open Access Journals (Sweden)

    Neven A Knuistingh

    2006-11-01

    Full Text Available Abstract Background Preconception counselling (PCC can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. Methods Randomised trial of usual care versus GP-initiated PCC for women aged 18–40, in 54 GP practices in the Netherlands. Women completed the six-item Spielberger State Trait Anxiety Inventory (STAI before PCC (STAI-1 and after (STAI-2. After pregnancy women completed a STAI focusing on the first trimester of pregnancy (STAI-3. Results The mean STAI-1-score (n = 466 was 36.4 (95% CI 35.4 – 37.3. Following PCC there was an average decrease of 3.6 points in anxiety-levels (95% CI, 2.4 – 4.8. Mean scores of the STAI-3 were 38.5 (95% CI 37.7 – 39.3 in the control group (n = 1090 and 38.7 (95% CI 37.9 – 39.5 in the intervention group (n = 1186. Conclusion PCC from one's own GP reduced anxiety after participation, without leading to an increase in anxiety among the intervention group during pregnancy. We therefore conclude that GPs can offer PCC to the general population without fear of causing anxiety. Trial Registration: ISRCTN53942912

  3. Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro

    DEFF Research Database (Denmark)

    Niemeier, A; Willnow, T; Dieplinger, H

    1999-01-01

    for both LRP and megalin/gp330 were compared with regard to their ability to bind, internalize, and degrade dioctadecyltetramethylindocarbocyanine perchlorate (DiI)-fluorescence-labeled Lp(a) as well as equimolar amounts of 125I-labeled Lp(a) and LDL. Uptake and degradation of radiolabeled Lp...

  4. Working as a locum GP: their professional role in organizational context.

    NARCIS (Netherlands)

    Batenburg, R.; Hassel, D. van; Velden, L. van der

    2012-01-01

    Context: The workforce of General Practitioners (GPs) in the Netherlands is closely monitored and planned to ensure their pivotal role in primary care and the Dutch health care system. While the majority of GPs have their own practice or are employed by other GP practices or health community

  5. Functional cloning of a gp100-reactive T-cell receptor from vitiligo patient skin

    NARCIS (Netherlands)

    Klarquist, Jared; Eby, Jonathan M.; Henning, Steven W.; Li, Mingli; Wainwright, Derek A.; Westerhof, Wiete; Luiten, Rosalie M.; Nishimura, Michael I.; Le Poole, I. Caroline

    2016-01-01

    We isolated gp100-reactive T cells from perilesional skin of a patient with progressive vitiligo with superior reactivity toward melanoma cells compared with tumor-infiltrating lymphocytes 1520, a melanoma-derived T-cell line reactive with the same cognate peptide. After dimer enrichment and limited

  6. Defamation on facebook: Isparta V Richter 2013 6 SA 529 (GP ...

    African Journals Online (AJOL)

    In this case discussion, a brief overview is given of the few cases already reported, but in the main the case of Isparta v Richter 2013 6 SA 4529 (GP) is discussed. In this case a South African court for the first time awarded damages to the plaintiff for defamatory comments made on Facebook. The questions that confronted ...

  7. Small-angle scattering from GP zones in Al–Cu alloy

    Indian Academy of Sciences (India)

    ... and smallangle scattering experiments were carried on the powdered samples as a function of time during artificial aging. Small-angle scattering data were analysed, and evidence has been obtained for the occurrence of spinodal decomposition as the mechanism responsible in the early stages of formation of GP zones.

  8. Speeding up IA mechanically-steered multistatic radar scheduling with GP-GPUs

    CSIR Research Space (South Africa)

    Focke, RW

    2016-07-01

    Full Text Available In this paper, the authors investigate speeding up the execution time of Interval Algebra (IA) mechanically-steered multistatic and multisite radar scheduling using a general-purpose graphical processing unit (GP-GPU). Multistatic/multisite radar...

  9. Degradation of 1,2-Dibromoethane by Mycobacterium sp. Strain GP1

    NARCIS (Netherlands)

    Poelarends, Gerrit J.; van Hylckama Vlieg, Johannes; Marchesi, Julian R.; Freitas dos Santos, Luisa M.; Janssen, Dick B.

    The newly isolated bacterial strain GP1 can utilize 1,2-dibromoethane as the sole carbon and energy source. On the basis of 16S rRNA gene sequence analysis, the organism was identified as a member of the subgroup which contains the fast-growing mycobacteria, The first step in 1,2-dibromoethane

  10. Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C. (Harvard-Med); (NIMR)

    2010-07-13

    HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

  11. The assessment of genetic risk of breast cancer : a set of GP guidelines

    NARCIS (Netherlands)

    de Bock, GH; Vlieland, TPMV; Hageman, GCHA; Oosterwijk, JC; Springer, MP; Kievit, J

    Background. Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to

  12. Antibiotics in Dutch general practice: nationwide electronic GP database and national reimbursement rates.

    NARCIS (Netherlands)

    Akkerman, A.E.; Kuyvenhoven, M.M.; Verheij, T.J.M.; Dijk, L. van

    2008-01-01

    PURPOSE: In order to assess whether different databases generate information which can be reliable compared with each other, this study aimed to assess to which degree prescribing rates for systemic antibiotics from a nationwide electronic general practitioner (GP) database correspond with national

  13. An optimized D2Q37 Lattice Boltzmann code on GP-GPUs

    NARCIS (Netherlands)

    Biferale, L.; Mantovani, F.; Pivanti, M.; Pozzati, F.; Sbragaglia, M.; Scagliarini, Andrea; Schifano, S.F.; Toschi, F.

    2013-01-01

    We describe the implementation of a thermal compressible Lattice Boltzmann algorithm on an NVIDIA Tesla C2050 system based on the Fermi GP-GPU. We consider two different versions, including and not including reactive effects. We describe the overall organization of the algorithm and give details on

  14. The bacteria binding glycoprotein salivary agglutinin (SAG/gp340) activates complement via the lectin pathway

    NARCIS (Netherlands)

    Leito, Jelani T. D.; Ligtenberg, Antoon J. M.; van Houdt, Michel; van den Berg, Timo K.; Wouters, Diana

    2011-01-01

    Salivary agglutinin (SAG), also known as gp-340 and Deleted in Malignant Brain Tumours 1, is a glycoprotein that is present in tears, lung fluid and mucosal surfaces along the gastrointestinal tract. It is encoded by the Deleted in Malignant Brain Tumours 1 gene, a member of the Scavenger Receptor

  15. Binding of radiolabeled asbestos fibers to guinea pig (gp) alveolar macrophages (AM)

    International Nuclear Information System (INIS)

    Giannotti, M.A.; Tewson, T.J.; Francsechini, M.P.; Scheule, R.K.; Holian, A.

    1990-01-01

    The mechanism by which fibrogenic particulates cause pulmonary fibrosis in humans is not understood, but is likely to involve the AM. Using two fibrogenic particulates, namely, chrysotile (CHR) and crocidolite (CRO) asbestos and gpAM as components of an in vitro model system, the authors have shown that CHR stimulates the gpAM to release superoxide anion, but CRO does not. To examine whether this difference in stimulatory abilities is a result of differences in cell-asbestos binding they have developed an efficient procedure that radiolabels asbestos fibers while retaining their bioactivity. The fibers are labeled with 68 Ge. The 68 Ge decays into 68 Ga, which then can be detected by its characteristic position emission. Both CHR and CRO asbestos were radiolabled successfully. Mild reaction conditions and short reaction times were found under which >90% of the added 68 Ge and 68 Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. A density gradient procedure was developed to quantitate the binding of asbestos to gpAM in suspension. The binding of both fibers increased with time over one hr. Thus, these results indicate that although both CHR and CRO interact with the gpAM, only CHR interacts productively to stimulate superoxide anion release

  16. Epidemiology and resistance patterns in urinary pathogens from long-term care facilities and GP populations.

    LENUS (Irish Health Repository)

    Brabazon, E D

    2012-06-01

    Urinary tract infections (UTIs) are a major source of antimicrobial prescribing in the clinical setting and a potential reservoir for the emergence of resistant organisms. Although studies have been published on resistance rates for urinary pathogens from both hospital and general practitioner (GP) settings, there is little information from Long-Term Care Facilities (LTCFs) in Ireland. This study aimed to document the epidemiology and resistance rates in urinary isolates, in the LTCF and GP setting, from samples submitted to a typical microbiology laboratory. In 2010, there were 963 urinary isolates from LTCFs and 1,169 urinary isolates from GPs, identified from patients 65 years and over, with cytology suggestive of infection. E. coil was the most common causative organism identified. There were significantly higher levels of resistance to ampicillin, co-amoxiclav, ciprofloxacin, nitrofurantoin, trimethoprim, and piperacillin\\/tazobactam in the LTCF population compared to the GP population (e.g. for E. coli, 86%-v-69%; 30%-v- 21%; 58%-v-26%, 10%-v-3%, 68%-v-48%, 10%-v- 4% respectively). Isolates with resistance mechanisms to beta-lactams, were identified in both populations. Results presented in this paper demonstrate significant differences between resistance rates in LTCF and GP populations which suggest that there are implications for empiric antimicrobial prescribing for UTIs in the LTCF setting.

  17. Extending an Afrikaans pronunciation dictionary using Dutch resources and P2P/GP2P

    CSIR Research Space (South Africa)

    Loots, L

    2010-11-01

    Full Text Available . This is compared to the more common approach of extending the Afrikaans dictionary by means of graphemeto-phoneme (G2P) conversion. The results indicate that the Afrikaans pronunciations obtained by P2P and GP2P from the Dutch dictionary are more accurate than...

  18. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

    Science.gov (United States)

    Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

    2018-02-01

    In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  20. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  1. Autographa californica multiple nucleopolyhedrovirus GP64 protein: Analysis of domain I and V amino acid interactions and membrane fusion activity

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Qianlong [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Blissard, Gary W. [Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, United State (United States); Liu, Tong-Xian [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Li, Zhaofei, E-mail: zhaofeili73@outlook.com [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China)

    2016-01-15

    The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, but no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.

  2. CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

    International Nuclear Information System (INIS)

    Sterjovski, Jasminka; Churchill, Melissa J.; Roche, Michael; Ellett, Anne; Farrugia, William; Wesselingh, Steven L.; Cunningham, Anthony L.; Ramsland, Paul A.; Gorry, Paul R.

    2011-01-01

    CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n = 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity.

  3. Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition

    NARCIS (Netherlands)

    Goudsmit, J.; Boucher, C. A.; Meloen, R. H.; Epstein, L. G.; Smit, L.; van der Hoek, L.; Bakker, M.

    1988-01-01

    PEPSCAN analysis, performed using 536 overlapping nonapeptides derived from the HTLV-III B nucleotide sequence of the region encoding the external envelope protein of 120 kDa (gp120), identified in the V3 region of gp120 a major binding site for antibodies of HIV-1-infected humans. The minimal amino

  4. Frequency and persistency of DNA vaccine encoding GP25 by oral on common carp

    Directory of Open Access Journals (Sweden)

    Sri Nuryati

    2015-05-01

    Full Text Available ABSTRACT Koi herpesvirus (KHV is a major viral pathogen that infects common carp and koi. KHV disease outbreak is happened in almost all centre of common carp culture in Indonesia and caused mass mortality. Deoxyribonucleic acid (DNA vaccination method is one of ways to cope with KHV infection. Vaccines were commonly given by injection. The aim of this research was to get frequency and persistency of DNA vaccine encoding GP25 given by oral delivery method in common carp. This research would like to determine dose, frequency of vaccination, persistency of DNA vaccine and culture medium for the bacterial host. DNA vaccine persistency test was done by using polymerase chain reaction (PCR method with the specific primer for GP25 gene. The results showed that level of DNA vaccine that could be detected in feed was 7.56 ng (equal to 1.598×1010 copies. Efficient culture medium for Escherichia coli DH5α carrying DNA vaccine was LB triptone. Feeding fish with diet supplemented with 1 mL E. coli DH5α containing DNA vaccine for each fish and two times a week allowed persistence of DNA vaccine in kindney and spleen. Keywords: common carp, KHV, DNA vaccine, GP25, persistance  ABSTRAK Koi herpesvirus (KHV adalah virus patogen utama yang menginfeksi ikan mas dan ikan koi. Wabah penyakit KHV terjadi di hampir semua sentra budidaya ikan mas di Indonesia dan menyebabkan kematian massal ikan. Metode vaksinasi DNA merupakan salah satu cara yang dapat dilakukan untuk menanggulangi serangan KHV. Pemberian vaksin umumnya dilakukan dengan cara injeksi. Tujuan penelitian ini adalah untuk menguji frekuensi dan persistensi vaksin DNA GP25 antivirus KHV yang diberikan melalui oral pada ikan mas. Pada penelitian ini dilakukan uji dosis, frekuensi pemberian vaksin, persistensi vaksin DNA, dan media kultur bakteri inang. Persistensi vaksin DNA dianalisis menggunakan metode PCR dengan primer spesifik gen GP25. Hasil penelitian menunjukkan bahwa dosis vaksin DNA yang

  5. Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHU Chen

    2014-10-01

    Full Text Available ObjectiveTo explore the early diagnostic values of serum alpha-fetoprotein (AFP, gamma-glutamyltransferase Ⅱ (GGTⅡ, and Golgi protein 73 (GP73 in patients with primary hepatocellular carcinoma (PHC. MethodsThe serum specimens of 100 patients with liver diseases (50 cases of hepatitis and liver cirrhosis and 50 cases of PHC and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic (ROC curves of single or combined test results were made, and the areas under the ROC curves (AUCs were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. ResultsThe level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups (F=16.224, P<0.05, but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group (P>0.05. Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group (F=193.128, F=20.231, P<0.05 for both. When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94.6% and the sensitivity was 98.8%. ConclusionThe GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

  6. Antiviral Activity of HIV gp120 Targeting Bispecific T Cell Engager (BiTE®) Antibody Constructs.

    Science.gov (United States)

    Brozy, Johannes; Schlaepfer, Erika; Mueller, Christina K S; Rochat, Mary-Aude; Rampini, Silvana K; Myburgh, Renier; Raum, Tobias; Kufer, Peter; Baeuerle, Patrick A; Muenz, Markus; Speck, Roberto F

    2018-05-02

    Today's gold standard in HIV therapy is the combined antiretroviral therapy (cART). It requires strict adherence by patients and life-long medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency, but cannot cure patients. The bispecific T cell engaging (BiTE®) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. We here generated BiTE® antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1+2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ϵ scFv. These engineered human BiTE® antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in PBMCs as well as in macrophages co-cultured with autologous CD8+ T-cells, the most potent being the human CD4(1+2) BiTE® antibody construct and the CD4(1+2)L17b BiTE® antibody construct. The CD4(1+2) h BiTE® antibody construct promoted HIV infection of human CD4-/CD8+ T cells. In contrast, the neutralizing B12 and the VRC01 BiTE® antibody constructs as well as the CD4(1+2)L17b BiTE® antibody construct did not. Thus, BiTE® antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential. Importance HIV is a chronic infection well controlled with the current cART. However, we lack cure of HIV, and the HIV pandemic goes on. Here we showed in vitro and ex vivo t hat a bispecific T-cell engaging (BiTE®) antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE® antibody constructs display efficient killing of gp120 expressing cells and inhibited replication in ex vivo

  7. Critical review and hydrologic application of threshold detection methods for the generalized Pareto (GP) distribution

    Science.gov (United States)

    Mamalakis, Antonios; Langousis, Andreas; Deidda, Roberto

    2016-04-01

    Estimation of extreme rainfall from data constitutes one of the most important issues in statistical hydrology, as it is associated with the design of hydraulic structures and flood water management. To that extent, based on asymptotic arguments from Extreme Excess (EE) theory, several studies have focused on developing new, or improving existing methods to fit a generalized Pareto (GP) distribution model to rainfall excesses above a properly selected threshold u. The latter is generally determined using various approaches, such as non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data, graphical methods where one studies the dependence of GP distribution parameters (or related metrics) on the threshold level u, and Goodness of Fit (GoF) metrics that, for a certain level of significance, locate the lowest threshold u that a GP distribution model is applicable. In this work, we review representative methods for GP threshold detection, discuss fundamental differences in their theoretical bases, and apply them to 1714 daily rainfall records from the NOAA-NCDC open-access database, with more than 110 years of data. We find that non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data are generally not reliable, while methods that are based on asymptotic properties of the upper distribution tail lead to unrealistically high threshold and shape parameter estimates. The latter is justified by theoretical arguments, and it is especially the case in rainfall applications, where the shape parameter of the GP distribution is low; i.e. on the order of 0.1 ÷ 0.2. Better performance is demonstrated by graphical methods and GoF metrics that rely on pre-asymptotic properties of the GP distribution. For daily rainfall, we find that GP threshold estimates range between 2÷12 mm/d with a mean value of 6.5 mm/d, while the existence of quantization in the

  8. Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family

    DEFF Research Database (Denmark)

    Silvestri, B; Calderazzo, F; Coppola, V

    1998-01-01

    We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non-specific ......We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non......-specific mitogens such as phytohaemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), was strongly reduced, probably due to the lectin-binding properties of gp90/Mac-2BP, the response to T cell receptor (TCR) agonists such as superantigens and allogeneic cells was potentiated. When...... lymphocytes were stimulated with different anti-TCR:CD3 MoAbs, both in soluble and solid-phase form, gp90/Mac-2BP was able to down-regulate the proliferative response to anti-CD3 MoAb, whereas the response to anti-TCR alphabeta MoAb was enhanced. A similar differential effect was observed when a MoAb against...

  9. Using photography to enhance GP trainees' reflective practice and professional development.

    Science.gov (United States)

    Rutherford; Forde, Emer; Priego-Hernandez, Jacqueline; Butcher, Aurelia; Wedderburn, Clare

    2018-02-08

    The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most general practitioners (GP) training programmes. Teaching through the humanities is a growing area within medical education, but one which is often considered a voluntary 'add-on' for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees' reflective capacity, self-awareness and professional development. Photography was used as a tool to develop GP trainees' skills in recognising and articulating the attitudes, feelings and values that might impact on their clinical work and to enhance their confidence in their ability to deal with these concerns/issues. We submit that photography is uniquely well suited for facilitating insight and self-reflection because it provides the ability to record 'at the touch of a button' those scenes and images to which our attention is intuitively drawn without the need for-or the interference of-conscious decisions. This allows us the opportunity to reflect later on the reasons for our intuitive attraction to these scenes. These photography workshops were a compulsory part of the GP training programme and, despite the participants' traditional scientific backgrounds, the results clearly demonstrate the willingness of participants to accept-even embrace-the use of art as a tool for learning. The GP trainees who took part in this project acknowledged it to be beneficial for both their personal and professional development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Value of combined detection of serum AFP and GP73 in early diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    GAO Haifeng

    2014-07-01

    Full Text Available ObjectiveTo investigate the value of combined detection of serum alpha-fetoprotein (AFP and Golgi protein-73 (GP73 in the diagnosis of hepatocellular carcinoma (HCC and to provide a basis for early diagnosis and differential diagnosis of HCC. MethodsA total of 408 patients hospitalized in Baoji Central Hospital from June 2012 to May 2013, as well as healthy persons who had normal test results in physical examination, were included in the study, and their specimens were collected. These patients were classified into HCC group (n=142, chronic hepatitis group (n=156, and liver cirrhosis group (n=110. Serum levels of AFP and GP73 in the three groups were measured by electrochemiluminescence immunoassay and double-antibody sandwich enzyme-linked immunosorbent assay, respectively. Comparison of test results between groups was made by analysis of variance, and comparison of rates was made by chi-square test. The sensitivity and specificity of the two indicators for the diagnosis of HCC were calculated using MedCalc statistical software. ResultsThe HCC group had significantly higher serum AFP and GP73 levels than the liver cirrhosis group and chronic hepatitis group (P<0.05; the liver cirrhosis group had significantly higher serum AFP and GP73 levels than the chronic hepatitis group (P<0.05. The sensitivity and specificity of the two indicators for the diagnosis of HCC were 95.8% and 98.6%, respectively, showing significant differences compared with those of each indicator alone (P<0.05. ConclusionCombined detection of serum AFP and GP73 has high diagnostic value and clinical significance for HCC, and they can be used as indicators for early diagnosis and differential diagnosis of HCC.

  11. Patient satisfaction with out-of-hours GP cooperatives: a longitudinal study.

    Science.gov (United States)

    Smits, Marleen; Huibers, Linda; Oude Bos, Anita; Giesen, Paul

    2012-12-01

    For over a decade, out-of-hours primary care in the Netherlands has been provided by general practitioner (GP) cooperatives. In the past years, quality improvements have been made and patients have become acquainted with the service. This may have increased patient satisfaction. The objective of this study was to examine changes in patient satisfaction with GP cooperatives over time. Longitudinal observational study. A validated patient satisfaction questionnaire was distributed in 2003-2004 (T1) and 2007-2008 (T2). Items were rated on a scale from 0 to 10 (1 = very bad; 10 = excellent). Eight GP cooperatives in the Netherlands. Stratified sample of 9600 patients. Response was 55% at T1 (n = 2634) and 51% at T2 (n = 2462). Expectations met; satisfaction with triage nurses, GPs, and organization. For most patients the care received at the GP cooperative met their expectations (T1: 86.1% and T2: 88.4%). Patients were satisfied with the triage nurses (overall grade T1: 7.73 and T2: 7.99), GPs (T1: 8.04 and T2: 8.25), and organization (overall grade T1: 7.60 and T2: 7.78). Satisfaction with triage nurses showed the largest increase over time. The quality and effectiveness of advice or treatment were given relatively low grades. Of all organizational aspects, the lowest grades were given for waiting times and information about the cooperative. In general, patients were initially satisfied with GP cooperatives and satisfaction had even increased four years later. However, there is room for improvement in the content of the advice, waiting times, and information supply. More research is needed into satisfaction of specific patient groups.

  12. Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

    Directory of Open Access Journals (Sweden)

    Long Wang

    2018-01-01

    Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

  13. Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

    Directory of Open Access Journals (Sweden)

    Cátia Teixeira

    Full Text Available HIV-1 gp41 facilitates the viral fusion through a conformational switch involving the association of three C-terminal helices along the conserved hydrophobic grooves of three N-terminal helices coiled-coil. The control of these structural rearrangements is thought to be central to HIV-1 entry and, therefore, different strategies of intervention are being developed. Herewith, we describe a procedure to simulate the folding of an HIV-1 gp41 simplified model. This procedure is based on the construction of plausible conformational pathways, which describe protein transition between non-fusogenic and fusogenic conformations. The calculation of the paths started with 100 molecular dynamics simulations of the non-fusogenic conformation, which were found to converge to different intermediate states. Those presenting defined criteria were selected for separate targeted molecular dynamics simulations, subjected to a force constant imposing a movement towards the gp41 fusogenic conformation. Despite significant diversity, a preferred sequence of events emerged when the simulations were analyzed in terms of the formation, breakage and evolution of the contacts. We pointed out 29 residues as the most relevant for the movement of gp41; also, 2696 possible interactions were reduced to only 48 major interactions, which reveals the efficiency of the method. The analysis of the evolution of the main interactions lead to the detection of four main behaviors for those contacts: stable, increasing, decreasing and repulsive interactions. Altogether, these results suggest a specific small cavity of the HIV-1 gp41 hydrophobic groove as the preferred target to small molecules.

  14. Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

    Science.gov (United States)

    Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

    2018-06-05

    Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

  15. Re-Audit of the Contents of GP Referral letters to General Adult Community Psychiatrists.

    Science.gov (United States)

    Odelola, Catherine; Jabbar, Farid

    2017-09-01

    The quality of information provided by referring general practitioners to secondary care mental health services are crucial elements in the effective management of patients. In order to establish effective communication, both primary and secondary care health professionals should contribute to planning and organising this process taking into account their different opinions and views. Anonymous questionnaire was designed to collect information on items that GPs and psychiatrist rated as most important items in GP referral letters to psychiatrists. The questionnaires were sent out electronically. Each item was scored using a rating scale where 0 was least important and 10 was most important. Items that scored 8 and above were agreed by all as the most important items. 76 GP letters were audited using a devised checklist of the identified most important items. Data was collected and analysed using a devised data collection tool. A re-audit was done 6months later. A response rate of 70% was obtained for both psychiatrists and GPs. Reasons for referral were described in almost all GP referral letters (95%). Only 24% referral letters had details about current physical health which improved to 59%. Concerns about risk were described in only 47% of letters and treatment provided by GP in 50% of letters. These improved in 79% and 71% of letters respectively in the re-audit. The involvement of professionals in devising a standardised approach for referral letters has improved communication in this re-audit between GPs and Psychiatrists. This is evident in the improvement in key aspects of the referral letters: past medical history, past psychiatric history, current physical health, treatment provided by GP. Efficient communication between GPs and psychiatrists improves the quality of health care for patients.

  16. 77 FR 70826 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Uniform...

    Science.gov (United States)

    2012-11-27

    ... for OMB Review; Comment Request; Uniform Billing Form ACTION: Notice. SUMMARY: The Department of Labor... collection request (ICR) revision titled, ``Uniform Billing Form,'' (Form OWCP-04) to the Office of.... In addition, notwithstanding any other provisions of law, no person shall generally be subject to...

  17. 75 FR 79052 - Proposed Collection; Request for Comments on a Revised Information Collection: (OMB Control No...

    Science.gov (United States)

    2010-12-17

    ... Civil Service or Federal Employees retirement, Federal or Retired Federal Employees Health Benefits requests to enroll or change enrollment, or Federal Employees' Group Life Insurance coverage. This form...

  18. A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses

    International Nuclear Information System (INIS)

    Katou, Yasuhiro; Yamada, Hayato; Ikeda, Motoko; Kobayashi, Michihiro

    2010-01-01

    We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinant AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results indicate that Ac-GP64 H155 facilitates the low-pH-triggered membrane fusion reaction between virus envelopes and endosomal membranes.

  19. 77 FR 75971 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2012-12-26

    ... Ecosystems for Recreation/Tourism. OMB Control Number: None. Form Number(s): NA. Type of Request: Regular... all ecosystem services for the Guanica Bay Watershed and for recreation-tourism for all of Puerto Rico...

  20. 77 FR 50986 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2012-08-23

    ...: National Oceanic and Atmospheric Administration (NOAA). Title: Coastal Zone Management Program Administration. OMB Control Number: 0648-0119. Form Number(s): NA. Type of Request: Regular submission (revision...; [[Page 50987