Sample records for components thereof dn

  1. 76 FR 66750 - Certain Automotive GPS Navigation Systems, Components Thereof, and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-27

    ... INTERNATIONAL TRADE COMMISSION [DN 2850] Certain Automotive GPS Navigation Systems, Components... given that the U.S. International Trade Commission has received a complaint entitled In Re Certain Automotive GPS Navigation Systems, Components Thereof, And Products Containing Same, DN 2850; the Commission...

  2. 78 FR 17940 - Certain Computerized Orthopedic Surgical Devices, Software, Implants, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-25

    ..., Software, Implants, and Components Thereof; Notice of Receipt of Complaint; Solicitation of Comments... Certain Computerized Orthopedic Surgical Devices, Software, Implants, and Components Thereof, DN 2945; the... importation of certain computerized orthopedic surgical devices, software, implants, and components thereof...

  3. 77 FR 4059 - Certain Electronic Devices for Capturing and Transmitting Images, and Components Thereof; Receipt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... Images, and Components Thereof; Receipt of Complaint; Solicitation of Comments Relating to the Public... Devices for Capturing and Transmitting Images, and Components Thereof, DN 2869; the Commission is... importation of certain electronic devices for capturing and transmitting images, and components thereof. The...

  4. 78 FR 32689 - Certain Portable Electronic Communications Devices, Including Mobile Phones and Components...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ..., Including Mobile Phones and Components Thereof Notice of Receipt of Complaint; Solicitation of Comments... Certain Portable Electronic Communications Devices, Including Mobile Phones and Components Thereof, DN... mobile phones and components thereof. The complaint names as respondents HTC Corporation of China and HTC...

  5. 78 FR 36572 - Certain Crawler Cranes and Components Thereof Notice of Receipt of Complaint; Solicitation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... INTERNATIONAL TRADE COMMISSION [Docket No. 2960] Certain Crawler Cranes and Components Thereof... Trade Commission has received a complaint entitled Certain Crawler Cranes and Components Thereof, DN...) of the Commission's Rules of Practice and Procedure filed on behalf of Manitowoc Cranes, LLC on June...

  6. 77 FR 20417 - Certain Cameras and Mobile Devices, Related Software and Firmware, and Components Thereof and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... INTERNATIONAL TRADE COMMISSION [DN 2891] Certain Cameras and Mobile Devices, Related Software and... complaint entitled Certain Cameras and Mobile Devices, Related Software and Firmware, and Components Thereof... cameras and mobile devices, related software and firmware, and components thereof and products containing...

  7. 77 FR 5275 - Certain Ink Application Devices and Components Thereof and Methods of Using the Same; Receipt of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... INTERNATIONAL TRADE COMMISSION [DN 2874] Certain Ink Application Devices and Components Thereof... the U.S. International Trade Commission has received a complaint entitled In Re Certain Ink... United States after importation of certain ink application devices and components thereof and methods of...

  8. 75 FR 82410 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-30

    ... Certain Game Devices, Components Thereof, and Products Containing the Same, DN 2776; the Commission is... United States after importation of certain game devices, components thereof, and products containing the...

  9. 76 FR 34100 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ... Certain GPS Navigation Products, Components Thereof, and Related Software, DN 2814; the Commission is... importation of certain GPS navigation products, components thereof, and related software. The complaint names...

  10. 76 FR 54251 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-31

    ... Certain Digital Photo Frames and Image Display Devices and Components Thereof, DN 2842; the Commission is... importation of certain digital photo frames and image display devices and components thereof. The complaint...

  11. 76 FR 66750 - Certain Projectors With Controlled-Angle Optical Retarders, Components Thereof, and Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-27

    ... INTERNATIONAL TRADE COMMISSION [DN 2849] Certain Projectors With Controlled-Angle Optical... Re Certain Projectors with Controlled-Angle Optical Retarders, Components Thereof, And Products... complaint. FOR FURTHER INFORMATION CONTACT: James R. Holbein, Secretary to the Commission, U.S...

  12. 76 FR 25706 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ... Certain Electronic Devices Having a Digital Television Receiver and Components Thereof, DN 2801; the... importation of certain electronic devices having a digital television receiver and components thereof. The... health and welfare in the United States, competitive conditions in the United States economy, the...

  13. 75 FR 62140 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-07

    ... Certain Mobile Devices, Associated Software, and Components Thereof, DN 2757; the Commission is soliciting... into the United States, the sale for importation, and the sale within the United States after importation of certain mobile devices, associated software, and components thereof. The complaint names as...

  14. 76 FR 7583 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-10

    ... Certain Digital Televisions and Components Thereof, DN 2785; the Commission is soliciting comments on any... digital televisions and components thereof. The complaint names as respondents Sony Corporation of Tokyo... in the United States economy, the production of like or directly competitive articles in the United...

  15. 75 FR 57500 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-21

    ... Certain Digital Televisions and Components Thereof, DN 2755 ; the Commission is soliciting comments on any... digital televisions and components thereof. The complaint names as respondents Vizio, Inc. of Irvine, CA... States, competitive conditions in the United States economy, the production of like or directly...

  16. 76 FR 62842 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-11

    ... Certain Integrated Solar Systems and Components Thereof, DN 2847; the Commission is soliciting comments on... importation of certain integrated solar systems and components thereof. The complaint names as respondents Zep... Commission has received a complaint filed on behalf of Westinghouse Solar, Inc. on October 4, 2011. The...

  17. 77 FR 17093 - Certain Food Waste Disposers and Components and Packaging Thereof: Notice of Receipt of Complaint...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-23

    ... INTERNATIONAL TRADE COMMISSION [DN 2886] Certain Food Waste Disposers and Components and Packaging...: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has received a complaint entitled Certain Food Waste Disposers and Components and...

  18. 77 FR 14423 - Certain Food Containers, Cups, Plates, Cutlery, and Related Items, and Packaging Thereof; Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... INTERNATIONAL TRADE COMMISSION [DN 2883] Certain Food Containers, Cups, Plates, Cutlery, and... Containers, Cups, Plates, Cutlery, and Related Items, and Packaging Thereof, DN 2883; the Commission is... importation of certain food containers, cups, plates, cutlery, and related items, and packaging thereof. The...

  19. 78 FR 59370 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-26

    ... Certain Marine Sonar Imaging Devices, Products Containing the Same, and Components Thereof, DN 2981; the... United States after importation of certain marine sonar imaging devices, products containing the same...

  20. 76 FR 18247 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... Certain Video Game Systems and Wireless Controller and Components Thereof, DN 2791; the Commission is... sale within the United States after importation of certain video game systems and wireless controller...

  1. 76 FR 45615 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... Certain Wireless Devices with 3G Capabilities and Components Thereof, DN 2835; the Commission is... importation, and the sale within the United States after importation of certain wireless devices with 3g...

  2. 76 FR 36935 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-23

    ... Certain Digital Televisions and Components Thereof, DN 2819; the Commission is soliciting comments on any... for importation, and the sale within the United States after importation of certain digital... Westinghouse Digital, LLC, Orange County, CA. The complainant, proposed respondents, other interested parties...

  3. 77 FR 6142 - Certain Ink Application Devices and Components Thereof and Methods of Using the Same (Corrected...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-07

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. DN 2874] Certain Ink Application Devices and... Comments Relating to the Public Interest AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has received a complaint...

  4. 75 FR 72838 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-26

    ... Certain Gaming and Entertainment Consoles, Related Software, and Components Thereof, DN 2770; the... E Street, SW., Washington, DC 20436, telephone (202) 205-2000. The public version of the complaint... Secretary, U.S. International Trade Commission, 500 E Street, SW., Washington, DC 20436, telephone (202) 205...

  5. 76 FR 40744 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... entitled In Re Electronic Digital Media Devices and Components Thereof, DN 2827; the Commission is soliciting comments on any public interest issues raised by the complaint. FOR FURTHER INFORMATION CONTACT... Commission, 500 E Street, SW., Washington, DC 20436, telephone (202) 205-2000. General information concerning...

  6. 76 FR 51395 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... Certain Digital Televisions Containing Integrated Circuit Devices and Components Thereof, DN 2840; the... accessed on the Commission's electronic docket (EDIS) at http://edis.usitc.gov , and will be available for....gov ). The public record for this investigation may be viewed on the Commission's electronic docket...

  7. 78 FR 958 - Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof Notice of Receipt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ... INTERNATIONAL TRADE COMMISSION [DN 2929] Certain Wireless Devices With 3G and/or 4G Capabilities... Interest AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has received a complaint entitled Certain Wireless Devices...

  8. 78 FR 79480 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ...Notice is hereby given that the U.S. International Trade Commission has received a complaint entitled Certain Vision-Based Driver Assistance System Cameras and Components Thereof, DN 2993; the Commission is soliciting comments on any public interest issues raised by the complaint or complainant's filing under section 210.8(b) of the Commission's Rules of Practice and Procedure (19 CFR 210.8(b)).

  9. 75 FR 76753 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-09

    ... Certain Handbags, Luggage, Accessories and Packaging Thereof, DN 2772; the Commission is soliciting... within the United States after importation of certain handbags, luggage, accessories and packaging...

  10. Development of a face-to-face injunctive norms brief motivational intervention for college drinkers and preliminary outcomes

    PubMed Central

    Prince, Mark A.; Maisto, Stephen A.; Rice, Samara L.; Carey, Kate B.

    2015-01-01

    Findings are presented from the first randomized clinical trial that compared changes in alcohol consumption and alcohol-related consequences among college student drinkers from baseline to follow-up across four conditions: (a) a new single component injunctive norms brief motivational intervention (IN-BMI) condition, (b) a single component descriptive norms brief motivational intervention (DN-BMI), (c) a Combined IN and DN brief motivational intervention (Combined-BMI), and (d) assessment-only control. DN-BMI focused on the juxtaposition of personal, perceived, and actual alcohol use by typical same-sex students at your university. INBMI focused on the juxtaposition of personal, perceived, and actual attitudes about alcohol related consequences by the typical same-sex student at your university. Exploratory analyses assessed the effect of IN-BMI and DN-BMI on matched (e.g., the effect of DN-BMI on perceived DN) and mismatched norms (e.g., the effect of DN-BMI on perceived IN). IN-BMI resulted in greater decreases in alcohol use and consequences when delivered alone and in conjunction with DN-BMI compared to the control condition. Further, the Combined-BMI condition reported greater reductions in alcohol use but not consequences compared to the DN condition. Receiving IN-BMI either alone or in combination with DN-BMI produced greater changes in IN perceptions than were produced in the control group. Grounded in norms theory, this study examined how college student problem drinking is affected by both IN-BMI and DN-BMI alone and in combination. We conclude that IN-BMI alone or in combination with DN-BMI is able to modify alcohol use and reduce alcohol related consequences. PMID:26478943

  11. 75 FR 34482 - Certain Biometric Scanning Devices, Components Thereof, Associated Software, and Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ..., Components Thereof, Associated Software, and Products Containing the Same; Notice of Investigation AGENCY: U... scanning devices, components thereof, associated software, and products containing the same by reason of... after importation of certain biometric scanning devices, components thereof, associated software, or...

  12. 76 FR 70164 - Certain Devices With Secure Communication Capabilities, Components Thereof, and Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ... capabilities, components thereof, and products containing the same. The complaint names Apple Inc. of Cupertino..., Components Thereof, and Products Containing the Same; Receipt of Complaint; Solicitation of Comments Relating... Certain Devices with Secure Communication Capabilities, Components Thereof, and Products Containing the...

  13. 78 FR 14357 - Certain Compact Fluorescent Reflector Lamps, Products Containing Same and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ... Reflector Lamps, Products Containing Same and Components Thereof; Institution of Investigation AGENCY: U.S... fluorescent reflector lamps, products containing same and components thereof by reason of infringement of... compact fluorescent reflector lamps, products containing same and components thereof by reason of...

  14. 75 FR 8399 - In the Matter of Certain Mobile Communications and Computer Devices and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... Communications and Computer Devices and Components Thereof; Notice of Investigation AGENCY: U.S. International... States after importation of certain mobile communications and computer devices and components thereof by... importation of certain mobile communications or computer devices or components thereof that infringe one or...

  15. 76 FR 39896 - In the Matter of Certain GPS Navigation Products, Components Thereof, and Related Software...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... Products, Components Thereof, and Related Software; Notice of Institution of Investigation; Institution of... importation of certain GPS navigation products, components thereof, and related software by reason of... importation of certain GPS navigation products, components thereof, and related software that infringe one or...

  16. 77 FR 35427 - Certain Mobile Devices, Associated Software, and Components Thereof Final Determination of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... Software, and Components Thereof Final Determination of Violation; Issuance of a Limited Exclusion Order... importation of certain mobile devices, associated software, and components thereof by reason of infringement... importation of certain mobile devices, associated software, and components thereof containing same by reason...

  17. 77 FR 51572 - Certain Wireless Consumer Electronics Devices and Components Thereof; Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-24

    ... Electronics Devices and Components Thereof; Institution of Investigation Pursuant to 19 U.S.C. 1337 AGENCY: U... importation of certain wireless consumer electronics devices and components thereof by reason of infringement... wireless consumer electronics devices and components thereof that infringe one or more of claims 1, 6, 7, 9...

  18. 76 FR 11511 - In the Matter of Certain Set-Top Boxes, and Hardware and Software Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... Hardware and Software Components Thereof; Notice of Investigation AGENCY: U.S. International Trade... boxes, and hardware and software components thereof by reason of infringement of certain claims of U.S... after importation of certain set-top boxes, and hardware and software components thereof that infringe...

  19. 77 FR 34063 - Certain Electronic Devices, Including Mobile Phones and Tablet Computers, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-08

    ... Phones and Tablet Computers, and Components Thereof Institution of Investigation AGENCY: U.S... computers, and components thereof by reason of infringement of certain claims of U.S. Patent No. 5,570,369... mobile phones and tablet computers, and components thereof that infringe one or more of claims 1-3 and 5...

  20. 75 FR 68379 - In the Matter of: Certain Mobile Devices, Associated Software, and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ..., Associated Software, and Components Thereof; Notice of Investigation AGENCY: U.S. International Trade..., associated software, and components thereof by reason of infringement of certain claims of U.S. Patent No. 5..., associated software, and components thereof that infringe one or more of claims 1-4, 22, 26, 31, and 36 of...

  1. 77 FR 26041 - Certain Cameras and Mobile Devices, Related Software and Firmware, and Components Thereof and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ... Software and Firmware, and Components Thereof and Products Containing the Same; Institution of..., related software and firmware, and components thereof and products containing the same by reason of... after importation of certain cameras and mobile devices, related software and firmware, and components...

  2. 75 FR 20861 - Certain Digital Set-Top Boxes and Components Thereof; Notice of Investigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-712] Certain Digital Set-Top Boxes and Components... the United States after importation of certain digital set-top boxes and components thereof that... after importation of certain digital set- top boxes and components thereof that infringe one or more of...

  3. 75 FR 80843 - In the Matter of Certain Gaming and Entertainment Consoles, Related Software, and Components...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-23

    ... Entertainment Consoles, Related Software, and Components Thereof; Notice of Investigation AGENCY: U.S..., related software, and components thereof by reason of infringement of certain claims of U.S. Patent No. 5... gaming and entertainment consoles, related software, and components thereof that infringe one or more of...

  4. 76 FR 59737 - In the Matter of Certain Digital Photo Frames and Image Display Devices and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-27

    ... Frames and Image Display Devices and Components Thereof; Notice of Institution of Investigation... United States after importation of certain digital photo frames and image display devices and components... certain digital photo frames and image display devices and components thereof that infringe one or more of...

  5. 77 FR 32996 - Certain Handheld Electronic Computing Devices, Related Software, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-04

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-769] Certain Handheld Electronic Computing Devices, Related Software, and Components Thereof; Termination of the Investigation Based on... electronic computing devices, related software, and components thereof by reason of infringement of certain...

  6. 76 FR 54252 - In the Matter of Certain Wireless Devices With 3G Capabilities and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-31

    ... With 3G Capabilities and Components Thereof; Notice of Institution of Investigation Institution of... States after importation of certain wireless devices with 3G capabilities and components thereof by... after [[Page 54253

  7. 77 FR 16562 - Certain Navigation Products, Components Thereof, and Related Software; Determination Not To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-21

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-810] Certain Navigation Products, Components Thereof, and Related Software; Determination Not To Review an Initial Determination Granting a... United States after importation of certain navigation products, components thereof, and related software...

  8. 78 FR 52563 - Certain Sleep-Disordered Breathing Treatment Systems and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-890] Certain Sleep-Disordered Breathing... certain sleep- disordered breathing treatment systems and components thereof by reason of infringement of... after importation of certain sleep- disordered breathing treatment systems and components thereof that...

  9. 77 FR 13350 - Certain Automotive GPS Navigation Systems, Components Thereof, and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-06

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-814] Certain Automotive GPS Navigation Systems, Components Thereof, and Products Containing Same; Determination Not To Review Initial... importation of certain automotive GPS navigation systems, components thereof, and products containing the same...

  10. 78 FR 16531 - Certain Electronic Devices for Capturing and Transmitting Images, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-831] Certain Electronic Devices for Capturing and Transmitting Images, and Components Thereof; Commission Determination Not To Review an Initial... certain electronic devices for capturing and transmitting images, and components thereof. The complaint...

  11. 76 FR 22918 - In the Matter of Certain Handheld Electronic Computing Devices, Related Software, and Components...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... Computing Devices, Related Software, and Components Thereof; Notice of Investigation AGENCY: U.S... devices, related software, and components thereof by reason of infringement of certain claims of U.S... devices, related software, and components thereof that infringe one or more of claims 1 and 5 of the '372...

  12. 77 FR 24738 - Certain Wireless Communication Devices and Systems, Components Thereof, and Products Containing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... Devices and Systems, Components Thereof, and Products Containing Same; Notice of Commission Determination... certain wireless communication devices and systems, components thereof, and products containing the same..., California; Apple Inc. of Cupertino, California; Aruba Networks, Inc. of Sunnyvale, California; Meru Networks...

  13. 76 FR 69285 - Certain Game Devices, Components Thereof, and Products Containing the Same; Determination Not To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-08

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-757] Certain Game Devices, Components Thereof, and Products Containing the Same; Determination Not To Review An Initial Determination Granting... the United States after importation of certain game devices, components thereof, and products...

  14. 75 FR 43205 - Enforcement Proceeding: In the Matter of: Certain Voltage Regulators, Components Thereof and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-564] Enforcement Proceeding: In the Matter of: Certain Voltage Regulators, Components Thereof and Products Containing Same; Notice of Final Determination... the United States after importation of certain voltage regulators, components thereof and products...

  15. 78 FR 19311 - Certain Radio Frequency Identification (“RFID”) Products And Components Thereof; Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-29

    ... Identification (``RFID'') Products And Components Thereof; Institution of Investigation Pursuant to 19 U.S.C... sale within the United States after importation of certain radio frequency identification (``RFID... after importation of certain radio frequency identification (``RFID'') products and components thereof...

  16. 77 FR 26041 - Certain Computers and Computer Peripheral Devices and Components Thereof and Products Containing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-841] Certain Computers and Computer Peripheral... after importation of certain computers and computer peripheral devices and components thereof and... computers and computer peripheral devices and components thereof and products containing the same that...

  17. 77 FR 58577 - Certain Video Game Systems and Wireless Controllers and Components Thereof; Notice of Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-21

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-770] Certain Video Game Systems and Wireless Controllers and Components Thereof; Notice of Request for Statements on the Public Interest AGENCY... desist order against certain video game systems and wireless controllers and components thereof, imported...

  18. 78 FR 68091 - Certain Marine Sonar Imaging Devices, Products Containing the Same, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-898] Certain Marine Sonar Imaging Devices... importation of certain marine sonar imaging devices, products containing the same, and components thereof by... marine sonar imaging devices, products containing the same, and components thereof by reason of...

  19. 77 FR 27078 - Certain Electronic Devices, Including Mobile Phones and Tablet Computers, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-08

    ... Phones and Tablet Computers, and Components Thereof; Notice of Receipt of Complaint; Solicitation of... entitled Certain Electronic Devices, Including Mobile Phones and Tablet Computers, and Components Thereof... the United States after importation of certain electronic devices, including mobile phones and tablet...

  20. 76 FR 12994 - In the Matter of Certain Digital Televisions and Components Thereof, and Certain Electronic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-09

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-764] In the Matter of Certain Digital Televisions and Components Thereof, and Certain Electronic Devices Having a Blu-Ray Disc Player and Components Thereof; Notice of Investigation AGENCY: U.S. International Trade Commission. ACTION: Institution of...

  1. 76 FR 69284 - Certain Integrated Solar Power Systems and Components Thereof: Notice of Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-08

    ... the United States after importation of certain integrated solar power systems and components thereof... certain integrated solar power systems and components thereof that infringe one or more of claims 6 and 10... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-811] Certain Integrated Solar Power...

  2. 77 FR 39736 - Certain Integrated Solar Power Systems and Components Thereof; Notice of Termination of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ... certain integrated solar power systems and components thereof by reason of infringement of certain claims... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-811] Certain Integrated Solar Power Systems and Components Thereof; Notice of Termination of the Investigation Based on Settlement AGENCY: U.S...

  3. 77 FR 22611 - Certain Set-Top Boxes, and Hardware and Software Components Thereof; Determination Not To Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-761] Certain Set-Top Boxes, and Hardware and Software Components Thereof; Determination Not To Review Initial Determination Terminating... certain set-top boxes, and hardware and software components thereof by reason of infringement of various...

  4. 77 FR 16860 - Certain GPS Navigation Products, Components Thereof, and Related Software; Termination of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-22

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-783] Certain GPS Navigation Products, Components Thereof, and Related Software; Termination of Investigation on the Basis of Settlement AGENCY: U.S... GPS navigation products, components thereof, and related software, by reason of the infringement of...

  5. 76 FR 39895 - In the Matter of Certain Microprocessors, Components Thereof, and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-781] In the Matter of Certain Microprocessors... importation of certain microprocessors, components thereof, and products containing same by reason of... microprocessors, components thereof, and products containing same that infringe one or more of claims 11-16, 41...

  6. 76 FR 55944 - In the Matter of Certain Electronic Devices With Image Processing Systems, Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... With Image Processing Systems, Components Thereof, and Associated Software; Notice of Commission... importation of certain electronic devices with image processing systems, components thereof, and associated... direct infringement is asserted and the accused article does not meet every limitation of the asserted...

  7. 75 FR 65656 - In the Matter of: Certain Notebook Computer Products and Components Thereof; Notice of Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-26

    ... States after importation of certain notebook computer products and components thereof by reason of... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-705] In the Matter of: Certain Notebook Computer Products and Components Thereof; Notice of Commission Determination Not To Review an Initial...

  8. 78 FR 55294 - Certain Wireless Devices With 3G Capabilities and Components Thereof Commission Determination To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-10

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-800] Certain Wireless Devices With 3G Capabilities and Components Thereof Commission Determination To Review the Final Initial Determination Finding... importation of certain wireless devices with 3G capabilities and components thereof by reason of infringement...

  9. Hidden targets of ubiquitin proteasome system: To prevent diabetic nephropathy.

    PubMed

    Goru, Santosh Kumar; Kadakol, Almesh; Gaikwad, Anil Bhanudas

    2017-06-01

    Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes. UPS mainly involves in protein homeostatis through ubiquitination (post translational modification) and proteasomal degradation of various proteins. Ubiquitination, not only involves in proteasomal degradation, but also directs the substrate proteins to participate in multitude of cell signalling pathways. However, very little is known about ubiquitination and UPS in the progression of DN. This review mainly focuses on UPS and its components including E2 conjugating enzymes, E3 ligases and deubiquitinases (DUBs) in the development of DN and thus may help us to find novel therapeutic targets with in UPS to prevent DN completely in future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 75 FR 36677 - In the Matter of Certain Inkjet Ink Cartridges With Printheads and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-711] In the Matter of Certain Inkjet Ink Cartridges With Printheads and Components Thereof; Notice of a Commission Determination Not To Review an... importation of certain inkjet ink cartridges with printheads and components thereof by reason of infringement...

  11. 76 FR 51055 - In the Matter of Certain Inkjet Ink Cartridges with Printheads and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-723] In the Matter of Certain Inkjet Ink... importation of certain inkjet ink cartridges with printheads and components thereof by reason of infringement... importation of the accused inkjet ink cartridges with printheads and components thereof. Regarding...

  12. 78 FR 56245 - Certain Wireless Consumer Electronics Devices and Components Thereof; Notice of Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-12

    ... Electronics Devices and Components Thereof; Notice of Request for Statements on the Public Interest AGENCY: U... wireless consumer electronics devices and components thereof imported by respondents Acer, Inc. of Taipei... Communications, Inc. of San Diego, California; LG Electronics, Inc. of Seoul, Korea; LG Electronics U.S.A., Inc...

  13. 76 FR 41523 - In the Matter of Certain Mobile Communications and Computer Devices and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... Communications and Computer Devices and Components Thereof; Notice of Commission Determination Not To Review an... in its entirety Inv. No. 337-TA-704, Certain Mobile Communications and Computer Devices and... importation of certain mobile communications and computer devices and components thereof by reason of...

  14. 76 FR 5206 - In the Matter of Certain Game Devices, Components Thereof, and Products Containing the Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-28

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-757] In the Matter of Certain Game Devices... importation of certain game devices, components thereof, and products containing the same by reason of... certain game devices, components thereof, and products containing the same that infringe one or more of...

  15. 76 FR 68504 - Advisory Opinion Proceeding; Certain Coaxial Cable Connectors and Components Thereof and Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... Coaxial Cable Connectors and Components Thereof and Products Containing Same; Determination To Institute... coaxial cable connectors and components thereof and products containing the same by reason of infringement... under Commission Rule 210.79 (19 CFR 210.79) that would declare that its coaxial cable connectors...

  16. 77 FR 14043 - Certain Mobile Devices, Associated Software, and Components Thereof; Determination To Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-08

    ... Software, and Components Thereof; Determination To Review Final Initial Determination AGENCY: U.S..., and the sale within the United States after importation of certain mobile devices, associated software... software, and components thereof containing same by reason of infringement of one or more of claims 1, 2, 5...

  17. 75 FR 38118 - In the Matter of Certain Electronic Devices With Image Processing Systems, Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... With Image Processing Systems, Components Thereof, and Associated Software; Notice of Investigation..., and associated software by reason of infringement of certain claims of U.S. Patent Nos. 7,043,087... processing systems, components thereof, and associated software that infringe one or more of claims 1, 6, and...

  18. 75 FR 47027 - In the Matter of: Certain Devices Having Elastomeric Gel and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... Elastomeric Gel and Components Thereof; Notice of Investigation AGENCY: U.S. International Trade Commission... importation, and the sale within the United States after importation of certain devices having elastomeric gel... after importation of certain devices having elastomeric gel and components thereof that infringe one or...

  19. 75 FR 17437 - In the Matter of Certain Notebook Computer Products and Components Thereof; Notice of Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... importation of certain notebook computer products and components thereof by reason of infringement of the '693... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-705] In the Matter of Certain Notebook Computer Products and Components Thereof; Notice of Commission Decision Not To Review an Initial...

  20. 75 FR 8400 - In the Matter of Certain Notebook Computer Products and Components Thereof; Notice of Investigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-705] In the Matter of Certain Notebook Computer... United States after importation of certain notebook computer products and components thereof by reason of... after importation of certain notebook computer products or components thereof that infringe one or more...

  1. 77 FR 26788 - Certain Wireless Devices With 3G Capabilities and Components Thereof Determination Not To Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-800] Certain Wireless Devices With 3G Capabilities and Components Thereof Determination Not To Review Initial Determination To Amend the Notice of... importation of certain wireless devices with 3G capabilities and components thereof by reason of infringement...

  2. System and method for detecting cells or components thereof

    DOEpatents

    Porter, Marc D [Ames, IA; Lipert, Robert J [Ames, IA; Doyle, Robert T [Ames, IA; Grubisha, Desiree S [Corona, CA; Rahman, Salma [Ames, IA

    2009-01-06

    A system and method for detecting a detectably labeled cell or component thereof in a sample comprising one or more cells or components thereof, at least one cell or component thereof of which is detectably labeled with at least two detectable labels. In one embodiment, the method comprises: (i) introducing the sample into one or more flow cells of a flow cytometer, (ii) irradiating the sample with one or more light sources that are absorbed by the at least two detectable labels, the absorption of which is to be detected, and (iii) detecting simultaneously the absorption of light by the at least two detectable labels on the detectably labeled cell or component thereof with an array of photomultiplier tubes, which are operably linked to two or more filters that selectively transmit detectable emissions from the at least two detectable labels.

  3. MONO-(3-CARBOXYPROPYL) PHTHALATE, A METABOLITE OF DI-N-OCTYL PHTHALATE

    EPA Science Inventory

    Di-n-octyl phthalate (DnOP) is found as a component of mixed C6–C10 linear-chain phthalates used as plasticizers in various polyvinyl chloride applications, including flooring and carpet tiles. Following exposure and absorption, DnOP is metabolized to its hydrolytic monoester, mo...

  4. 75 FR 60480 - In the Matter of Certain Bulk Welding Wire Containers and Components Thereof and Welding Wire...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-30

    ... Welding Wire Containers and Components Thereof and Welding Wire; Notice of Commission Determination To... within the United States after importation of certain bulk welding wire containers, components thereof, and welding wire by reason of infringement of certain claims of United States Patent Nos. 6,260,781; 6...

  5. 76 FR 68209 - Certain Navigation Products, Components Thereof, and Related Software; Institution of Investigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ..., Components Thereof, and Related Software; Institution of Investigation AGENCY: U.S. International Trade... navigation products, components thereof, and related software by reason of infringement of certain claims of... related software that infringe one or more of claims 1, 2, 11, and 16 of the '565 patent; claim 1 of the...

  6. 78 FR 16707 - Certain Digital Photo Frames and Image Display Devices and Components Thereof; Issuance of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-18

    ... Image Display Devices and Components Thereof; Issuance of a Limited Exclusion Order and Cease and Desist... within the United States after importation of certain digital photo frames and image display devices and...: (1) The unlicensed entry of digital photo frames and image display devices and components thereof...

  7. [Effects of flavonoids from Pyrrosiae folium on pathological changes and inflammatory response of diabetic nephropathy].

    PubMed

    Liu, Xu-Lin; Liu, Wen-Ping; Wang, Li-Li; Feng, Liang

    2018-06-01

    Diabetic nephropathy (DN) is closely related to immune-mediated inflammatory damage. Pyrrosiae folium is used commonly for the urinary system diseases with a good efficacy, which contains abundant flavonoids (SWHT). This study was performed to investigate the therapeutic effect of SWHT on DN and its effect on inflammatory response. In this study, the main active components of SWHT were identified by high performance liquid chromatography (HPLC). The results showed that SWHT mainly contained mangiferin and isomucoside. Rat model of diabetic nephropathy (DN) was established by feeding high glucose & high fat diet and injecting streptozocin (STZ). Then the rats were randomly divided into control group, DN model group, positive control group, and SWHT groups (50, 100, 200 mg·kg⁻¹, ig). The levels of AGEs and RAGE in serum were measured by ELISA after 12 weeks of drug administration. The serum creatinine, blood urea nitrogen and total protein levels were detected by using test kit. HE staining and transmission electron microscopy were applied to observe the pathological changes and structure of renal tissue. Western blot and ELISA were used to detect the protein expression and content levels of interleukin 6 (IL-6), tumor necrosis factor (TNF-α) and IL-1β in renal tissue. Results showed that SWHT significantly decreased serum AGEs and RAGE levels in DN rats; decreased serum creatinine, blood urea nitrogen and total urinary protein levels, improved renal pathological damages and reduced basement membrane thickening in DN rats. In addition, SWHT down-regulated the protein expression levels of inflammatory mediators IL-6, TNF-α and IL-1β. The research studies indicated that SWHT component had a potential anti-diabetic nephropathy activity, and its improvement effect on pathological damages may be related to reducing inflammation. This provides the basis for the scientific and rational application of P. folium, and also provides active components for further development of Chinese medicine for diabetic nephropathy. Copyright© by the Chinese Pharmaceutical Association.

  8. Metabolomics study of cadmium-induced diabetic nephropathy and protective effect of caffeic acid phenethyl ester using UPLC-Q-TOF-MS combined with pattern recognition.

    PubMed

    Gong, Pin; Chang, Xiangna; Chen, Xuefeng; Bai, Xiaohuan; Wen, He; Pi, Sihui; Yang, Wenjuan; Wang, Lan; Chen, Fuxin

    2017-09-01

    Diabetic nephropathy (DN) is the most severe complication of diabetes and multiple factors are involved in the pathogenesis of DN. Among them, cadmium (Cd) acts as a risk factor inducing the occurrence of DN. The present study focused on investigating the protective role of caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, against Cd-induced DN in mice based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS)and pattern recognition. Serum and urine biochemical indexes were detected and histopathological observation has been done to evaluate the damage of Cd on animals. Moreover, the global serum profiles of different groups were distinguished by UPLC-Q-TOF-MS and principal component analysis (PCA) were applied for group differentiation and marker selection. Moreover, the influence of Cd on the oxidative status in DN mice were also evaluated by assessing the parameters of oxidative stress, proinflammatory cytokines and antioxidant competence. As shown in the scores plots, the distinct clustering among controls, DN and CAPE groups were observed, significant changes in serum levels of LysoPC(18:1(11Z)), 2,3-dinor-8-iso-PGF2a, PS(18:1(9Z)/18:1(9Z)), DG(17:0/22:4 (7Z,10Z, 13Z, 16Z)/0:0) and Arachidonic acid(AA) were noted and identified as potential biomarkers, the effect of CAPE reverted them back to near normalcy. Further, It was observed a significant improvement in lipid peroxides (LPO) and protein carbonyls (PCO) levels in Cd-induced DN kidneys along with a significant decline in superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels, however, CAPE relieved these changes. In conclusion, the study suggested that the pathogenesis of DN caused by Cd probably owes to the perturbations of lipid metabolism and AA metabolism; CAPE seems to be effective agent and may be related to its potent antioxidant, anti-inflammatory properties and action as an Nrf2 activator. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Change in Biotypic Diversity of Russian Wheat Aphid (Hemiptera: Aphididae) Populations in the United States.

    PubMed

    Puterka, G J; Giles, K L; Brown, M J; Nicholson, S J; Hammon, R W; Peairs, F B; Randolph, T L; Michaels, G J; Bynum, E D; Springer, T L; Armstrong, J S; Mornhinweg, D W

    2015-04-01

    A key component of Russian wheat aphid, Diuraphis noxia (Kurdjumov), management has been through planting resistant wheat cultivars. A new biotype, RWA2, appeared in 2003 which caused widespread damage to wheat cultivars containing the Dn4 gene. Biotypic diversity in Russian wheat aphid populations has not been addressed since 2005 when RWA2 dominated the biotype complex. Our objectives were to determine the biotypic diversity in the Central Great Plains and Colorado Plateau at regional (2010, 2011, 2013) and local (2012) levels and detect the presence of new Russian wheat aphid biotypes. Regional and within-field aphid collections were screened against Russian wheat aphid-resistant wheat genotypes containing genes Dn3, Dn4, Dn6, Dn7, Dn9, CI2401; and resistant barley STARS 9301B. In 2010, all aphid collections from Texas were avirulent to the Dn4 resistance gene in wheat. Regional results revealed Dn4 avirulent RWA6 was widespread (55-84%) in populations infesting wheat in both regions. Biotypes RWA1, 2, and 3/7 were equally represented with percentages<20% each while RWA8 was rarely detected. Combining percentages of RWA1, 6, and 8 across regions to estimate avirulence to Dn4 gene revealed high percentages for both 2011 (64-80%) and 2013 (69-90%). In contrast, the biotype structure at the local level differed where biotype percentages varied up to ≥2-fold between fields. No new biotypes were detected; therefore, Dn7, CI2401, and STARS9301B remained resistant to all known Russian wheat aphid biotypes. This study documents a shift to Dn4 avirulent biotypes and serves as a valuable baseline for biotypic diversity in Russian wheat aphid populations prior to the deployment of new Russian wheat aphid-resistant wheat cultivars. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

  10. Construction of Injectable Double-Network Hydrogels for Cell Delivery.

    PubMed

    Yan, Yan; Li, Mengnan; Yang, Di; Wang, Qian; Liang, Fuxin; Qu, Xiaozhong; Qiu, Dong; Yang, Zhenzhong

    2017-07-10

    Herein we present a unique method of using dynamic cross-links, which are dynamic covalent bonding and ionic interaction, for the construction of injectable double-network (DN) hydrogels, with the objective of cell delivery for cartilage repair. Glycol chitosan and dibenzaldhyde capped poly(ethylene oxide) formed the first network, while calcium alginate formed the second one, and in the resultant DN hydrogel, either of the networks could be selectively removed. The moduli of the DN hydrogel were significantly improved compared to that of the parent single-network hydrogels and were tunable by changing the chemical components. In situ 3D cell encapsulation could be easily performed by mixing cell suspension to the polymer solutions and transferred through a syringe needle before sol-gel transition. Cell proliferation and mediated differentiation of mouse chondrogenic cells were achieved in the DN hydrogel extracellular matrix.

  11. 48 CFR 252.225-7012 - Preference for certain domestic commodities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., reused, or produced in the United States: (1) Food. (2) Clothing and the materials and components thereof... the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery, handwear, belts, badges, and insignia. (3)(i) Tents and structural components...

  12. 48 CFR 252.225-7012 - Preference for certain domestic commodities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., reused, or produced in the United States: (1) Food. (2) Clothing and the materials and components thereof... the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery, handwear, belts, badges, and insignia. (3)(i) Tents and structural components...

  13. Aging effects on the Binaural Interaction Component of the Auditory Brainstem Response in the Mongolian Gerbil: Effects of Interaural Time and Level Differences

    PubMed Central

    Laumen, Geneviève; Tollin, Daniel J.; Beutelmann, Rainer; Klump, Georg M.

    2016-01-01

    The effect of interaural time difference (ITD) and interaural level difference (ILD) on wave 4 of the binaural and summed monaural auditory brainstem responses (ABRs) as well as on the DN1 component of the binaural interaction component (BIC) of the ABR in young and old Mongolian gerbils (Meriones unguiculatus) was investigated. Measurements were made at a fixed sound pressure level (SPL) and a fixed level above visually detected ABR threshold to compensate for individual hearing threshold differences. In both stimulation modes (fixed SPL and fixed level above visually detected ABR threshold) an effect of ITD on the latency and the amplitude of wave 4 as well as of the BIC was observed. With increasing absolute ITD values BIC latencies were increased and amplitudes were decreased. ILD had a much smaller effect on these measures. Old animals showed a reduced amplitude of the DN1 component. This difference was due to a smaller wave 4 in the summed monaural ABRs of old animals compared to young animals whereas wave 4 in the binaural-evoked ABR showed no age-related difference. In old animals the small amplitude of the DN1 component was correlated with small binaural-evoked wave 1 and wave 3 amplitudes. This suggests that the reduced peripheral input affects central binaural processing which is reflected in the BIC. PMID:27173973

  14. 76 FR 66964 - Certain Inkjet Ink Cartridges With Printheads and Components Thereof; Notice of the Commission's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-723] Certain Inkjet Ink Cartridges With... exclusion order prohibiting importation of infringing inkjet ink cartridges with printheads and components... inkjet ink cartridges with printheads and components thereof by reason of infringement of various claims...

  15. 76 FR 38417 - In the Matter of Certain Multimedia Display and Navigation Devices and Systems, Components...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-694] In the Matter of Certain Multimedia Display and Navigation Devices and Systems, Components Thereof, and Products Containing Same; Notice of... importation of certain multimedia display and navigation devices and systems, components thereof, and products...

  16. 76 FR 25707 - In The Matter of Certain Multimedia Display and Navigation Devices and Systems, Components...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-694] In The Matter of Certain Multimedia Display and Navigation Devices and Systems, Components Thereof, and Products Containing Same; Notice of... multimedia display and navigation devices and systems, components thereof, and products containing same by...

  17. Conductance oscillations in molecularly linked Au nanoparticle film-superconductor systems.

    PubMed

    Dunford, Jeffrey L; Dhirani, Al-Amin

    2008-01-16

    Charge transport across a disordered normal-superconductor (DN-S) interface was studied using a macroscopic, molecularly linked Au nanoparticle film as the DN component. Low-temperature conductance versus voltage and magnetic field exhibit zero-bias and zero-field peaks, respectively. Importantly, the latter typically exhibit superimposed oscillations. Such oscillations are rarely seen in other DN-S systems and are remarkable given their robustness in these macroscopic films and interfaces. A number of observations indicate that conductance peaks and oscillations arise due to a 'reflectionless tunnelling' process. Scattering length scales extracted from the data using a reflectionless tunnelling picture are consistent with literature values. Factors resulting in the observation of oscillations in this system are discussed.

  18. 77 FR 40082 - Certain Gaming and Entertainment Consoles, Related Software, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... Commission remands for the ALJ to (1) apply the Commission's opinion in Certain Electronic Devices With Image Processing Systems, Components Thereof, and Associated Software, Inv. No. 337-TA-724, Comm'n Op. (Dec. 21...

  19. 76 FR 55704 - In the Matter of Certain Inkjet Ink Supplies and Components Thereof; Notice of a Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-08

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-730] In the Matter of Certain Inkjet Ink Supplies and Components Thereof; Notice of a Commission Determination Not To Review an Initial... importation, and sale within the United States after importation of certain inkjet ink supplies and components...

  20. 77 FR 23751 - Certain Food Waste Disposers and Components and Packaging Thereof; Institution of Investigation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-838] Certain Food Waste Disposers and Components... States after importation of certain food waste disposers and components and packaging thereof by reason... an industry in the United States exists as required by subsections (a)(1)(A) and (a)(2) of section...

  1. 78 FR 42107 - Certain Wireless Devices With 3G Capabilities and Components Thereof; Notice of Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-800] Certain Wireless Devices With 3G Capabilities and Components Thereof; Notice of Request for Statements on the Public Interest AGENCY: U.S..., specifically a limited exclusion order against certain wireless devices with 3G capabilities and components...

  2. 78 FR 1247 - Certain Electronic Devices, Including Wireless Communication Devices, Tablet Computers, Media...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... Wireless Communication Devices, Tablet Computers, Media Players, and Televisions, and Components Thereof... devices, including wireless communication devices, tablet computers, media players, and televisions, and... wireless communication devices, tablet computers, media players, and televisions, and components thereof...

  3. 78 FR 42800 - Certain Crawler Cranes and Components Thereof; Institution of Investigation Pursuant to United...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-17

    ... by reason of trade secret misappropriation, the threat or effect of which is to destroy or... cranes and components thereof by reason of the misappropriation of trade secrets, the threat or effect of...

  4. 77 FR 58406 - Certain LED Photographic Lighting Devices and Components Thereof; Notice of Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ...Notice is hereby given that the presiding administrative law judge (``ALJ'') has issued a Final Initial Determination and Recommended Determination on Remedy and Bonding in the above-captioned investigation. The Commission is soliciting comments on public interest issues raised by the recommended relief, specifically a general exclusion order against certain LED photographic lighting devices and components thereof. The ALJ alternatively recommended a limited exclusion order against certain LED photographic lighting devices and components thereof manufactured or sold by the respondents found in violation of 19 U.S.C. 1337.

  5. Tweezering the core of dendrimers: medium effect on the kinetic and thermodynamic properties.

    PubMed

    Giansante, Carlo; Mazzanti, Andrea; Baroncini, Massimo; Ceroni, Paola; Venturi, Margherita; Klärner, Frank-Gerrit; Vögtle, Fritz

    2009-10-02

    We have investigated the complex formation between dendritic guests and a molecular tweezer host by NMR, absorption, and emission spectroscopy as well as electrochemical techniques. The dendrimers are constituted by an electron-acceptor 4,4'-bipyridinium core appended with one (DnB(2+)) or two (Dn(2)B(2+)) polyaryl-ether dendrons. Tweezer T comprises a naphthalene and four benzene components bridged by four methylene groups. Medium effects on molecular recognition phenomena are discussed and provide insight into the conformation of dendrimers: change in solvent polarity from pure CH(2)Cl(2) to CH(2)Cl(2)/CH(3)CN mixtures and addition of tetrabutylammonium hexafluorophosphate (NBu(4)PF(6), up to 0.15 M), the supporting electrolyte used in the electrochemical measurements, have been investigated. The association constants measured in different media show the following trend: (i) they decrease upon increasing polarity of the solvent, as expected for host-guest complexes stabilized by electron donor-acceptor interactions; (ii) no effect of generation and number of dendrons (one for the DnB(2+) family and two for the Dn(2)B(2+) family) appended to the core is observed in higher polarity media; and (iii) in a low-polarity solvent, like CH(2)Cl(2), the stability of the inclusion complexes is higher for DnB(2+) dendrimers than for Dn(2)B(2+) ones, while within each dendrimer family it increases by decreasing dendron generation, and upon addition of NBu(4)PF(6). The last result has been ascribed to a partial dendron unfolding. Kinetic investigations performed in lower polarity media evidence that the rate constants of complex formation are slower for symmetric Dn(2)B(2+) dendrimers than for the nonsymmetric DnB(2+) ones, and that within the Dn(2)B(2+) family, they decrease by increasing dendron generation. The dependence of the rate constants for the formation and dissociation of the complexes upon addition of NBu(4)PF(6) has also been investigated and discussed.

  6. 78 FR 12354 - Certain Wireless Consumer Electronics Devices and Components Thereof; Commission Determination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-853] Certain Wireless Consumer Electronics Devices and Components Thereof; Commission Determination Concerning an Initial Determination Granting a Motion To Amend Complaint and Notice of Investigation AGENCY: U.S. International Trade...

  7. Aging effects on the binaural interaction component of the auditory brainstem response in the Mongolian gerbil: Effects of interaural time and level differences.

    PubMed

    Laumen, Geneviève; Tollin, Daniel J; Beutelmann, Rainer; Klump, Georg M

    2016-07-01

    The effect of interaural time difference (ITD) and interaural level difference (ILD) on wave 4 of the binaural and summed monaural auditory brainstem responses (ABRs) as well as on the DN1 component of the binaural interaction component (BIC) of the ABR in young and old Mongolian gerbils (Meriones unguiculatus) was investigated. Measurements were made at a fixed sound pressure level (SPL) and a fixed level above visually detected ABR threshold to compensate for individual hearing threshold differences. In both stimulation modes (fixed SPL and fixed level above visually detected ABR threshold) an effect of ITD on the latency and the amplitude of wave 4 as well as of the BIC was observed. With increasing absolute ITD values BIC latencies were increased and amplitudes were decreased. ILD had a much smaller effect on these measures. Old animals showed a reduced amplitude of the DN1 component. This difference was due to a smaller wave 4 in the summed monaural ABRs of old animals compared to young animals whereas wave 4 in the binaural-evoked ABR showed no age-related difference. In old animals the small amplitude of the DN1 component was correlated with small binaural-evoked wave 1 and wave 3 amplitudes. This suggests that the reduced peripheral input affects central binaural processing which is reflected in the BIC. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Robust Bonding of Tough Double Network Hydrogel to Bone

    NASA Astrophysics Data System (ADS)

    Nonoyama, Takayuki; Wada, Susumu; Kiyama, Ryuji; Kitamura, Nobuto; Kurokawa, Takayuki; Nakajima, Tasuku; Yasuda, Kazunori; Gong, Jian Ping

    Tough Double Network (DN) hydrogels are one of candidates as next-generation artificial cartilage from the viewpoints of low friction, water storage capability and toughness. For practical use, the hydrogel must be strongly fixed at the joint. However, strong fixation of such hydrogel to other materials (tissues) has not been achieved yet because the surface property of hydrogel is almost equal to water due to its high water content. Therefore, robust adhesion for fixation and low friction for lithe motion are trade-off relation. Here, we report robust fixation of hydroxyapatite (HAp) mineralized DN hydrogel to the bone without any toxicity. HAp is main inorganic component of bone tissues and has osteoconductive capability. After 4 weeks implantation of HAp/DN gel into rabbit femoral groove, The robust fixation between bone and HAp/DN gel, more than strength of gel matrix, was achieved. The methodology is universal for new biomaterials, which should be fixed on bone, such as ligament and tendon systems.

  9. Increased efficiency of the GABAA and GABAB receptor–mediated neurotransmission in the Ts65Dn mouse model of Down syndrome

    PubMed Central

    Kleschevnikov, Alexander M.; Belichenko, Pavel V.; Gall, Jessica; George, Lizzy; Nosheny, Rachel; Maloney, Michael T.; Salehi, Ahmad; Mobley, William C.

    2011-01-01

    Cognitive impairment in Down syndrome (DS) involves the hippocampus. In the Ts65Dn mouse model of DS, deficits in hippocampus-dependent learning and synaptic plasticity were linked to enhanced inhibition. However, the mechanistic basis of changes in inhibitory efficiency remains largely unexplored, and efficiency of the GABAergic synaptic neurotransmission has not yet been investigated in direct electrophysiological experiments. To investigate this important feature of neurobiology of DS, we examined synaptic and molecular properties of the GABAergic system in the dentate gyrus (DG) of adult Ts65Dn mice. Both GABAA and GABAB receptor-mediated components of evoked inhibitory postsynaptic currents (IPSCs) were significantly increased in Ts65Dn vs. control (2N) DG granule cells. These changes were unaccompanied by alterations in hippocampal levels of GABAA (α1, α2, α3, α5 and γ2) or GABAB (Gbr1a and Gbr1b) receptor subunits. Immunoreactivity for GAD65, a marker for GABAergic terminals, was also unchanged. In contrast, there was a marked change in functional parameters of GABAergic synapses. Paired stimulations showed reduced paired-pulse ratios of both GABAA and GABAB receptor-mediated IPSC components (IPSC2/IPSC1), suggesting an increase in presynaptic release of GABA. Consistent with increased gene dose, the level of the Kir3.2 subunit of potassium channels, effectors for postsynaptic GABAB receptors, was increased. This change was associated with enhanced postsynaptic GABAB/Kir3.2 signaling following application of the GABAB receptor agonist baclofen. Thus, both GABAA and GABAB receptor-mediated synaptic efficiency is increased in the Ts65Dn DG, thus likely contributing to deficient synaptic plasticity and poor learning in DS. PMID:22062771

  10. 77 FR 64546 - Certain Devices With Secure Communication Capabilities, Components Thereof, and Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-22

    ... Communication Capabilities, Components Thereof, and Products Containing Same; Institution of Investigation... VirnetX, Inc., of Zephyr Cove, Nevada and Science Applications International Corporation of McLean... sale within the United States after importation of certain devices with secure communication...

  11. 48 CFR 252.225-7012 - Preference for certain domestic commodities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... States: (1) Food. (2) Clothing and the materials and components thereof, other than sensors, electronics, or other items added to, and not normally associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery...

  12. 48 CFR 252.225-7012 - Preference for certain domestic commodities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... States: (1) Food. (2) Clothing and the materials and components thereof, other than sensors, electronics, or other items added to, and not normally associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery...

  13. 48 CFR 252.225-7012 - Preference for certain domestic commodities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... United States: (1) Food. (2) Clothing and the materials and components thereof, other than sensors, electronics, or other items added to, and not normally associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear...

  14. 78 FR 9740 - Certain Robotic Toys and Components Thereof; Institution of Investigation Pursuant to 19 U.S.C. 1337

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ... reason of misappropriation of trade secrets, the threat or effect of which is to destroy or substantially... robotic toys and components thereof by reason of misappropriation of trade secrets, the threat or effect...

  15. 78 FR 16296 - Certain Optoelectronic Devices for Fiber Optic Communications, Components Thereof, and Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-14

    ... Technologies'') to amend the complaint and notice of investigation (``NOI''). FOR FURTHER INFORMATION CONTACT... Fiber Optic Communications, Components Thereof, and Products Containing Same; Commission Determination Not To Review an Initial Determination Granting Complainants Avago Technologies General IP (Singapore...

  16. 77 FR 58576 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-21

    ... Devices, Portable Music and Data Processing Devices, Computers, and Components Thereof; Institution of... communication devices, portable music and data processing devices, computers, and components thereof by reason... certain wireless communication devices, portable music and data processing devices, computers, and...

  17. 78 FR 41950 - Certain Video Game Systems and Wireless Controllers and Components Thereof; Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-770] Certain Video Game Systems and Wireless Controllers and Components Thereof; Commission Determination To Review-In-Part a Remand Initial Determination; Schedule for Filing Written Submissions on Review for Remand Initial Determination and Final...

  18. 78 FR 57414 - Certain Video Game Systems and Wireless Controllers and Components Thereof, Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-770] Certain Video Game Systems and Wireless Controllers and Components Thereof, Commission Determination Finding No Violation of the Tariff Act of 1930 AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby...

  19. 78 FR 63492 - Certain Electronic Devices, Including Mobile Phones and Tablet Computers, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-847] Certain Electronic Devices, Including Mobile Phones and Tablet Computers, and Components Thereof; Notice of Request for Statements on the Public Interest AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is...

  20. 78 FR 1881 - Certain Food Waste Disposers and Components and Packaging Thereof; Notice of the Commission's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-838] Certain Food Waste Disposers and Components and Packaging Thereof; Notice of the Commission's Determination Not To Review Initial Determinations Granting Complainant's Motions To Partially Terminate the Investigation and To Withdraw the...

  1. 78 FR 77166 - Certain Optoelectronic Devices for Fiber Optic Communications, Components Thereof, and Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-860] Certain Optoelectronic Devices for Fiber Optic Communications, Components Thereof, and Products Containing the Same; Notice of Request for Statements on the Public Interest AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY...

  2. 77 FR 43118 - Certain Gaming and Entertainment Consoles, Related Software, and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-752] Certain Gaming and Entertainment Consoles, Related Software, and Components Thereof; Notice of Commission Determination To Review a Final Initial Determination Finding a Violation of Section 337; Remand of the Investigation to the...

  3. 77 FR 52759 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-745] Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and Components Thereof; Notice of... communication devices, portable music and data processing devices, computers and components thereof by reason of...

  4. 77 FR 51571 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-24

    ... Music and Data Processing Devices, Computers, and Components Thereof; Notice of Receipt of Complaint... complaint entitled Wireless Communication Devices, Portable Music and Data Processing Devices, Computers..., portable music and data processing devices, computers, and components thereof. The complaint names as...

  5. 76 FR 24051 - In the Matter of Certain Electronic Devices, Including Mobile Phones, Mobile Tablets, Portable...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-29

    ..., Including Mobile Phones, Mobile Tablets, Portable Music Players, and Computers, and Components Thereof... certain electronic devices, including mobile phones, mobile tablets, portable music players, and computers... mobile phones, mobile tablets, portable music players, and computers, and components thereof that...

  6. 78 FR 3449 - Certain Microprocessors, Components Thereof, and Products Containing Same; Request for Statements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-16

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-781] Certain Microprocessors, Components Thereof, and Products Containing Same; Request for Statements on the Public Interest AGENCY: U.S... a limited exclusion order as to subject Intel microprocessors, but that implementation be delayed...

  7. 78 FR 71643 - Certain Wireless Consumer Electronics Devices and Components Thereof; Commission Determination To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... Electronics Devices and Components Thereof; Commission Determination To Review in Part A Final Initial... sale within the United States after importation of certain wireless consumer electronics devices and... Electronics, Inc. of Seoul, Korea and LG Electronics U.S.A., Inc. of Englewood Cliffs, New Jersey...

  8. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR... samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in... additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color...

  9. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR... samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in... additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color...

  10. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR... samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in... additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color...

  11. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR... samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in... additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color...

  12. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR... samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in... additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color...

  13. 75 FR 42783 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-22

    ... Re Certain Flat Panel Digital Televisions and Components Thereof''; the Commission is soliciting... importation of certain flat panel digital televisions and components thereof. The complaint names as..., competitive conditions in the United States economy, the production of like or directly competitive articles...

  14. 75 FR 51286 - Certain Flat Panel Digital Televisions and Components Thereof; Notice of Investigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-733] Certain Flat Panel Digital Televisions and... importation, and the sale within the United States after importation of certain flat panel digital televisions... after importation of certain flat panel digital televisions and components thereof that infringe one or...

  15. 78 FR 2281 - Certain Robotic Toys and Components Thereof; Notice of Receipt of Complaint; Solicitation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-10

    ... INTERNATIONAL TRADE COMMISSION [Docket No. 2930] Certain Robotic Toys and Components Thereof.... International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International.... International Trade Commission, 500 E Street SW., Washington, DC 20436, telephone (202) 205-2000. The public...

  16. 77 FR 28622 - Certain Gaming and Entertainment Consoles, Related Software, and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-15

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-752] Certain Gaming and Entertainment Consoles, Related Software, and Components Thereof; Notice of Request for Statements on the Public Interest AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the...

  17. 76 FR 69762 - Limited Exclusion and Cease and Desist Orders; Terminations of Investigations: Certain Biometric...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ..., Associated Software, and Products Containing the Same AGENCY: U.S. International Trade Commission. ACTION..., components thereof, associated software, and products containing the same by reason of infringement of..., components thereof, associated software, and products containing the same that infringe one or more of claims...

  18. 78 FR 31576 - Enforcement Proceeding; Certain Two-Way Global Satellite Communication Devices, System and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ...-Way Global Satellite Communication Devices, System and Components Thereof; Notice of Institution of...-confidential documents filed in connection with this investigation are or will be available for inspection... importation of certain two-way global satellite communication devices, system and components thereof by reason...

  19. 77 FR 68829 - Certain Electronic Digital Media Devices and Components Thereof; Notice of Request for Statements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-796] Certain Electronic Digital Media... electronic digital media devices and components thereof imported by respondents Samsung Electronics Co, Ltd... Samsung. FOR FURTHER INFORMATION CONTACT: Cathy Chen, Office of the General Counsel, U.S. International...

  20. 77 FR 808 - Certain Video Analytics Software, Systems, Components Thereof, and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-06

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-795] Certain Video Analytics Software... filed by ObjectVideo, Inc. of Reston, Virginia. 76 FR 45859 (Aug. 1, 2011). The complaint, as amended... certain video analytics software, systems, components thereof, and products containing same by reason of...

  1. 77 FR 75659 - Certain Video Analytics Software, Systems, Components Thereof, and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-852] Certain Video Analytics Software..., 2012, based on a complaint filed by ObjectVideo, Inc. (``ObjectVideo'') of Reston, Virginia. 77 FR... United States after importation of certain video analytics software systems, components thereof, and...

  2. 77 FR 74220 - Certain Digital Photo Frames and Image Display Devices and Components Thereof; Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-807] Certain Digital Photo Frames and Image Display Devices and Components Thereof; Commission Determination Not To Review an Initial... importation, and the sale within the United States after importation of certain digital photo frames and image...

  3. 76 FR 52970 - In the Matter of Certain Biometric Scanning Devices, Components Thereof, Associated Software, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-720] In the Matter of Certain Biometric... accessing its Internet server at http://www.usitc.gov . The public record for this investigation may be... certain biometric scanning devices, components thereof, associated software, and products containing the...

  4. 78 FR 50445 - Certain Computers and Computer Peripheral Devices and Components Thereof and Products Containing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-841] Certain Computers and Computer Peripheral Devices and Components Thereof and Products Containing the Same Request for Statements on the Public Interest AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby...

  5. The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

    PubMed

    Timar, Bogdan; Timar, Romulus; Gaiță, Laura; Oancea, Cristian; Levai, Codrina; Lungeanu, Diana

    2016-01-01

    Diabetic neuropathy (DN) is a prevalent complication of Type 2 Diabetes Mellitus (T2DM) with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN's three major components: sensitive (lack of motion associated sensory), motor (impairments in movement coordination) and autonomic (the presence of postural hypotension), the presence of DN may impair the balance in the affected patients. Our study's main aim is to evaluate the possible association between the presence and severity of DN and both the balance impairment and the risk of falls in patients with T2DM. In this cross-sectional study we enrolled, according to a consecutive-case population-based setting 198 patients with T2DM. The presence and severity of DN was evaluated using the Michigan Neuropathy Screening Instrument, a tool which allows both diagnosing and severity staging of DN. The balance impairment and the risk of falls were evaluated using four validated and standardized tools: Berg Balance Scale (BBS), Timed-up and Go test (TUG), Single Leg Stand test (SLS) and Fall Efficacy Scale (FES-I). The presence of DN was associated with significant decreases in the BBS score (40.5 vs. 43.7 points; p<0.001) and SLS time (9.3 vs. 10.3 seconds; p = 0.003) respectively increases in TUG time (8.9 vs. 7.6 seconds; p = 0.002) and FES-I score (38 vs. 33 points; p = 0.034). The MNSI score was reverse and significantly correlated with both BBS score (Spearman's r = -0.479; p<0.001) and SLS time (Spearman's r = -0.169; p = 0.017). In the multivariate regression model, we observed that patient's age, DN severity and depression's symptoms acted as independent, significant predictors for the risk of falls in patients with T2DM. The presence of DN in patients with DM is associated with impaired balance and with a consecutively increase in the risk of falls.

  6. Myocardin-Related Transcription Factor A Epigenetically Regulates Renal Fibrosis in Diabetic Nephropathy

    PubMed Central

    Xu, Huihui; Wu, Xiaoyan; Qin, Hao; Tian, Wenfang; Chen, Junliang; Sun, Lina; Fang, Mingming

    2015-01-01

    Diabetic nephropathy (DN) is one of the most common complications associated with diabetes and characterized by renal microvascular injury along with accelerated synthesis of extracellular matrix proteins causing tubulointerstitial fibrosis. Production of type I collagen, the major component of extracellular matrix, is augmented during renal fibrosis after chronic exposure to hyperglycemia. However, the transcriptional modulator responsible for the epigenetic manipulation leading to induction of type I collagen genes is not clearly defined. We show here that tubulointerstitial fibrosis as a result of DN was diminished in myocardin-related transcription factor A (MRTF-A) -deficient mice. In cultured renal tubular epithelial cells and the kidneys of mice with DN, MRTF-A was induced by glucose and synergized with glucose to activate collagen transcription. Notably, MRTF-A silencing led to the disappearance of prominent histone modifications indicative of transcriptional activation, including acetylated histone H3K18/K27 and trimethylated histone H3K4. Detailed analysis revealed that MRTF-A recruited p300, a histone acetyltransferase, and WD repeat-containing protein 5 (WDR5), a key component of the histone H3K4 methyltransferase complex, to the collagen promoters and engaged these proteins in transcriptional activation. Estradiol suppressed collagen production by dampening the expression and binding activity of MRTF-A and interfering with the interaction between p300 and WDR5 in renal epithelial cells. Therefore, targeting the MRTF-A–associated epigenetic machinery might yield interventional strategies against DN-associated renal fibrosis. PMID:25349198

  7. 76 FR 23624 - In the Matter of Certain Video Game Systems and Wireless Controllers and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-770] In the Matter of Certain Video Game Systems... importation of certain video game systems and wireless controllers and components thereof by reason of... sale within the United States after importation of certain video game systems and wireless controllers...

  8. 77 FR 8898 - Certain Coaxial Cable Connectors and Components Thereof and Products Containing Same; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-650] Certain Coaxial Cable Connectors and... States after importation of certain coaxial cable connectors and components thereof and products... an advisory opinion under Commission Rule 210.79 (19 CFR 210.79) that would declare that its coaxial...

  9. 75 FR 28651 - In the Matter of Certain Electronic Paper Towel Dispensing Devices and Components Thereof; Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-21

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-718] In the Matter of Certain Electronic Paper Towel Dispensing Devices and Components Thereof; Notice of Investigation AGENCY: International Trade... that a complaint was filed with the U.S. International Trade Commission on April 19, 2010, under...

  10. 75 FR 63857 - In the Matter of: Certain Digital Televisions and Components Thereof; Notice of Investigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-18

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-742] In the Matter of: Certain Digital Televisions... importation, and the sale within the United States after importation of certain digital televisions and... sale within the United States after importation of certain digital televisions and components thereof...

  11. 75 FR 68619 - In the Matter of Certain Wireless Communication Devices, Portable Music and Data Processing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ... Communication Devices, Portable Music and Data Processing Devices, Computers and Components Thereof; Notice of... within the United States after importation of certain wireless communication devices, portable music and... music and data processing devices, computers and components thereof that infringe one or more of claim...

  12. 75 FR 77904 - In the Matter of Certain Turbomachinery Blades, Engines and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-751] In the Matter of Certain Turbomachinery Blades, Engines and Components Thereof; Notice of Investigation AGENCY: U.S. International Trade... that a complaint was filed with the U.S. International Trade Commission on November 5, 2010, under...

  13. 76 FR 2707 - In the Matter of Certain Data Storage Products and Components Thereof; Notice of Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-14

    ... complaint filed by Data Network Storage, LLC of Newport Beach, California (``DNS''). 75 FR 71736 (Nov. 24... States after importation of certain data storage products and components thereof by reason of... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-748] In the Matter of Certain Data...

  14. 78 FR 52212 - Certain Certain Ink Application Devices and Components Thereof and Methods of Using the Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-832] Certain Certain Ink Application... certain ink application devices and components thereof and methods of using the same by reason of... determination of violation against T-Tech or, in the alternative, granting Complainants' motion for an ID...

  15. 76 FR 81527 - Certain Wireless Devices with 3G Capabilities and Components Thereof; Determination Not to Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-800] Certain Wireless Devices with 3G Capabilities and Components Thereof; Determination Not to Review Initial Determination Granting Motion for... importation, and the sale within the United States after importation of certain wireless devices with 3G...

  16. Method for forming nuclear fuel containers of a composite construction and the product thereof

    DOEpatents

    Cheng, Bo-Ching; Rosenbaum, Herman S.; Armijo, Joseph S.

    1984-01-01

    An improved method for producing nuclear fuel containers of a composite construction having components providing therein a barrier system for resisting destructive action by volatile fission products or impurities and also interdiffusion of metal constituents, and the product thereof. The composite nuclear fuel containers of the method comprise a casing of zirconium or alloy thereof with a layer of copper overlying an oxidized surface portion of the zirconium or alloy thereof.

  17. 75 FR 17435 - In the Matter of Certain Inkjet Ink Cartridges With Printheads and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-711] In the Matter of Certain Inkjet Ink... importation, and the sale within the United States after importation of certain inkjet ink cartridges with... importation of certain inkjet cartridges with printheads or components thereof that infringe one or more of...

  18. 76 FR 45616 - Certain Digital Set-Top Boxes and Components Thereof; Notice of Commission Determination Not To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-712] Certain Digital Set-Top Boxes and... the United States after importation of certain digital set- top boxes and components thereof, that... welfare, (2) competitive conditions in the U.S. economy, (3) U.S. production of articles that are like or...

  19. 75 FR 49945 - In the Matter of Certain Hybrid Electric Vehicles and Components Thereof; Notice of Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... Toyota hybrid vehicles of claims of U.S. Patent No. 5,343,970. On July 19, 2010, Paice and Toyota moved... INTERNATIONAL TRADE COMMISSION [ Inv. No. 337-TA-688] In the Matter of Certain Hybrid Electric Vehicles and Components Thereof; Notice of Commission Determination Not To Review an Initial Determination...

  20. 77 FR 1725 - Certain Blu-Ray Disc Players, Components Thereof and Products Containing Same; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ..., Components Thereof and Products Containing Same; Notice of Institution of Investigation AGENCY: U.S... the U.S. International Trade Commission on December 5, 2011, under section 337 of the Tariff Act of 1930, as amended, 19 U.S.C. 1337, on behalf of Walker Digital, LLC, of Stamford, Connecticut. Letters...

  1. 75 FR 41889 - In the Matter of Certain Collaborative System Products and Components Thereof (II); Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-728] In the Matter of Certain Collaborative System Products and Components Thereof (II); Notice of Investigation AGENCY: U.S. International Trade Commission... complaint was filed with the U.S. International Trade Commission on June 15, 2010, under section 337 of the...

  2. 77 FR 21994 - Certain Digital Photo Frames and Image Display Devices and Components Thereof; Notice of Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... Image Display Devices and Components Thereof; Notice of Request for Written Submissions on Remedy, the... importation, and the sale within the United States after importation of certain digital photo frames and image... the President, has 60 days to approve or disapprove the Commission's action. See section 337(j), 19 U...

  3. Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists

    PubMed Central

    Kleschevnikov, A.M.; Belichenko, P.V.; Faizi, M.; Jacobs, L.F.; Htun, K.; Shamloo, M.; Mobley, W.C.

    2012-01-01

    Cognitive impairment in Down syndrome (DS) is characterized by deficient learning and memory. Mouse genetic models of DS exhibit impaired cognition in hippocampally mediated behavioral tasks and reduced synaptic plasticity of hippocampal pathways. Enhanced efficiency of GABAergic neurotransmission was implicated in those changes. We have recently shown that signaling through postsynaptic GABAB receptors is significantly increased in the dentate gyrus (DG) of Ts65Dn mice, a genetic model of DS. Here we examined a role for GABAB receptors in cognitive deficits in DS by defining the effect of selective GABAB receptor antagonists on behavior and synaptic plasticity of adult Ts65Dn mice. Treatment with the GABAB receptor antagonist CGP55845 restored memory of Ts65Dn mice in the novel place recognition, novel object recognition and contextual fear conditioning tasks, but did not affect locomotion and performance in T-maze. The treatment increased hippocampal levels of brain-derived neurotrophic factor (BDNF), equally in 2N and Ts65Dn mice. In hippocampal slices, treatment with the GABAB receptor antagonists CGP55845 or CGP52432 enhanced long-term potentiation (LTP) in the Ts65Dn DG. The enhancement of LTP was accompanied by an increase in the NMDA receptor-mediated component of the tetanus-evoked responses. These findings are evidence for a contribution of GABAB receptors to changes in hippocampal-based cognition in the Ts65Dn mouse. The ability to rescue cognitive performance through treatment with selective GABAB receptor antagonists motivates studies to further explore the therapeutic potential of these compounds in people with DS. PMID:22764230

  4. 78 FR 36573 - Certain Digital Media Devices, Including Televisions, Blu-Ray Disc Players, Home Theater Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... Thereof and Associated Software AGENCY: U.S. International Trade Commission. ACTION: Notice, Institution... thereof and associated software, by reason of infringement of U.S. Patent No. 8,028,323 (``the `323 patent... mobile phones, components thereof and associated software by reason of infringement of one or more of...

  5. c-Myc-Induced Survivin Is Essential for Promoting the Notch-Dependent T Cell Differentiation from Hematopoietic Stem Cells

    PubMed Central

    Haque, Rizwanul; Song, Jianyong; Haque, Mohammad; Lei, Fengyang; Sandhu, Praneet; Ni, Bing; Zheng, Songguo; Fang, Deyu; Yang, Jin-Ming; Song, Jianxun

    2017-01-01

    Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c-Myc is a key mediator of the Notch signaling–regulated T cell differentiation. In a well-established in vitro differentiation model of T lymphocytes from hematopoietic stem cells, we showed that Notch1 and 4 directly promoted c-Myc expression; dominant-negative (DN) c-Myc inhibited early T cell differentiation. Moreover, the c-Myc expression activated by Notch signaling increased the expression of survivin, an inhibitor of apoptosis (IAP) protein. We further demonstrated that over-expression of c-Myc increased the abundance of survivin and the T cell differentiation thereof, whereas dn c-Myc reduced survivin levels and concomitantly retarded the differentiation. The c-Myc–dependent survivin induction is functionally germane, because Notch-dependent T cell differentiation was canceled by the depletion of survivin. These results identify both c-Myc and survivin as important mediators of the Notch signaling–regulated differentiation of T lymphocytes from hematopoietic stem cells. PMID:28272325

  6. 76 FR 70490 - Certain Electronic Devices With Graphics Data Processing Systems, Components Thereof, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... Graphics Data Processing Systems, Components Thereof, and Associated Software; Institution of Investigation... associated software by reason of infringement of certain claims of U.S. Patent No. 5,945,997 (``the `997... software that infringe one or more of claims 1, 3-5, 9, and 16 of the `997 patent; claims 1, 5, and 9 of...

  7. Protein Dynamics Associated with Failed and Rescued Learning in the Ts65Dn Mouse Model of Down Syndrome

    PubMed Central

    Ahmed, Md. Mahiuddin; Dhanasekaran, A. Ranjitha; Block, Aaron; Tong, Suhong; Costa, Alberto C. S.; Stasko, Melissa; Gardiner, Katheleen J.

    2015-01-01

    Down syndrome (DS) is caused by an extra copy of human chromosome 21 (Hsa21). Although it is the most common genetic cause of intellectual disability (ID), there are, as yet, no effective pharmacotherapies. The Ts65Dn mouse model of DS is trisomic for orthologs of ∼55% of Hsa21 classical protein coding genes. These mice display many features relevant to those seen in DS, including deficits in learning and memory (L/M) tasks requiring a functional hippocampus. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist, memantine, was shown to rescue performance of the Ts65Dn in several L/M tasks. These studies, however, have not been accompanied by molecular analyses. In previous work, we described changes in protein expression induced in hippocampus and cortex in control mice after exposure to context fear conditioning (CFC), with and without memantine treatment. Here, we extend this analysis to Ts65Dn mice, measuring levels of 85 proteins/protein modifications, including components of MAP kinase and MTOR pathways, and subunits of NMDA receptors, in cortex and hippocampus of Ts65Dn mice after failed learning in CFC and after learning was rescued by memantine. We show that, compared with wild type littermate controls, (i) of the dynamic responses seen in control mice in normal learning, >40% also occur in Ts65Dn in failed learning or are compensated by baseline abnormalities, and thus are considered necessary but not sufficient for successful learning, and (ii) treatment with memantine does not in general normalize the initial protein levels but instead induces direct and indirect responses in approximately half the proteins measured and results in normalization of the endpoint protein levels. Together, these datasets provide a first view of the complexities associated with pharmacological rescue of learning in the Ts65Dn. Extending such studies to additional drugs and mouse models of DS will aid in identifying pharmacotherapies for effective clinical trials. PMID:25793384

  8. 78 FR 5207 - Certain Led Photographic Lighting Devices and Components Thereof; Commission's Final...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-24

    ...Notice is hereby given that the U.S. International Trade Commission has found a violation of section 337 in this investigation and has issued a general exclusion order prohibiting importation of infringing LED photographic lighting devices and components thereof. The Commission has also determined to terminate certain respondents on the basis of a consent order stipulation, and has issued a consent order.

  9. 78 FR 8191 - Certain Wireless Devices With 3G and/or 4G Capabilities and Components Thereof; Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-868] Certain Wireless Devices With 3G and... importation, and the sale within the United States after importation of certain wireless devices with 3G and... devices with 3G and/or 4G capabilities and components thereof by reason of infringement of one or more of...

  10. Composite construction for nuclear fuel containers

    DOEpatents

    Cheng, Bo-Ching [Fremont, CA; Rosenbaum, Herman S [Fremont, CA; Armijo, Joseph S [Saratoga, CA

    1987-01-01

    An improved method for producing nuclear fuel containers of a composite construction having components providing therein a barrier system for resisting destructive action by volatile fission products or impurities and also interdiffusion of metal constituents, and the product thereof. The composite nuclear fuel containers of the method comprise a casing of zirconium or alloy thereof with a layer of copper overlying an oxidized surface portion of the zirconium or alloy thereof.

  11. Composite construction for nuclear fuel containers

    DOEpatents

    Cheng, B. C.; Rosenbaum, H. S.; Armijo, J. S.

    1987-04-21

    Disclosed is an improved method for producing nuclear fuel containers of a composite construction having components providing therein a barrier system for resisting destructive action by volatile fission products or impurities and also interdiffusion of metal constituents, and the product thereof. The composite nuclear fuel containers of the method comprise a casing of zirconium or alloy thereof with a layer of copper overlying an oxidized surface portion of the zirconium or alloy thereof. 1 fig.

  12. Leaching of DOC, DN, and inorganic constituents from scrap tires.

    PubMed

    Selbes, Meric; Yilmaz, Ozge; Khan, Abdul A; Karanfil, Tanju

    2015-11-01

    One concern for recycle and reuse of scrap tires is the leaching of tire constituents (organic and inorganic) with time, and their subsequent potential harmful impacts in environment. The main objective of this study was to examine the leaching of dissolved organic carbon (DOC), dissolved nitrogen (DN), and selected inorganic constituents from scrap tires. Different sizes of tire chips and crumb rubber were exposed to leaching solutions with pH's ranging from 3.0 to 10.0 for 28days. The leaching of DOC and DN were found to be higher for smaller size tire chips; however, the leaching of inorganic constituents was independent of the size. In general, basic pH conditions increased the leaching of DOC and DN, whereas acidic pH conditions led to elevated concentrations of metals. Leaching was minimal around the neutral pH values for all the monitored parameters. Analysis of the leaching rates showed that components associated with the rubbery portion of the tires (DOC, DN, zinc, calcium, magnesium, etc.) exhibited an initial rapid followed by a slow release. On the other hand, a constant rate of leaching was observed for iron and manganese, which are attributed to the metal wires present inside the tires. Although the total amounts that leached varied, the observed leaching rates were similar for all tire chip sizes and leaching solutions. Operation under neutral pH conditions, use of larger size tire chips, prewashing of tires, and removal of metal wires prior to application will reduce the impact of tire recycle and reuse. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Two-Dimensional Lead Halide Perovskites Templated by a Conjugated Asymmetric Diammonium.

    PubMed

    Hautzinger, Matthew P; Dai, Jun; Ji, Yujin; Fu, Yongping; Chen, Jie; Guzei, Ilia A; Wright, John C; Li, Youyong; Jin, Song

    2017-12-18

    We report novel two-dimensional lead halide perovskite structures templated by a unique conjugated aromatic dication, N,N-dimethylphenylene-p-diammonium (DPDA). The asymmetrically substituted primary and tertiary ammoniums in DPDA facilitate the formation of two-dimensional network (2DN) perovskite structures incorporating a conjugated dication between the PbX 4 2- (X = Br, I) layers. These 2DN structures of (DPDA)PbI 4 and (DPDA)PbBr 4 were characterized by single-crystal X-ray diffraction, showing uniquely low distortions in the Pb-X-Pb bond angle for 2D perovskites. The Pb-I-Pb bond angle is very close to ideal (180°) for a 2DN lead iodide perovskite, which can be attributed to the ability of the rigid diammonium DPDA to insert into the PbX 6 2- octahedral pockets. Optical characterization of (DPDA)PbI 4 shows an excitonic absorption peak at 2.29 eV (541 nm), which is red-shifted in comparison to similar 2DN lead iodide structures. Temperature-dependent photoluminescence of both compounds reveals both a self-trapped exciton and free exciton emission feature. The reduced exciton absorption energy and emission properties are attributed to the dication-induced structural order of the inorganic PbX 4 2- layers. DFT calculation results suggest mixing of the conjugated organic orbital component in the valence band of these 2DN perovskites. These results demonstrate a rational new strategy to incorporate conjugated organic dications into hybrid perovskites and will spur spectroscopic investigations of these compounds as well as optoelectronic applications.

  14. Accumulation of worn-out GBM material substantially contributes to mesangial matrix expansion in diabetic nephropathy.

    PubMed

    Kriz, Wilhelm; Löwen, Jana; Federico, Giuseppina; van den Born, Jacob; Gröne, Elisabeth; Gröne, Hermann Josef

    2017-06-01

    Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of diabetic nephropathy (DN), generally considered to emerge from different sites of overproduction: GBM components from podocytes and mesangial matrix from mesangial cells. Reevaluation of 918 biopsies with DN revealed strong evidence that these mechanisms are connected to each other, wherein excess GBM components fail to undergo degradation and are deposited in the mesangium. These data do not exclude that mesangial cells also synthesize components that contribute to the accumulation of matrix in the mesangium. Light, electron microscopic, immunofluorescence, and in situ hybridization studies clearly show that the thickening of the GBM is due not only to overproduction of components of the mature GBM (α3 and α5 chains of collagen IV and agrin) by podocytes but also to resumed increased synthesis of the α1 chain of collagen IV and of perlecan by endothelial cells usually seen during embryonic development. We hypothesize that these abnormal production mechanisms are caused by different processes: overproduction of mature GBM-components by the diabetic milieu and regression of endothelial cells to an embryonic production mode by decreased availability of mediators from podocytes. Copyright © 2017 the American Physiological Society.

  15. Metal nanoparticle deposited inorganic nanostructure hybrids, uses thereof and processes for their preparation

    DOEpatents

    Tenne, Reshef; Tsverin, Yulia; Burghaus, Uwe; Komarneni, Mallikharjuna Rao

    2016-01-26

    This invention relates to a hybrid component comprising at least one nanoparticle of inorganic layered compound (in the form of fullerene-like structure or nanotube), and at least one metal nanoparticle, uses thereof as a catalyst, (e.g. photocatalysis) and processes for its preparation.

  16. Component-based control of oil-gas-water mixture composition in pipelines

    NASA Astrophysics Data System (ADS)

    Voytyuk, I. N.

    2018-03-01

    The article theoretically proves the method for measuring the changes in content of oil, gas and water in pipelines; also the measurement system design for implementation thereof is discussed. An assessment is presented in connection with random and systemic errors for the future system, and recommendations for optimization thereof are presented.

  17. 76 FR 76126 - Uncovered Innerspring Units from the People's Republic of China: Preliminary Results and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... merchandise into the United States exported by Reztec. Consequently, we intend to rescind the review, in part... at 870; Tapered Roller Bearings and Parts Thereof, Finished and Unfinished, From Japan, and Tapered Roller Bearings, Four Inches or Less in Outside Diameter, and Components Thereof, From Japan; Preliminary...

  18. Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses

    PubMed Central

    Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

    2017-01-01

    Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs, including DnARF1, DnARF4, and DnARF6, were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1, DnARF4, and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale. To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment. PMID:28471373

  19. Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses.

    PubMed

    Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

    2017-05-04

    Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs , including DnARF1 , DnARF4 , and DnARF6 , were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1 , DnARF4 , and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale . To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment.

  20. De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation.

    PubMed

    Tikkanen, Jussi M; Singer, Lianne G; Kim, S Joseph; Li, Yanhong; Binnie, Matthew; Chaparro, Cecilia; Chow, Chung-Wai; Martinu, Tereza; Azad, Sassan; Keshavjee, Shaf; Tinckam, Kathryn

    2016-09-01

    Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear. To describe the incidence, characteristics, and impact of dnDSA after lung transplantation. We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis. The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44-185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). This association appeared to be driven by the development of DQ-dnDSA. dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.

  1. Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy

    PubMed Central

    Sun, Guang-dong; Li, Chao-yuan; Cui, Wen-peng; Guo, Qiao-yan; Dong, Chang-qing; Zou, Hong-bin; Liu, Shu-jun; Dong, Wen-peng; Miao, Li-ning

    2016-01-01

    Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20–40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN. PMID:26649322

  2. Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity

    USGS Publications Warehouse

    House, M.L.; Kim, C.H.; Reno, P.W.

    1998-01-01

    Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

  3. Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy.

    PubMed

    Sun, Guang-dong; Li, Chao-yuan; Cui, Wen-peng; Guo, Qiao-yan; Dong, Chang-qing; Zou, Hong-bin; Liu, Shu-jun; Dong, Wen-peng; Miao, Li-ning

    2016-01-01

    Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20-40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN.

  4. Antithrombogenic and antibiotic composition and methods of preparation thereof

    DOEpatents

    Hermes, Robert E.

    1990-01-01

    Antithrombogenic and antibiotic composition of matter and method of preparation thereof. A random copolymer of a component of garlic and a biocompatible polymer has been prepared and found to exhibit antithrombogenic and antibiotic properties. Polymerization occurs selectively at the vinyl moiety in 2-vinyl-4H-1,3-dithiin when copolymerized with N-vinyl pyrrolidone.

  5. [Financing Regional Dementia Networks in Germany: Determinants of Sustainable Healthcare Networks].

    PubMed

    Michalowsky, B; Wübbeler, M; Thyrian, J R; Holle, B; Gräske, J; Schäfer-Walkmann, S; Fleßa, S; Hoffmann, W

    2017-12-01

    Analysis of practice-based financing concepts in German dementia networks (DN); Provision of sustainable financing structures and their determinants in DN. Qualitative expert interviews with leaders of 13 DN were conducted. A semi-structured interview guide was used to analyse four main topics: Finance-related organization, cost, sources of funding and financial sustainability. DN were primarily financed by membership fees, earnings of services provided, public funds and payments by municipalities or health care providers. 63% of the DN reported a financial sustainability. Funds to support the interpersonal expanding, a mix of internal and external financing sources and investments of the municipality were determinants of a sustainable financing. Overall, DN in rural areas seemed to be disadvantaged due to a lack of potential linkable service providers. DN in urban regions are more likely able to gather sustainable funding resources. A minimum funding of 50.000 €/year for human resources coordinating the DN, seems to be a threshold for a sustainable DN. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Retracted: Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population.

    PubMed

    Liu, Guohui; Zhou, Tian-Biao; Jiang, Zongpei; Zheng, Dongwen

    2015-03-01

    The association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism with type-2 diabetic nephropathy (T2DN) susceptibility and the risk of type-2 diabetes mellitus (T2DM) developing into T2DN in Caucasian populations is still controversial. A meta-analysis was performed to evaluate the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Sixteen articles were identified for the analysis of the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. Sensitivity analysis according to sample size of case (<100 vs. ≥100) was also performed, and the results were similar to the non-sensitivity analysis. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. However, more studies should be performed in the future. © The Author(s) 2014.

  7. Growth, yield, and disease resistance of 7- to 12-year-old poplar clones in the north central United States.

    Treesearch

    D.A. Netzer; D.N. Tolsted; M. E. Ostry; J. G. Isebrands; D.E. Riemenschneider; K.T. Ward

    2002-01-01

    Summarizes growth, yield, and disease resistance of 95 poplar clones at or near rotation age (culmination of mean annual increment). Plantations were established from 1986 to 1992 in Wisconsin, Minnesota, North and South Dakota. Clones DN164, DN177, DN154, NM2, NE264, DN170, and DN21 are recommended for further testing.

  8. Hydroxyapatite-coated double network hydrogel directly bondable to the bone: Biological and biomechanical evaluations of the bonding property in an osteochondral defect.

    PubMed

    Wada, Susumu; Kitamura, Nobuto; Nonoyama, Takayuki; Kiyama, Ryuji; Kurokawa, Takayuki; Gong, Jian Ping; Yasuda, Kazunori

    2016-10-15

    We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2weeks, and the osteoid tissue was mineralized at 4weeks. The push-out load of the HAp/DN gel averaged 37.54N and 42.15N at 4 and 12weeks, respectively, while the push-out load of the DN gel averaged less than 5N. The bonding area of the HAp/DN gel to the bone was above 80% by 4weeks, and above 90% at 12weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy

    PubMed Central

    Soler, María José; Riera, Marta; Batlle, Daniel

    2012-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes. PMID:22461787

  10. Antithrombogenic and antibiotic compositions and methods of preparation thereof

    DOEpatents

    Hermes, R.E.

    1988-04-19

    Antithrombogenic and antibiotic composition of matter and method of preparation thereof. A random copolymer of a component of garlic and a biocompatible polymer has been prepared and found to exhibit antithrombogenic and antibiotic properties. Polymerization occurs selectively at the vinyl moiety in 2-vinyl-4H-1,3-dithiin when copolymerized with N-vinyl pyrrolidone. 4 figs., 2 tabs.

  11. Improved Neuroimaging Atlas of the Dentate Nucleus.

    PubMed

    He, Naying; Langley, Jason; Huddleston, Daniel E; Ling, Huawei; Xu, Hongmin; Liu, Chunlei; Yan, Fuhua; Hu, Xiaoping P

    2017-12-01

    The dentate nucleus (DN) of the cerebellum is the major output nucleus of the cerebellum and is rich in iron. Quantitative susceptibility mapping (QSM) provides better iron-sensitive MRI contrast to delineate the boundary of the DN than either T 2 -weighted images or susceptibility-weighted images. Prior DN atlases used T 2 -weighted or susceptibility-weighted images to create DN atlases. Here, we employ QSM images to develop an improved dentate nucleus atlas for use in imaging studies. The DN was segmented in QSM images from 38 healthy volunteers. The resulting DN masks were transformed to a common space and averaged to generate the DN atlas. The center of mass of the left and right sides of the QSM-based DN atlas in the Montreal Neurological Institute space was -13.8, -55.8, and -36.4 mm, and 13.8, -55.7, and -36.4 mm, respectively. The maximal probability and mean probability of the DN atlas with the individually segmented DNs in this cohort were 100 and 39.3%, respectively, in contrast to the maximum probability of approximately 75% and the mean probability of 23.4 to 33.7% with earlier DN atlases. Using QSM, which provides superior iron-sensitive MRI contrast for delineating iron-rich structures, an improved atlas for the dentate nucleus has been generated. The atlas can be applied to investigate the role of the DN in both normal cortico-cerebellar physiology and the variety of disease states in which it is implicated.

  12. Incidence and Factors Associated with De Novo DSA After BK Viremia in Renal Transplant Recipients.

    PubMed

    Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Graviss, Edward A; Nguyen, Duc; Gaber, A Osama

    2016-01-01

    BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted. Copyright© 2017 by the Terasaki Research Institute.

  13. Interactions between the default network and dorsal attention network vary across default subsystems, time, and cognitive states.

    PubMed

    Dixon, Matthew L; Andrews-Hanna, Jessica R; Spreng, R Nathan; Irving, Zachary C; Mills, Caitlin; Girn, Manesh; Christoff, Kalina

    2017-02-15

    Anticorrelation between the default network (DN) and dorsal attention network (DAN) is thought to be an intrinsic aspect of functional brain organization reflecting competing functions. However, the effect size of functional connectivity (FC) between the DN and DAN has yet to be established. Furthermore, the stability of anticorrelations across distinct DN subsystems, different contexts, and time, remains unexplored. In study 1 we summarize effect sizes of DN-DAN FC from 20 studies, and in study 2 we probe the variability of DN-DAN interactions across six different cognitive states in a new data set. We show that: (i) the DN and DAN have an independent rather than anticorrelated relationship when global signal regression is not used (median effect size across studies: r=-.06; 95% CI: -.15 to .08); (ii) the DAN exhibits weak negative FC with the DN Core subsystem but is uncorrelated with the dorsomedial prefrontal and medial temporal lobe subsystems; (iii) DN-DAN interactions vary significantly across different cognitive states; (iv) DN-DAN FC fluctuates across time between periods of anticorrelation and periods of positive correlation; and (v) changes across time in the strength of DN-DAN coupling are coordinated with interactions involving the frontoparietal control network (FPCN). Overall, the observed weak effect sizes related to DN-DAN anticorrelation suggest the need to re-conceptualize the nature of interactions between these networks. Furthermore, our findings demonstrate that DN-DAN interactions are not stable, but rather, exhibit substantial variability across time and context, and are coordinated with broader network dynamics involving the FPCN. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. High performance lignin-acrylonitrile polymer blend materials

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

    Naskar, Amit K.; Tran, Chau D.

    A polymer blend material comprising: (i) a lignin component having a weight-average molecular weight of up to 1,000,000 g/mol; and (ii) an acrylonitrile-containing copolymer rubber component comprising acrylonitrile units in combination with diene monomer units, and having an acrylonitrile content of at least 20 mol %; wherein said lignin component is present in an amount of at least 5 wt % and up to about 95 wt % by total weight of components (i) and (ii); and said polymer blend material possesses a tensile yield stress of at least 5 MPa, or a tensile stress of at least 5 MPamore » at 10% elongation, or a tensile stress of at least 5 MPa at 100% elongation. Methods for producing the polymer blend, molded forms thereof, and articles thereof, are also described.« less

  15. Inhibition of Akt/mTOR/p70S6K Signaling Activity With Huangkui Capsule Alleviates the Early Glomerular Pathological Changes in Diabetic Nephropathy.

    PubMed

    Wu, Wei; Hu, Wei; Han, Wen-Bei; Liu, Ying-Lu; Tu, Yue; Yang, Hai-Ming; Fang, Qi-Jun; Zhou, Mo-Yi; Wan, Zi-Yue; Tang, Ren-Mao; Tang, Hai-Tao; Wan, Yi-Gang

    2018-01-01

    Huangkui capsule (HKC), a Chinese modern patent medicine extracted from Abelmoschus manihot (L.) medic, has been widely applied to clinical therapy in the early diabetic nephropathy (DN) patients. However, it remains elusive whether HKC can ameliorate the inchoate glomerular injuries in hyperglycemia. Recently the activation of phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling and its downstream regulator, 70-kDa ribosomal protein S6 kinase (p70S6K), play important roles in the early glomerular pathological changes of DN including glomerular hypertrophy, glomerular basement membrane (GBM) thickening and mild mesangial expansion. This study thereby aimed to clarify therapeutic effects of HKC during the initial phase of DN and its underlying mechanisms. Fifteen rats were randomly divided into 3 groups: the normal group, the model group and the HKC group. The early DN model rats were induced by unilateral nephrectomy combined with intraperitoneal injection of streptozotocin, and administered with either HKC suspension or vehicle after modeling and for a period of 4 weeks. Changes in the incipient glomerular lesions-related parameters in urine and blood were analyzed. Kidneys were isolated for histomorphometry, immunohistochemistry, immunofluorescence and Western blotting (WB) at sacrifice. In vitro , murine mesangial cells (MCs) were used to investigate inhibitory actions of hyperoside (HYP), a bioactive component of HKC, on cellular hypertrophy-associated signaling pathway by WB, compared with rapamycin (RAP). For the early DN model rats, HKC ameliorated micro-urinary albumin, body weight and serum albumin, but had no significant effects on renal function and liver enzymes; HKC improved renal shape, kidney weight and kidney hypertrophy index; HKC attenuated glomerular hypertrophy, GBM thickening and mild mesangial expansion; HKC inhibited the phosphorylation of Akt, mTOR and p70S6K, and the protein over-expression of transforming growth factor-β1 in kidneys. In vitro , the phosphorylation of PI3K, Akt, mTOR and p70S6K in MCs induced by high-glucose was abrogated by treatment of HYP or RAP. On the whole, this study further demonstrated HKC safely and efficiently alleviates the early glomerular pathological changes of DN, likely by inhibiting Akt/mTOR/p70S6K signaling activity in vivo and in vitro , and provided the first evidence that HKC directly contributes to the prevention of the early DN.

  16. Renin Angiotensin Aldosterone System (RAAS): its biology and drug targets for treating diabetic nephropathy.

    PubMed

    Zain, Maryam; Awan, Fazli Rabbi

    2014-09-01

    Diabetes mellitus is a multifactorial disorder of hyperglycemia caused by a combination of biochemical, molecular and genetic factors, which leads to the dysfunction of various organs including kidneys. Diabetic nephropathy (DN) is one of the microvascular complications of diabetes that results due to poor glycemic control. Several molecular and biochemical pathways have been implicated in the pathogenesis of DN. Of these, the Renin Angiotensin Aldosterone System (RAAS) is considered as a key pathway. RAAS involves various subsystems which contribute to the development of DN. Mutations in several genes of the RAAS pathway have been associated with the development of DN. These genes or their products present them as therapeutic targets for potent drugs to control or prevent DN, and development of new drugs for targeting the RAAS. Drugs in use for DN are mainly the Angiotensin Converting Enzyme (ACE) inhibitors, Angiotensin Receptors Blockers (ARB) and renin inhibitors which play important roles in reducing DN. Hence, the present review is focused on the pathophysiology and genetic factors for DN by exploring the RAAS pathway and emphasizing the benefits of blocking this pathway to control and prevent DN.

  17. Change in biotypic diversity of Russian wheat aphid (Hemiptera: Aphididae) populations in the United States

    USDA-ARS?s Scientific Manuscript database

    A key component of Russian wheat aphid (RWA), Diuraphis noxia (Kurdjumov), management has been through planting resistant wheat cultivars. A new biotype, RWA2, appeared in 2003 which caused widespread damage to wheat cultivars containing Dn4 gene. Biotypic diversity in RWA populations has not been...

  18. Matrix Gelatinases in Atherosclerosis and Diabetic Nephropathy: Progress and Challenges.

    PubMed

    Dimas, Grigorios G; Didangelos, Triantafyllos P; Grekas, Dimitrios M

    2017-01-01

    Matrix metalloproteinases (MMPs) are zinc-dependent proteases that degrade components of the extracellular matrix (ECM). In glomerular disease, MMPs are major regulators of ECM degradation as well as structural and functional integrity in the glomerulus. In altered matrix composition diseases, glomerular damage is due to increased degradation of kidney and vessel basement membranes (BMs) by MMPs. MMP -2 and -9 are both considered as the main enzymes that degrade collagen type-IV (coll-IV), which represents the key collagenous component of ECM and constitutes the architectural structure of vessels and glomerular BM. There is growing evidence implicating MMPs in atherosclerosis as well as in cardiovascular disease (CVD) and chronic kidney disease (CKD). Specific endogenous tissue inhibitors of MMPs (TIMPs) are also implicated in CKD, CVD and diabetic nephropathy (DN). The present review discusses the role of MMPs -2 and -9 in DN, as a leading cause of endstage renal disease and as a model of the link between progressive glomerulosclerosis and MMP expression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response

    PubMed Central

    Klump, Georg M.; Tollin, Daniel J.

    2016-01-01

    The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

  20. A case-control study of apoA5 -1131T-->C polymorphism that examines the role of triglyceride levels in diabetic nephropathy.

    PubMed

    Baum, Larry; Ng, Maggie C Y; So, Wing-Yee; Poon, Emily; Wang, Ying; Lam, Vincent K L; Tomlinson, Brian; Chan, Juliana C N

    2007-01-01

    Patients with diabetic nephropathy (DN) have increased plasma fasting triglyceride (TG) levels, and most prospective studies report that elevated TG precedes DN. TG-rich lipoprotein particles might promote progression of DN. To test the hypothesis that elevated TG levels contribute to the development of DN, one may examine whether a polymorphism strongly associated with TG levels affects DN risk. The apolipoprotein A5 (apoA5) -1131T-->C polymorphism has a large effect on the TG level, and all three genotypes are relatively common in East Asians. Therefore, we sought to examine the association of this polymorphism with DN. We genotyped the apoA5 -1131T-->C polymorphism in a case-control study involving 367 Chinese Type 2 diabetes patients with DN and 382 without DN, as well as 198 subjects without diabetes. Mean fasting TG levels were higher in CC than in TT carriers by 41%, 54%, and 62% in each of the three subject groups, respectively. However, the genotype distributions did not differ between patients with and without nephropathy (P=.69). Therefore, these results weigh against the hypothesis that high fasting TG per se causes DN. The strong association between TG level and DN may be due to a factor that is usually closely linked to TG level but that is not affected by the apoA5 polymorphism.

  1. Stress Testing of Data-Communication Networks

    NASA Technical Reports Server (NTRS)

    Leucht, Kurt; Bedette, Guy

    2006-01-01

    NetStress is a computer program that stress-tests a data-communication network and components thereof. NetStress comprises two components running, respectively, in a transmitting system and a receiving system connected to a network under test

  2. 30 CFR 27.39 - Tests to determine resistance to vibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS METHANE-MONITORING SYSTEMS Test Requirements § 27.39 Tests to... to verify the reliability and durability of a methane-monitoring system or component(s) thereof where...

  3. Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group.

    PubMed

    de Wit, P E; van't Hof-Grootenboer, B; Ruiter, D J; Bondi, R; Bröcker, E B; Cesarini, J P; Hastrup, N; Hou-Jensen, K; MacKie, R M; Scheffer, E

    1993-01-01

    Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN. Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low. The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non-DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively. On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN.

  4. A single group, pretest-posttest clinical trial for the effects of dry needling on wrist flexors spasticity after stroke.

    PubMed

    Fakhari, Zahra; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Mansouri, Korosh; Radinmehr, Hojjat

    2017-01-01

    Spasticity is a common complication after stroke. Dry needling (DN) is suggested as a novel method for treatment of muscle spasticity. To explore the effects of DN on wrist flexors spasticity poststroke. A single group, pretest-posttest clinical trial was used. Twenty nine patients with stroke (16 male; mean age 54.3 years) were tested at baseline (T0), immediately after DN (T1), and one hour after DN (T2). DN was applied for flexor carpi radialis (FCR) and flexor carpi ulnaris on the affected arm for single session, one minute per muscle. The Modified Modified Ashworth Scale (MMAS), passive resistance force, wrist active and passive range of motion, Box and Block Test, and FCR H-reflex were outcome measures. Significant reductions in MMAS scores were seen both immediately after DN and at 1-hour follow-up (median 2 at T0 to 1 at T1 and T2). There were significant improvements in other measures between the baseline values at T0 and those recorded immediately after the DN at T1 or one hour later at T2. This study suggests that DN reduced wrist flexors spasticity and alpha motor neuron excitability in patients with stroke, and improvements persisted for one hour after DN.

  5. Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement.

    PubMed

    Kim, Caroline C; Swetter, Susan M; Curiel-Lewandrowski, Clara; Grichnik, James M; Grossman, Douglas; Halpern, Allan C; Kirkwood, John M; Leachman, Sancy A; Marghoob, Ashfaq A; Ming, Michael E; Nelson, Kelly C; Veledar, Emir; Venna, Suraj S; Chen, Suephy C

    2015-02-01

    The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence. To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins. The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed. A consensus statement by the PLS of the MPWG following review of the literature, group discussions, and a structured Delphi method consensus. This consensus statement reviews the complexities of management of CAN/DN. A review of the literature and 2 rounds of a structured Delphi consensus resulted in the following recommendations: (1) mildly and moderately DN with clear margins do not need to be reexcised, (2) mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than reexcised, and (3) observation may be a reasonable option for management of moderately DN with positive histologic margins without clinically apparent residual pigmentation; however, more data are needed to make definitive recommendations in this clinical scenario.

  6. Aerodynamic parameters of across-wind self-limiting vibration for square sections after lock-in in smooth flow

    NASA Astrophysics Data System (ADS)

    Wu, Jong-Cheng; Chang, Feng-Jung

    2011-08-01

    The paper aims to identify the across-wind aerodynamic parameters of two-dimensional square section structures after the lock-in stage from the response measurements of wind tunnel tests under smooth wind flow conditions. Firstly, a conceivable self-limiting model was selected from the existent literature and the revisit of the analytical solution shows that the aerodynamic parameters (linear and nonlinear aerodynamic dampings Y1 and ɛ, and aerodynamic stiffness Y2) are not only functions of the section shape and reduced wind velocity but also dependent on both the mass ratio ( mr) and structural damping ratio ( ξ) independently, rather than on the Scruton number as a whole. Secondly, the growth-to-resonance (GTR) method was adopted for identifying the aerodynamic parameters of four different square section models (DN1, DN2, DN3 and DN4) by varying the density ranging from 226 to 409 kg/m 3. To improve the accuracy of the results, numerical optimization of the curve-fitting for experimental and analytical response in time domain was performed to finalize the results. The experimental results of the across-wind self-limiting steady-state amplitudes after lock-in stage versus the reduced wind velocity show that, except the tail part of the DN1 case slightly decreases indicating a pure vortex-induced lock-in persists, the DN2, DN3 and DN4 cases have a trend of monotonically increasing with the reduced wind velocity, which shows an asymptotic combination with the galloping behavior. Due to such a combination effect, all three aerodynamic parameters decrease as the reduced wind velocity increases and asymptotically approaches to a constant at the high branch. In the DN1 case, the parameters Y1 and Y2 decrease as the reduced wind velocity increases while the parameter ɛ slightly reverses in the tail part. The 3-dimensional surface plot of the Y1, ɛ and Y2 curves further show that, excluding the DN1 case, the parameters in the DN2, DN3 and DN4 cases almost follow a symmetric concave-up distribution versus the density under the same reduced wind velocity. This indicates that the aerodynamic parameters in the DN3 case are the minima along the density distribution.

  7. Distribution and diversity of Russian wheat aphid (Hemiptera: Aphididae) biotypes in South Africa and Lesotho.

    PubMed

    Jankielsohn, Astrid

    2011-10-01

    Russian wheat aphid, Diuraphis noxia (Kurdjumov) (Hemiptera: Aphididae) was recorded for the first time in South Africa in 1978. In 2005, a second biotype, RWASA2, emerged, and here we report on the emergence of yet another biotype, found for the first time in 2009. The discovery of new Russian wheat aphid biotypes is a significant challenge to the wheat, Triticum aestivum L., industry in South Africa. Russian wheat aphid resistance in wheat, that offered wheat producers a long-term solution to Russian wheat aphid control, may no longer be effective in areas where the new biotypes occur. It is therefore critical to determine the diversity and extent of distribution of biotypes in South Africa to successfully deploy Russian wheat aphid resistance in wheat. Screening of 96 Russian wheat aphid clones resulted in identification of three Russian wheat aphid biotypes. Infestations of RWASA1 caused susceptible damage symptoms only in wheat entries containing the Dn3 gene. Infestations of RWASA2 caused susceptible damage symptoms in wheat entries containing Dn1, Dn2, Dn3, and Dn9 resistant genes. Based on the damage-rating scores for the seven resistance sources, a new biotype, which caused damage rating scores different from those for RWASA1 and RWASA2, was evident among the Russian wheat aphid populations tested. This new biotype is virulent to the same resistance sources as RWASA2 (Dn1, Dn2, Dn3, and Dn9), but it also has added virulence to Dn4, whereas RWASA2 is avirulent to this resistance source.

  8. The application of neuropathic pain questionnaires in burning mouth syndrome patients.

    PubMed

    Heo, Jun-Young; Ok, Soo-Min; Ahn, Yong-Woo; Ko, Myung-Yun; Jeong, Sung-Hee

    2015-01-01

    To evaluate and compare the validity of the PainDETECT, DN4, and abbreviated DN4 (DN4i) neuropathic pain questionnaires for primary burning mouth syndrome (BMS), which is a burning sensation in the oral mucosa in the absence of any identifiable organic etiology. Eighty-one patients (42 with primary BMS and 39 with nociceptive pain) complaining of a burning sensation and pain in their oral mucosa were enrolled in this study. All of the patients completed the neuropathic pain questionnaires. The sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic (ROC) curve were estimated. Then the relationship between pain intensity and total neuropathic pain score was investigated. Data were analyzed with the chi-square test and independent t test for subjects' baseline characteristic differences, and with Pearson correlation coefficients for the relationship of variables. The mean area under the ROC curves (AUCs) for PainDETECT, DN4, and DN4i were 0.81, 0.79, and 0.81, respectively. There was no statistically significant difference in the AUCs among the questionnaires. PainDETECT, DN4, and DN4i had a lower sensitivity and specificity for BMS compared to previous validation studies. The total scores for PainDETECT, DN4, and DN4i in the primary BMS group were significantly associated with pain intensity. Although the results of this study suggest that neuropathic pain questionnaires, such as PainDETECT and DN4, are not ideal principal screening tools for BMS patients, a substantial proportion of neuropathic symptoms in primary BMS patients were identified.

  9. The Role of Endoplasmic Reticulum Stress in Diabetic Nephropathy.

    PubMed

    Fan, Ying; Lee, Kyung; Wang, Niansong; He, John Cijiang

    2017-03-01

    Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a major role in the development and progression of DN. Recent findings suggested that many attributes of DN, such as hyperglycemia, proteinuria, and increased advanced glycation end products and free fatty acids, can all trigger unfolded protein response (UPR) in kidney cells. Herein, we review the current knowledge on the role of ER stress in the setting of kidney injury with a specific emphasis on DN. As maladaptive ER stress response caused by excessively prolonged UPR will eventually cause cell death and increase kidney injury, several ER stress inhibitors have been shown to improve DN in animal models, albeit blocking both adaptive and maladaptive UPR. More recently, reticulon-1A (RTN1A), an ER-associated protein, was shown to be increased in both human and mouse diabetic kidneys. Its expression correlates with the progression of DN, and its polymorphisms are associated with kidney disease in people with diabetes. Increased RTN1A expression heightened the ER stress response and renal cell apoptosis, and conversely reduced RTN1A in renal cells decreased apoptosis and ameliorated kidney injury and DN progression, suggesting that RTN1A may be a novel target to specifically restrain the maladaptive UPR. These findings suggest that ER stress response in renal cells is a key driver of progression of DN and that the inhibition of the unchecked ER stress response in DN, such as by inhibition of RTN1A function, may be a promising therapeutic approach against DN.

  10. Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy.

    PubMed

    Liu, Jingping; Wang, Chengshi; Liu, Fang; Lu, Yanrong; Cheng, Jingqiu

    2015-03-01

    Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by (1)H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN.

  11. Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria

    PubMed Central

    Jauregui, Alexandra; Mintz, Daniel H; Mundel, Peter; Fornoni, Alessia

    2010-01-01

    Purpose of review In diabetic nephropathy (DN), insulin resistance and hyperinsulinemia correlate with the development of albuminuria. The possibility that altered insulin signaling in glomerular cells and particularly podocytes contributes to the development of DN will be discussed. Recent findings While normal podocytes uptake glucose in response to insulin, diabetic podocytes become insulin resistant in experimental DN prior to the development of significant albuminuria. Both clinical and experimental data suggest that insulin sensitizers may be renoprotective independently of their systemic effects on the metabolic control of diabetes. Summary We will review the clinical and experimental evidence that altered insulin signaling correlates with the development of DN in both type 1 and type 2 diabetes, and that insulin sensitizers may be superior to other hypoglycemic agents in the prevention of DN. We will then review potential mechanisms by which altered podocyte insulin signaling may contribute to the development of DN. Understanding the role of podocyte in glucose metabolism is important because it may lead to the discovery of novel pathogenetic mechanisms of DN, it may affect current strategies for prevention and treatment of DN, and it may allow for the identification of novel therapeutic targets. PMID:19724224

  12. Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome

    PubMed Central

    Best, Tyler K.; Cramer, Nathan P.; Chakrabarti, Lina; Haydar, Tarik F.; Galdzicki, Zygmunt

    2013-01-01

    GABAergic dysfunction is implicated in hippocampal deficits of the Ts65Dn mouse model of Down syndrome (DS). Since Ts65Dn mice overexpress G-protein coupled inward-rectifying potassium (GIRK2) containing channels, we sought to evaluate whether increased GABAergic function disrupts the functioning of hippocampal circuitry. After confirming that GABAB/GIRK current density is significantly elevated in Ts65Dn CA1 pyramidal neurons, we compared monosynaptic inhibitory inputs in CA1 pyramidal neurons in response to proximal (stratum radiatum; SR) and distal (stratum lacunosum moleculare; SLM) stimulation of diploid and Ts65Dn acute hippocampal slices. Synaptic GABAB and GABAA mediated currents evoked by SR stimulation were generally unaffected in Ts65Dn CA1 neurons. However, the GABAB/GABAA ratios evoked by stimulation within the SLM of Ts65Dn hippocampus were significantly larger in magnitude, consistent with increased GABAB/GIRK currents after SLM stimulation. These results indicate that GIRK overexpression in Ts65Dn has functional consequences which affect the balance between GABAB and GABAA inhibition of CA1 pyramidal neurons, most likely in a pathway specific manner, and may contribute to cognitive deficits reported in these mice. PMID:22178330

  13. Validity and reliability of the Spanish version of the DN4 (Douleur Neuropathique 4 questions) questionnaire for differential diagnosis of pain syndromes associated to a neuropathic or somatic component

    PubMed Central

    Perez, Concepcion; Galvez, Rafael; Huelbes, Silvia; Insausti, Joaquin; Bouhassira, Didier; Diaz, Silvia; Rejas, Javier

    2007-01-01

    Background This study assesses the validity and reliability of the Spanish version of DN4 questionnaire as a tool for differential diagnosis of pain syndromes associated to a neuropathic (NP) or somatic component (non-neuropathic pain, NNP). Methods A study was conducted consisting of two phases: cultural adaptation into the Spanish language by means of conceptual equivalence, including forward and backward translations in duplicate and cognitive debriefing, and testing of psychometric properties in patients with NP (peripheral, central and mixed) and NNP. The analysis of psychometric properties included reliability (internal consistency, inter-rater agreement and test-retest reliability) and validity (ROC curve analysis, agreement with the reference diagnosis and determination of sensitivity, specificity, and positive and negative predictive values in different subsamples according to type of NP). Results A sample of 164 subjects (99 women, 60.4%; age: 60.4 ± 16.0 years), 94 (57.3%) with NP (36 with peripheral, 32 with central, and 26 with mixed pain) and 70 with NNP was enrolled. The questionnaire was reliable [Cronbach's alpha coefficient: 0.71, inter-rater agreement coefficient: 0.80 (0.71–0.89), and test-retest intra-class correlation coefficient: 0.95 (0.92–0.97)] and valid for a cut-off value ≥ 4 points, which was the best value to discriminate between NP and NNP subjects. Discussion This study, representing the first validation of the DN4 questionnaire into another language different than the original, not only supported its high discriminatory value for identification of neuropathic pain, but also provided supplemental psychometric validation (i.e. test-retest reliability, influence of educational level and pain intensity) and showed its validity in mixed pain syndromes. PMID:18053212

  14. Neurophysiological and clinical effects of dry needling in patients with upper trapezius myofascial trigger points.

    PubMed

    Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

    2017-01-01

    Dry needling (DN) is a widely used in treatment of myofascial trigger points (MTrPs). The purpose of this pretest-posttest clinical trial was to investigate the neurophysiological and clinical effects of DN in patients with MTrPs. A sample of 20 patients (3 man, 17 women; mean age 31.7 ± 10.8) with upper trapezius MTrPs received one session of deep DN. The outcomes of neuromuscular junction response (NMJR), sympathetic skin response (SSR), pain intensity (PI) and pressure pain threshold (PPT) were measured at baseline and immediately after DN. There were significant improvements in SSR latency and amplitude, pain, and PPT after DN. The NMJR decreased and returned to normal after DN. A single session of DN to the active upper trapezius MTrP was effective in improving pain, PPT, NMJR, and SSR in patients with myofascial trigger points. Further studies are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. β-Arrestins promote podocyte injury by inhibition of autophagy in diabetic nephropathy.

    PubMed

    Liu, J; Li, Q X; Wang, X J; Zhang, C; Duan, Y Q; Wang, Z Y; Zhang, Y; Yu, X; Li, N J; Sun, J P; Yi, F

    2016-04-07

    β-Arrestins are multifunctional proteins originally identified as negative adaptors of G protein-coupled receptors (GPCRs). Emerging evidence has also indicated that β-arrestins can activate signaling pathways independent of GPCR activation. This study was to elucidate the role of β-arrestins in diabetic nephropathy (DN) and hypothesized that β-arrestins contribute to diabetic renal injury by mediating podocyte autophagic process. We first found that both β-arrestin-1 and β-arrestin-2 were upregulated in the kidney from streptozotocin-induced diabetic mice, diabetic db/db mice and kidney biopsies from diabetic patients. We further revealed that either β-arrestin-1 or β-arrestin-2 deficiency (Arrb1(-/-) or Arrb2(-/-)) ameliorated renal injury in diabetic mice. In vitro, we observed that podocytes increased both β-arrestin-1 and β-arrestin-2 expression levels under hyperglycemia condition and further demonstrated that β-arrestin-1 and β-arrestin-2 shared common mechanisms to suppress podocyte autophagy by negative regulation of ATG12-ATG5 conjugation. Collectively, this study for the first time demonstrates that β-arrestin-1 and β-arrestin-2 mediate podocyte autophagic activity, indicating that β-arrestins are critical components of signal transduction pathways that link renal injury to reduce autophagy in DN. Modulation of these pathways may be an innovative therapeutic strategy for treating patients with DN.

  16. The mechanical properties and cytotoxicity of cell-laden double-network hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules.

    PubMed

    Shin, Hyeongho; Olsen, Bradley D; Khademhosseini, Ali

    2012-04-01

    A major goal in the application of hydrogels for tissue engineering scaffolds, especially for load-bearing tissues such as cartilage, is to develop hydrogels with high mechanical strength. In this study, a double-network (DN) strategy was used to engineer strong hydrogels that can encapsulate cells. We improved upon previously studied double-network (DN) hydrogels by using a processing condition compatible with cell survival. The DN hydrogels were created by a two-step photocrosslinking using gellan gum methacrylate (GGMA) for the rigid and brittle first network, and gelatin methacrylamide (GelMA) for the soft and ductile second network. We controlled the degree of methacrylation of each polymer so that they obtain relevant mechanical properties as each network. The DN was formed by photocrosslinking the GGMA, diffusing GelMA into the first network, and photocrosslinking the GelMA to form the second network. The formation of the DN was examined by diffusion tests of the large GelMA molecules into the GGMA network, the resulting enhancement in the mechanical properties, and the difference in mechanical properties between GGMA/GelMA single networks (SN) and DNs. The resulting DN hydrogels exhibited the compressive failure stress of up to 6.9 MPa, which approaches the strength of cartilage. It was found that there is an optimal range of the crosslink density of the second network for high strength of DN hydrogels. DN hydrogels with a higher mass ratio of GelMA to GGMA exhibited higher strength, which shows promise in developing even stronger DN hydrogels in the future. Three dimensional (3D) encapsulation of NIH-3T3 fibroblasts and the following viability test showed the cell-compatibility of the DN formation process. Given the high strength and the ability to encapsulate cells, the DN hydrogels made from photocrosslinkable macromolecules could be useful for the regeneration of load-bearing tissues. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. The mechanical properties and cytotoxicity of cell-laden double-network hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules

    PubMed Central

    Shin, Hyeongho; Olsen, Bradley D.; Khademhosseini, Ali

    2012-01-01

    A major goal in the application of hydrogels for tissue engineering scaffolds, especially for load-bearing tissues such as cartilage, is to develop hydrogels with high mechanical strength. In this study, a double-network (DN) strategy was used to engineer strong hydrogels that can encapsulate cells. We improved upon previously studied double-network (DN) hydrogels by using a processing condition compatible with cell survival. The DN hydrogels were created by a two-step photocrosslinking using gellan gum methacrylate (GGMA) for the rigid and brittle first network, and gelatin methacrylamide (GelMA) for the soft and ductile second network. We controlled the degree of methacrylation of each polymer so that they obtain relevant mechanical properties as each network. The DN was formed by photocrosslinking the GGMA, diffusing GelMA into the first network, and photocrosslinking the GelMA to form the second network. The formation of the DN was examined by diffusion tests of the large GelMA molecules into the GGMA network, the resulting enhancement in the mechanical properties, and the difference in mechanical properties between GGMA/GelMA single networks (SN) and DNs. The resulting DN hydrogels exhibited the compressive failure stress of up to 6.9 MPa, which approaches the strength of cartilage. It was found that there is an optimal range of the crosslink density of the second network for high strength of DN hydrogels. DN hydrogels with a higher mass ratio of GelMA to GGMA exhibited higher strength, which shows promise in developing even stronger DN hydrogels in the future. Three dimensional (3D) encapsulation of NIH-3T3 fibroblasts and the following viability test showed the cell-compatibility of the DN formation process. Given the high strength and the ability to encapsulate cells, the DN hydrogels made from photocrosslinkable macromolecules could be useful for the regeneration of load-bearing tissues. PMID:22265786

  18. The relationship between hemoglobin level and the type 1 diabetic nephropathy in Anhui Han's patients.

    PubMed

    Jiang, Jun; Lei, Lan; Zhou, Xiaowan; Li, Peng; Wei, Ren

    2018-02-20

    Recent studies have shown that low hemoglobin (Hb) level promote the progression of chronic kidney disease. This study assessed the relationship between Hb level and type 1 diabetic nephropathy (DN) in Anhui Han's patients. There were a total of 236 patients diagnosed with type 1 diabetes mellitus and (T1DM) seen between January 2014 and December 2016 in our centre. Hemoglobin levels in patients with DN were compared with those without DN. The relationship between Hb level and the urinary albumin-creatinine ratio (ACR) was examined by Spearman's correlational analysis and multiple stepwise regression analysis. The binary logistic multivariate regression analysis was performed to analyze the correlated factors for type 1 DN, calculate the Odds Ratio (OR) and 95%confidence interval (CI). The predicting value of Hb level for DN was evaluated by area under receiver operation characteristic curve (AUROC) for discrimination and Hosmer-Lemeshow goodness-of-fit test for calibration. The average Hb levels in the DN group (116.1 ± 20.8 g/L) were significantly lower than the non-DN group (131.9 ± 14.4 g/L) , P < 0.001. Hb levels were independently correlated with the urinary ACR in multiple stepwise regression analysis. The logistic multivariate regression analysis showed that the Hb level (OR: 0.936, 95% CI: 0.910 to 0.963, P < 0.001) was inversely correlated with DN in patients with T1DM. In sub-analysis, low Hb level (Hb < 120g/L in female, Hb < 130g/L in male) was still negatively associated with DN in patients with T1DM. The AUROC was 0.721 (95% CI: 0.655 to 0.787) in assessing the discrimination of the Hb level for DN. The value of P was 0.593 in Hosmer-Lemeshow goodness-of-fit test. In Anhui Han's patients with T1DM, the Hb level is inversely correlated with urinary ACR and DN. This article is protected by copyright. All rights reserved.

  19. The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

    PubMed

    Zhuang, Langen; Li, Ming; Yu, Changhua; Li, Can; Zhao, Mingming; Lu, Ming; Zheng, Taishan; Zhang, Rong; Zhao, Weijing; Bao, Yuqian; Xiang, Kunsan; Jia, Weiping; Wang, Niansong; Liu, Limei

    2014-02-01

    The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p < 0.05). Leu/Met and Met/Met type 2 diabetics had significantly lower AER and Scr levels and higher eGFR level than Leu/Leu type 2 diabetics (all p < 0.001). The GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

  20. Protein S Protects against Podocyte Injury in Diabetic Nephropathy.

    PubMed

    Zhong, Fang; Chen, Haibing; Xie, Yifan; Azeloglu, Evren U; Wei, Chengguo; Zhang, Weijia; Li, Zhengzhe; Chuang, Peter Y; Jim, Belinda; Li, Hong; Elmastour, Firas; Riyad, Jalish M; Weber, Thomas; Chen, Hongyu; Wang, Yongjun; Zhang, Aihua; Jia, Weiping; Lee, Kyung; He, John C

    2018-05-01

    Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN. Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose-induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose- and TNF- α -induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice. Conclusions Our results support a protective role of PS against glomerular injury in DN progression. Copyright © 2018 by the American Society of Nephrology.

  1. Single-Dose Pharmacokinetic Study of Tramadol Extended-Release Tablets in Children and Adolescents.

    PubMed

    Vandenbossche, Joris; Van Peer, Achiel; Richards, Henry

    2016-09-01

    Combined analyses from 2 open-label, phase-1 studies-the pharmacokinetic profile of tramadol and its metabolite (M1) following a single oral dose of tramadol extended release (ER) (25 to 100 mg) in children (7 to 11 years old; study 1: n = 37) and adolescents (12 to 17 years old; study 2: n = 38) with painful conditions-were historically compared with that of healthy adults following similar dosing. The dose-normalized area under the curve (DN AUC0-24h ) and maximum concentration (DN Cmax ) of tramadol and of M1 in children and in adolescents were lower than those in adults (children vs adults: tramadol, DN AUC0-24h 82.19%; DN Cmax 80.38%, P = .0031; M1, DN AUC0-24h 51.19%, DN Cmax 52.68%, P < .0001; adolescents vs adults: tramadol, DN AUC0-24h 89.56%, DN Cmax 84.01%; M1, DN AUC0-24h 85.28%, DN Cmax 83.03%, P = .0004). The arithmetic mean terminal elimination t1/2 of tramadol in children and adolescents was comparable to that in adults (children 8.4 hours; adolescents 8.5 hours; adults 7.9 hours). The most frequently reported (≥5% of participants) treatment-emergent adverse events in children included headache, upper abdominal pain and constipation, and in adolescents were headache, nausea, dizziness, and stomach discomfort. Multiple factors may have contributed to these observations, including a higher proportion of children (56%) who may have a lower activity of CYP2D6, resulting in reduced clearance of tramadol. © 2016, The American College of Clinical Pharmacology.

  2. Encyclopedia of software components

    NASA Technical Reports Server (NTRS)

    Vanwarren, Lloyd (Inventor); Beckman, Brian C. (Inventor)

    1991-01-01

    Intelligent browsing through a collection of reusable software components is facilitated with a computer having a video monitor and a user input interface such as a keyboard or a mouse for transmitting user selections, by presenting a picture of encyclopedia volumes with respective visible labels referring to types of software, in accordance with a metaphor in which each volume includes a page having a list of general topics under the software type of the volume and pages having lists of software components for each one of the generic topics, altering the picture to open one of the volumes in response to an initial user selection specifying the one volume to display on the monitor a picture of the page thereof having the list of general topics and altering the picture to display the page thereof having a list of software components under one of the general topics in response to a next user selection specifying the one general topic, and then presenting a picture of a set of different informative plates depicting different types of information about one of the software components in response to a further user selection specifying the one component.

  3. Encyclopedia of Software Components

    NASA Technical Reports Server (NTRS)

    Warren, Lloyd V. (Inventor); Beckman, Brian C. (Inventor)

    1997-01-01

    Intelligent browsing through a collection of reusable software components is facilitated with a computer having a video monitor and a user input interface such as a keyboard or a mouse for transmitting user selections, by presenting a picture of encyclopedia volumes with respective visible labels referring to types of software, in accordance with a metaphor in which each volume includes a page having a list of general topics under the software type of the volume and pages having lists of software components for each one of the generic topics, altering the picture to open one of the volumes in response to an initial user selection specifying the one volume to display on the monitor a picture of the page thereof having the list of general topics and altering the picture to display the page thereof having a list of software components under one of the general topics in response to a next user selection specifying the one general topic, and then presenting a picture of a set of different informative plates depicting different types of information about one of the software components in response to a further user selection specifying the one component.

  4. Immediate and short-term effects of the combination of dry needling and percutaneous TENS on post-needling soreness in patients with chronic myofascial neck pain

    PubMed Central

    León-Hernández, Jose V.; Martín-Pintado-Zugasti, Aitor; Frutos, Laura G.; Alguacil-Diego, Isabel M.; de la Llave-Rincón, Ana I.; Fernandez-Carnero, Josue

    2016-01-01

    ABSTRACT Background Dry needling (DN) and percutaneous electrical nerve stimulation (PENS) are widely used techniques in the treatment of myofascial pain. Objective To investigate the immediate and short-term effects of the combination of DN and PENS compared to DN alone on the upper trapezius muscle. Method This is a 72-hour follow-up single-blinded randomized controlled trial. Sixty-two volunteer patients with chronic myofascial neck pain with active Myofascial Trigger Points (MTrPs) in the upper trapezius muscle were recruited. Randomization was performed, and 31 patients received DN treatment (DN group) and 31 received DN and PENS (DN+PENS group). The primary outcomes were neck disability index (NDI) and visual analog scale for pain for both post-needling soreness (PNS) and neck pain intensity (NPI). Pressure pain threshold (PPT) and cervical range of motion (CROM) were the secondary outcomes. Results We detected between-group differences in NPI and PNS in favor of the DN+PENS group immediately after treatment. No between-group differences in NDI were observed. Conclusion PENS application after dry needling treatment is more effective than dry needling alone for decreasing soreness in the short term and improving neck pain intensity immediately in patients with myofascial chronic neck pain. PMID:27410163

  5. Emerging therapeutics for the treatment of diabetic nephropathy.

    PubMed

    Brenneman, Jehrod; Hill, Jon; Pullen, Steve

    2016-09-15

    Diabetic nephropathy (DN) is the most common pathology contributing to the development of chronic kidney disease (CKD). DN caused by hypertension and unmitigated inflammation in diabetics, renders the kidneys unable to perform normally, and leads to renal fibrosis and organ failure. The increasing global prevalence of DN has been directly attributed to rising incidences of Type II diabetes, and is now the largest non-communicable cause of death worldwide. Despite the high morbidity, successful new treatments for DN are lacking. This review seeks to provide new insight on emerging clinical candidates under investigation for the treatment of DN. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 78 FR 34132 - Certain Portable Electronic Communications Devices, Including Mobile Phones and Components...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-06

    ... INTERNATIONAL TRADE COMMISSION [Docket No 2958] Certain Portable Electronic Communications Devices, Including Mobile Phones and Components Thereof; Correction to Notice of Receipt of Complaint; Solicitation... of complaint entitled Certain Portable Electronic Communications Devices, Including Mobile Phones and...

  7. Anti-inflammatory effects of 4′-demethylnobiletin, a major metabolite of nobiletin

    PubMed Central

    Rakariyatham, Kanyasiri; Zheng, Jinkai; Guo, Shanshan; Tang, Zhonghai; Zhou, Shuangde; Xiao, Hang

    2015-01-01

    Nobiletin, a citrus flavonoid has been associated with various beneficial biological activities. 4′-Demethylnobiletin (4DN) is a major metabolite of nobiletin and its tissue level was found to be much higher than that of nobiletin after oral administration of nobiletin in mice. Anti-inflammatory effects of 4DN were studied in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. The results showed 4DN not only dose-dependently inhibited LPS-induced nitric oxide production, but also significantly reduced expression of pro-inflammatory mediators, namely PGE2, IL-1β and IL-6. 4DN potently suppressed the expression of iNOS and COX-2 at both protein and mRNA levels. 4DN also inhibited nuclear translocation of NF-κB and AP-1. Furthermore, we demonstrated that 4DN activated transcription factor Nrf2 and its dependent genes including HO-1 and NQO1 whose expression may contribute to anti-inflammatory effects. The results demonstrated anti-inflammatory effects of 4DN and provided a scientific basis for using nobiletin as a nutraceutical to inhibit inflammation–driven diseases. PMID:26770275

  8. RESONEUT: A detector system for spectroscopy with (d,n) reactions in inverse kinematics

    NASA Astrophysics Data System (ADS)

    Baby, L. T.; Kuvin, S. A.; Wiedenhöver, I.; Anastasiou, M.; Caussyn, D.; Colbert, K.; Quails, N.; Gay, D.

    2018-01-01

    The RESONEUT detector setup is described, which was developed for resonance spectroscopy using (d,n) reactions with radioactive beams in inverse kinematics and at energies around the Coulomb barrier. The goal of experiments with this setup is to determine the spectrum and proton-transfer strengths of the low-lying resonances, which have an impact on astrophysical reaction rates. The setup is optimized for l = 0 proton transfers in inverse kinematics, for which most neutrons are emitted at backward angles with energies in the 80-300 keV range. The detector system is comprised of 9 p-terphenyl scintillators as neutron detectors, two annular silicon-strip detectors for light charged particles, one position-resolving gas ionization chamber for heavy ion detection, and a barrel of NaI-detectors for the detection of γ-rays. The detector commissioning and performance characteristics are described with an emphasis on the neutron-detector components.

  9. Diabetic nephropathy and antioxidants.

    PubMed

    Tavafi, Majid

    2013-01-01

    Oxidative stress has crucial role in pathogenesis of diabetic nephropathy (DN). Despite satisfactory results from antioxidant therapy in rodent, antioxidant therapy showed conflicting results in combat with DN in diabetic patients. Directory of Open Access Journals (DOAJ), Google Scholar,Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Treatment of DN in human are insufficient with rennin angiotensin system (RAS) blockers, so additional agent ought to combine with this management. Meanwhile based on DN pathogenesis and evidences in experimental and human researches, the antioxidants are the best candidate. New multi-property antioxidants may be improved human DN that show high power antioxidant capacity, long half-life time, high permeability to mitochondrion, improve body antioxidants enzymes activity and anti-inflammatory effects. Based on this review and our studies on diabetic rats, rosmarinic acid a multi-property antioxidant may be useful in DN patients, but of course, needs to be proven in clinical trials studies.

  10. Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy

    PubMed Central

    TIAN, XIAO-QIN; ZHAO, LI-MIN; GE, JIA-PU; ZHANG, YAN; XU, YAN-CHENG

    2014-01-01

    Improving the early prediction and detection of diabetic nephropathy (DN) remains a great challenge in disease management. The aim of this study was to evaluate the early detection power of urinary vitamin D-binding protein (VDBP) for the diagnosis of DN. Urine samples were obtained from 45 healthy volunteers and 105 diabetic patients with normoalbuminuria (DM group), microalbuminuria (DN1 group) and macroalbuminuria (DN2 group) (n=35 per group). The VDBP expression patterns in urine from patients and controls were quantified by western blot analysis. The excretion levels of urinary VDBP were quantified with enzyme-linked immunosorbent assay. The quantification results were obtained by correcting for creatinine expression and showed that urinary VDBP levels were significantly elevated in the patients of the DN1 and DN2 groups compared with those of the DM group and normal controls (1,011.33±325.30 and 1,406.34±239.66 compared with 466.54±213.63 and 125.48±98.27 ng/mg, respectively) (P<0.001). Receiver operating characteristic analysis of urinary VDBP levels for the diagnosis of DN rendered an optimum cut-off value of 552.243 ng/mg corresponding to 92.86% sensitivity and 85.00% specificity, which also showed an area under the ROC curve of 0.966. In conclusion, the findings of the present study suggest that urinary VDBP may be a potential biomarker for the early detection and prevention of DN. Further studies are required to examine the pathogenic mechanisms of elevated VDBP levels and their role in the diagnosis of DN. PMID:24396416

  11. Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy.

    PubMed

    Ren, Feifeng; Tang, Lin; Cai, Yin; Yuan, Xin; Huang, Wenhan; Luo, Lei; Zhou, Jun; Zheng, Yaning

    2015-05-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria in diabetic nephropathy (DN). Some studies have suggested that dual blockade of the renin-angiotensin system provides additive benefits in DN but others showed increased adverse events. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy for DN. Studies were identified by searching MEDLINE, EMBASE, PubMed, and CNKI. All trials involved ACEI + ARB (combination therapy), and ACEI or ARB alone (monotherapy) for DN. The outcomes measured were urinary total proteinuria (UTP), urinary albumin excretion rate (UAER), serum creatinine, glomerular filtration rate (GFR), end-stage renal disease (ESRD), hyperkalemia, hypotension, and acute kidney injury (AKI). In the 32 included trials, 2596 patients received combination therapy and 3947 received monotherapy. UTP and UAER were significantly reduced by combined treatment compared with monotherapy. It was notable that low doses of combination therapy reduced UTP more than high doses. Serum creatinine, GFR, and ESRD were not significantly different between the two groups. In severe DN, the occurrence of hyperkalemia and AKI were higher with combination therapy. However, in mild DN, the prevalence of hyperkalemia and AKI were the same in both the groups. In mild DN, the occurrence of hypotension was higher with combination therapy; however, in severe DN, it was not different between the two groups. Our meta-analysis suggests that combination therapy can be used on DN with proteinuria, but should be used with caution in those with decreased renal function, especially with severe renal failure.

  12. Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome

    PubMed Central

    Scott-McKean, Jonah J.; Roque, Adriano L.; Surewicz, Krystyna; Johnson, Mark W.; Surewicz, Witold K.

    2018-01-01

    The Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compared with euploid mouse-derived slices. Additionally, therapeutically relevant doses of the drug memantine were shown to rescue learning and memory deficits in Ts65Dn mice. Here, we observed that 1 μM memantine had no detectable effect on HFS-induced LTP in either Ts65Dn- or control-derived slices, but it rescued TBS-induced LTP in Ts65Dn-derived slices to control euploid levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 μM picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices. PMID:29849573

  13. Method and apparatus for suppressing regenerative instability and related chatter in machine tools

    DOEpatents

    Segalman, Daniel J.; Redmond, James M.

    2001-01-01

    Methods of and apparatuses for mitigating chatter vibrations in machine tools or components thereof. Chatter therein is suppressed by periodically or continuously varying the stiffness of the cutting tool (or some component of the cutting tool), and hence the resonant frequency of the cutting tool (or some component thereof). The varying of resonant frequency of the cutting tool can be accomplished by modulating the stiffness of the cutting tool, the cutting tool holder, or any other component of the support for the cutting tool. By periodically altering the impedance of the cutting tool assembly, chatter is mitigated. In one embodiment, a cyclic electric (or magnetic) field is applied to the spindle quill which contains an electro-rheological (or magneto-rheological) fluid. The variable yield stress in the fluid affects the coupling of the spindle to the machine tool structure, changing the natural frequency of oscillation. Altering the modal characteristics in this fashion disrupts the modulation of current tool vibrations with previous tool vibrations recorded on the workpiece surface.

  14. Method and apparatus for suppressing regenerative instability and related chatter in machine tools

    DOEpatents

    Segalman, Daniel J.; Redmond, James M.

    1999-01-01

    Methods of and apparatuses for mitigating chatter vibrations in machine tools or components thereof. Chatter therein is suppressed by periodically or continuously varying the stiffness of the cutting tool (or some component of the cutting tool), and hence the resonant frequency of the cutting tool (or some component thereof). The varying of resonant frequency of the cutting tool can be accomplished by modulating the stiffness of the cutting tool, the cutting tool holder, or any other component of the support for the cutting tool. By periodically altering the impedance of the cutting tool assembly, chatter is mitigated. In one embodiment, a cyclic electric (or magnetic) field is applied to the spindle quill which contains an electro-rheological (or magneto-rheological) fluid. The variable yield stress in the fluid affects the coupling of the spindle to the machine tool structure, changing the natural frequency of oscillation. Altering the modal characteristics in this fashion disrupts the modulation of current tool vibrations with previous tool vibrations recorded on the workpiece surface.

  15. Modulation of gut microbiota and increase in fecal water content in mice induced by administration of Lactobacillus kefiranofaciens DN1.

    PubMed

    Jeong, Dana; Kim, Dong-Hyeon; Kang, Il-Byeong; Kim, Hyunsook; Song, Kwang-Young; Kim, Hong-Seok; Seo, Kun-Ho

    2017-02-22

    Lactobacillus kefiranofaciens is the key probiotic bacterium in kefir. In this study, we investigated the effects of oral consumption of L. kefiranofaciens on the fecal quality and intestinal microbiota of mice. Four-week-old Balb/c mice were divided into two groups (n = 8 each) and administered 0.2 mL of saline (control group) or saline containing 2 × 10 8 cfu L. kefiranofaciens DN1 (LKF_DN1 group) for two weeks. At the end of the experiment, their fecal samples were collected and the fecal quality and microbiota were assessed. The LKF_DN1 group exhibited higher total fecal weight and fecal weight per stool sample than the control group (p < 0.05). Interestingly, the fecal water content was significantly higher in the fecal samples of the LKF_DN1 group than in those of the control group (p < 0.05). The numbers of total bacteria, Firmicutes, Bacteroidetes, Lactobacillus, and Prevotella were significantly higher in the LKF_DN1 group than in the control group (p < 0.05). In contrast, the number of opportunistic pathogens, including Proteobacteria and Enterobacteriaceae, and the percentage of genus Clostridium among the total bacteria were significantly reduced in the LKF_DN1 group (p < 0.05). Our data suggest that regular L. kefiranofaciens DN1 administration could alleviate constipation and improve gut microbiota.

  16. Beneficial effects of β-conglycinin on renal function and nephrin expression in early streptozotocin-induced diabetic nephropathy rats.

    PubMed

    Yang, Hsin-Yi; Wu, Lin-Yi; Yeh, Wan-Ju; Chen, Jiun-Rong

    2014-01-14

    The objective of the present study was to investigate the effects of β-conglycinin and soya isoflavones on diabetic nephropathy (DN). DN was induced by an intravenous injection of streptozotocin (25 mg/kg) in spontaneously hypertensive rats. DN rats were divided into a non-diabetic group (C, control group) and three DN groups (D, DN with control diet; B, DN+control diet with one-eighth of casein replaced by β-conglycinin as the protein source; and I, DN+control diet with 0·01 % soya isoflavones). After a 4-week experimental period, we found that fasting blood sugar and plasma and kidney advanced glycation end product levels and 24 h urinary protein excretion of the B group were significantly lower than those of the D group and insulin sensitivity and nephrin expression of the B group were significantly higher than those of the D group. In addition, systolic blood pressure, angiotensin-converting enzyme activity, angiotensin II level and plasma TAG level of the B group were significantly lower than those of the D group, whereas only the levels of plasma TAG and thiobarbituric acid-reactive substances of the I group were lower than those of the D group. In conclusion, β-conglycinin may be beneficial for retarding DN progression and this effect cannot be completely explained by its isoflavone content.

  17. Diffusion barriers in modified air brazes

    DOEpatents

    Weil, Kenneth Scott; Hardy, John S; Kim, Jin Yong; Choi, Jung-Pyung

    2013-04-23

    A method for joining two ceramic parts, or a ceramic part and a metal part, and the joint formed thereby. The method provides two or more parts, a braze consisting of a mixture of copper oxide and silver, a diffusion barrier, and then heats the braze for a time and at a temperature sufficient to form the braze into a bond holding the two or more parts together. The diffusion barrier is an oxidizable metal that forms either a homogeneous component of the braze, a heterogeneous component of the braze, a separate layer bordering the braze, or combinations thereof. The oxidizable metal is selected from the group Al, Mg, Cr, Si, Ni, Co, Mn, Ti, Zr, Hf, Pt, Pd, Au, lanthanides, and combinations thereof.

  18. Diffusion barriers in modified air brazes

    DOEpatents

    Weil, Kenneth Scott [Richland, WA; Hardy, John S [Richland, WA; Kim, Jin Yong [Richland, WA; Choi, Jung-Pyung [Richland, WA

    2010-04-06

    A method for joining two ceramic parts, or a ceramic part and a metal part, and the joint formed thereby. The method provides two or more parts, a braze consisting of a mixture of copper oxide and silver, a diffusion barrier, and then heats the braze for a time and at a temperature sufficient to form the braze into a bond holding the two or more parts together. The diffusion barrier is an oxidizable metal that forms either a homogeneous component of the braze, a heterogeneous component of the braze, a separate layer bordering the braze, or combinations thereof. The oxidizable metal is selected from the group Al, Mg, Cr, Si, Ni, Co, Mn, Ti, Zr, Hf, Pt, Pd, Au, lanthanides, and combinations thereof.

  19. Predictive value of interleukin-10 promoter genotypes and haplotypes in determining the susceptibility to nephropathy in type 2 diabetes patients.

    PubMed

    Mtiraoui, Nabil; Ezzidi, Intissar; Kacem, Maha; Ben Hadj Mohamed, Manel; Chaieb, Molka; Haj Jilani, Aoutef Bel; Mahjoub, Touhami; Almawi, Wassim Y

    2009-01-01

    The IL-10 promoter polymorphisms -1082G/A, -819C/T, and -592C/A have been consistently associated with type 2 diabetes (T2DM). We examined whether these polymorphisms variants are also associated with progression of diabetic nephropathy (DN). These promoter variants were genotyped in 917 T2DM patients comprising 515 DN patients and 402 control patients without nephropathy (DWN), together with 748 non-diabetic control subjects. Haplotype analysis and multivariate regression analysis were employed in assessing the contribution of IL-10 haplotypes to DN risk, using genotype, clinical and biochemical profile, and their interactions as predictors of DN. Carriers of mutant -592A and -819T alleles, and -819T/T, -592A/A, and -819C/T genotypes were more frequent in T2DM. However, the -819C/T genotype appeared to be protective of DN, since lower frequency -819T allele and -819C/T genotype were seen in DN patients. Regression analysis identified -1082G/-819T/-592A (GTA) and -1082G/-819T/-592C (GTC) haplotypes as DN-protective haplotypes. Relative to the -1082G/-819C/-592C haplotype, GTA [P = 0.044; odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.30-0.98] and GTC (P = 0.045; OR = 0.56, 95% CI: 0.31-0.99) haplotypes were associated with decreased odds ratio (OR) for DN, after controlling for a number of covariates (age, sex, body mass index (BMI), hypertension, glucose, HbA(1c), DN duration, total cholesterol). Our results indicate that genetic variations at the IL-10 promoter influence the risk of nephropathy in T2DM patients and thus represent a potential DN genetic-susceptibility locus worthy of replication. Copyright 2009 John Wiley & Sons, Ltd.

  20. Identification of specific angiotensin-converting enzyme variants and haplotypes that confer risk and protection against type 2 diabetic nephropathy.

    PubMed

    Ezzidi, Intissar; Mtiraoui, Nabil; Kacem, Maha; Chaieb, Molka; Mahjoub, Touhami; Almawi, Wassim Y

    2009-11-01

    Cross-sectional and family studies identified angiotensin-converting enzyme (ACE) gene as a risk factor for diabetic nephropathy (DN). The contribution of ACE gene variants to DN development and progression is controversial and varies among different ethnic/racial groups. We investigated the association of three ACE gene variants with DN, rs1799752 insertion/deletion (I/D), rs1800764T/C and rs12449782A/G in 917 Tunisian type 2 diabetic (T2DM) patients: 515 with (DN) and 402 without (DWN) nephropathy. ACE genotyping was done by PCR-based assays; haplotype estimation was performed using H-Plus software (chi(2)-test based). Genotype frequency distributions of the three studied variants were in Hardy-Weinberg equilibrium. Minor allele frequency of rs1800764 was higher in DN patients than DWN patients or healthy controls, and minor allele frequency of rs1799752 was higher in DN than DWN patients. Higher frequency of rs1799752 and rs1800764 homozygous mutant genotypes was seen in DN compared to DWN patients. Of the three variants, only rs1799752 deletion/deletion (D/D) genotype was associated with a significant increase in albumin to creatinine ratios levels, and D/D carriers had elevated low-density lipoprotein, total cholesterol and urea. Three locus haplotype [rs1799752(I/D)/rs1800764(T/C)/rs12449782(A/G)] analysis revealed that the frequency of DCG haplotype was higher, while that of ITG and ICA haplotypes were lower among unselected type 2 diabetic patients. Taking ITA haplotype as reference, multivariate regression analysis confirmed the negative (ITG), and positive (DCG, DTG, DCA and DTA) association of specific ACE haplotypes with DN, after adjusting for potential nephropathy-linked covariates. Our results support the involvement of specific ACE variants in DN pathogenesis and demonstrate the presence of DN-specific haplotypes at the ACE locus.

  1. Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30.

    PubMed

    Perk, Lars R; Stigter-van Walsum, Marijke; Visser, Gerard W M; Kloet, Reina W; Vosjan, Maria J W D; Leemans, C René; Giaccone, Giuseppe; Albano, Raffaella; Comoglio, Paolo M; van Dongen, Guus A M S

    2008-10-01

    Targeting the c-Met receptor with monoclonal antibodies (MAbs) is an appealing approach for cancer diagnosis and treatment because this receptor plays a prominent role in tumour invasion and metastasis. Positron emission tomography (PET) might be a powerful tool for guidance of therapy with anti-Met MAbs like the recently described MAb DN30 because it allows accurate quantitative imaging of tumour targeting (immuno-PET). We considered the potential of PET with either (89)Zr-labelled (residualising radionuclide) or (124)I-labelled (non-residualising radionuclide) DN30 for imaging of Met-expressing tumours. The biodistribution of co-injected (89)Zr-DN30 and iodine-labelled DN30 was compared in nude mice bearing either the human gastric cancer line GLT-16 (high Met expression) or the head-and-neck cancer line FaDu (low Met expression). PET images were acquired in both xenograft models up to 4 days post-injection (p.i.) and used for quantification of tumour uptake. Biodistribution studies in GTL-16-tumour-bearing mice revealed that (89)Zr-DN30 achieved much higher tumour uptake levels than iodine-labelled DN30 (e.g. 19.6%ID/g vs 5.3%ID/g, 5 days p.i.), while blood levels were similar, indicating internalisation of DN30. Therefore, (89)Zr-DN30 was selected for PET imaging of GLT-16-bearing mice. Tumours as small as 11 mg were readily visualised with immuno-PET. A distinctive lower (89)Zr uptake was observed in FaDu compared to GTL-16 xenografts (e.g. 7.8%ID/g vs 18.1%ID/g, 3 days p.i.). Nevertheless, FaDu xenografts were also clearly visualised with (89)Zr-DN30 immuno-PET. An excellent correlation was found between PET-image-derived (89)Zr tumour uptake and ex-vivo-assessed (89)Zr tumour uptake (R(2)=0.98). The long-lived positron emitter (89)Zr seems attractive for PET-guided development of therapeutic anti-c-Met MAbs.

  2. Genetic, epigenetic and protein analyses of intercellular adhesion molecule 1 in Malaysian subjects with type 2 diabetes and diabetic nephropathy.

    PubMed

    Abu Seman, Norhashimah; Anderstam, Björn; Wan Mohamud, Wan Nazaimoon; Östenson, Claes-Göran; Brismar, Kerstin; Gu, Harvest F

    2015-01-01

    Recent research has implicated that the inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation. In the present study, we carried out genetic, epigenetic and protein analyses of ICAM-1 in a Malaysian population, including normal glucose tolerance (NGT) subjects and type 2 diabetes (T2D) patients with or without DN in order to evaluate its role in DN. Analyses of DNA polymorphism and methylation in the ICAM1 gene were performed with TaqMan allelic discrimination and pyrosequencing, respectively. Plasma ICAM-1 levels were determined using an enzyme-linked immune-sorbent assay kit. We found that the ICAM1 K469E(A/G) polymorphism (rs5498) was significantly associated with DN. Particularly, 86.1% of T2D patients with DN carried heterozygous genotype compared to the patients without DN (68.6%). Furthermore, plasma ICAM-1 levels were increased from NGT subjects to T2D patients without and with DN (P<0.001). The NGT subjects carrying heterozygous genotype had significantly lower plasma ICAM-1 levels compared to the K469(A/A) genotype carriers (P=0.009). In the ICAM1 gene promoter, DNA methylation levels of CpG sites were low, and no association of the ICAM1 DNA methylation alteration with DN was detected. The present study provided evidence that the ICAM1 K469E(A/G) polymorphism with high heterozygous index and elevation of plasma ICAM-1 levels were associated with DN in a Malaysian population. Further prospective study of ICAM-1 protein according to the ICAM1 K469E(A/G) genotypes is necessary for predicting the susceptibility to T2D and DN. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Anode composite for molten carbonate fuel cell

    DOEpatents

    Iacovangelo, Charles D.; Zarnoch, Kenneth P.

    1983-01-01

    An anode composite useful for a molten carbonate fuel cell comprised of a porous sintered metallic anode component having a porous bubble pressure barrier integrally sintered to one face thereof, said barrier being comprised of metal coated ceramic particles sintered together and to said anode by means of said metal coating, said metal coating enveloping said ceramic particle and being selected from the group consisting of nickel, copper and alloys thereof, the median pore size of the barrier being significantly smaller than that of the anode.

  4. Diamond Nanoparticles Modify Curcumin Activity: In Vitro Studies on Cancer and Normal Cells and In Ovo Studies on Chicken Embryo Model

    PubMed Central

    Strojny, Barbara; Grodzik, Marta; Sawosz, Ewa; Winnicka, Anna; Kurantowicz, Natalia; Jaworski, Sławomir; Kutwin, Marta; Urbańska, Kaja; Hotowy, Anna; Wierzbicki, Mateusz; Chwalibog, André

    2016-01-01

    Curcumin has been studied broadly for its wide range of biological activities, including anticancer properties. The major problem with curcumin is its poor bioavailability, which can be improved by the addition of carriers, such as diamond nanoparticles (DN). They are carbon allotropes, and are therefore biocompatible and easily taken up by cells. DN are non-toxic and have antiangiogenic properties with potential applications in cancer therapy. Their large surface makes them promising compounds in a drug delivery system for bioactive agents, as DN create bio-complexes in a fast and simple process of self-organisation. We investigated the cytotoxicity of such bio-complexes against liver cancer cells and normal fibroblasts, revealing that conjugation of curcumin with DN significantly improves its activity. The experiment performed in a chicken embryo model demonstrated that neither curcumin nor DN nor bio-complexes affect embryo development, even though DN can form deposits in tissues. Preliminary results confirmed the applicability of DN as an efficient carrier of curcumin, which improves its performance against cancer cells in vitro, yet is not toxic to an organism, which makes the bio-complex a promising anticancer agent. PMID:27736939

  5. Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model.

    PubMed

    Stringer, Megan; Abeysekera, Irushi; Dria, Karl J; Roper, Randall J; Goodlett, Charles R

    2015-11-01

    Down syndrome (DS) or Trisomy 21 causes intellectual disabilities in humans and the Ts65Dn DS mouse model is deficient in learning and memory tasks. DYRK1A is triplicated in DS and Ts65Dn mice. Ts65Dn mice were given up to ~20mg/kg/day epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, or water beginning on postnatal day 24 and continuing for three or seven weeks, and were tested on a series of behavioral and learning tasks, including a novel balance beam test. Ts65Dn as compared to control mice exhibited higher locomotor activity, impaired novel object recognition, impaired balance beam and decreased spatial learning and memory. Neither EGCG treatment improved performance of the Ts65Dn mice on these tasks. Ts65Dn mice had a non-significant increase in Dyrk1a activity in the hippocampus and cerebellum. Given the translational value of the Ts65Dn mouse model, further studies will be needed to identify the EGCG doses (and mechanisms) that may improve cognitive function. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Diamond Nanoparticles Modify Curcumin Activity: In Vitro Studies on Cancer and Normal Cells and In Ovo Studies on Chicken Embryo Model.

    PubMed

    Strojny, Barbara; Grodzik, Marta; Sawosz, Ewa; Winnicka, Anna; Kurantowicz, Natalia; Jaworski, Sławomir; Kutwin, Marta; Urbańska, Kaja; Hotowy, Anna; Wierzbicki, Mateusz; Chwalibog, André

    2016-01-01

    Curcumin has been studied broadly for its wide range of biological activities, including anticancer properties. The major problem with curcumin is its poor bioavailability, which can be improved by the addition of carriers, such as diamond nanoparticles (DN). They are carbon allotropes, and are therefore biocompatible and easily taken up by cells. DN are non-toxic and have antiangiogenic properties with potential applications in cancer therapy. Their large surface makes them promising compounds in a drug delivery system for bioactive agents, as DN create bio-complexes in a fast and simple process of self-organisation. We investigated the cytotoxicity of such bio-complexes against liver cancer cells and normal fibroblasts, revealing that conjugation of curcumin with DN significantly improves its activity. The experiment performed in a chicken embryo model demonstrated that neither curcumin nor DN nor bio-complexes affect embryo development, even though DN can form deposits in tissues. Preliminary results confirmed the applicability of DN as an efficient carrier of curcumin, which improves its performance against cancer cells in vitro, yet is not toxic to an organism, which makes the bio-complex a promising anticancer agent.

  7. Improving Protein Fold Recognition by Deep Learning Networks.

    PubMed

    Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

    2015-12-04

    For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl's benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

  8. Effect of Tongxinluo on Podocyte Apoptosis via Inhibition of Oxidative Stress and P38 Pathway in Diabetic Rats

    PubMed Central

    Cui, Fangqiang; Zhao, Wenjing; Zou, Dawei; Wu, Xiaoming; Tian, Nianxiu; Wang, Xiaolei; Liu, Jing; Tong, Yu

    2016-01-01

    Diabetic nephropathy (DN) has been the leading cause of end-stage renal disease (ESRD). Podocyte apoptosis is a main mechanism of progression of DN. It has been demonstrated that activated P38 and caspase-3 induced by oxidative stress mainly account for increased podocyte apoptosis and proteinuria in DN. Meanwhile, Tongxinluo (TXL) can ameliorate renal structure disruption and dysfunction in DN patients in our clinical practice. However, the effect of TXL on podocyte apoptosis and P38 pathway remains unclear. To explore the effect of TXL on podocyte apoptosis and its molecular mechanism in DN, our in vivo and in vitro studies were performed. TXL attenuated oxidative stress in podocyte in DN in our in vivo and in vitro studies. Moreover, TXL inhibited the activation of P38 and caspase-3. Bcl-2 and Bax expression was partially restored by TXL treatment in our in vivo and in vitro studies. More importantly, TXL decreased podocyte apoptosis in diabetic rats and high glucose cultured podocyte. In conclusion, TXL protects podocyte from apoptosis in DN, partially through its antioxidant effect and inhibiting of the activation of P38 and caspase-3. PMID:27672400

  9. Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome

    PubMed Central

    Powers, Brian E.; Velazquez, Ramon; Kelley, Christy M.; Ash, Jessica A.; Strawderman, Myla S.; Alldred, Melissa J.; Ginsberg, Stephen D.; Mufson, Elliott J.

    2016-01-01

    Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs. PMID:26719290

  10. Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome.

    PubMed

    Powers, Brian E; Velazquez, Ramon; Kelley, Christy M; Ash, Jessica A; Strawderman, Myla S; Alldred, Melissa J; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

    2016-12-01

    Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs.

  11. 22 CFR 121.1 - General. The United States Munitions List.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... specifically designed or modified for the articles in this category: * (1) Guidance and control components for... controls of the ITAR. (f) Developmental aircraft, engines, and components thereof specifically designed... (including propellers) designed exclusively for civil, non-military aircraft (see § 121.3 of this subchapter...

  12. 22 CFR 121.1 - General. The United States Munitions List.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... specifically designed or modified for the articles in this category: * (1) Guidance and control components for... controls of the ITAR. (f) Developmental aircraft, engines, and components thereof specifically designed... (including propellers) designed exclusively for civil, non-military aircraft (see § 121.3 of this subchapter...

  13. 78 FR 20137 - Certain Sleep-Disordered Breathing Treatment Systems and Components Thereof; Notice of Receipt of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... INTERNATIONAL TRADE COMMISSION [Docket No. 2948] Certain Sleep-Disordered Breathing Treatment... given that the U.S. International Trade Commission has received a complaint entitled Certain Sleep... United States after importation of certain sleep- disordered breathing treatment systems and components...

  14. Clinicopathological characteristics of non-diabetic renal disease in patients with type 2 diabetes mellitus in a northeastern Chinese medical center: a retrospective analysis of 273 cases.

    PubMed

    Liu, Shujun; Guo, Qiaoyan; Han, Hongbo; Cui, Peihe; Liu, Xiao; Miao, Lining; Zou, Hongbin; Sun, Guangdong

    2016-10-01

    To investigate the clinical and histopathological features of non-diabetic renal disease (NDRD) superimposed on diabetic nephropathy (DN) in northeastern Chinese patients with type 2 diabetes mellitus (T2D), and compare the changes with those of pure DN and isolated NDRD. Single-center retrospective analysis based on medical records of 273 patients (172 men, mean age: 51.1 ± 12.4 years) with T2D who underwent renal biopsy between February 2000 and October 2015. All patients were diagnosed as cases of pure DN, isolated NDRD or NDRD superimposed on DN. Out of the 273 T2D patients, 68 (24.9 %) had DN, 175 (64.1 %) had NDRD, and 30 (11.0 %) had NDRD superimposed on DN. Idiopathic membranous nephropathy (IMN, 29.7 %) was the most common NDRD followed by IgA nephropathy (IgAN, 22.9 %), and hypertensive renal arteriolar sclerosis was the most common lesion in patients diagnosed as NDRD superimposed on DN. Patients with NDRD had a shorter duration of diabetes and lower frequencies of diabetic retinopathy (DR, 6.9 %) and renal failure (28.0 %), which is consistent with higher estimated glomerular filtration rates (eGFR) and lower systolic blood pressure (SBP). No significant between-group differences were observed with respect to proteinuria and hematuria. Renal biopsy is strongly recommended for T2D patients to distinguish DN, NDRD and NDRD superimposed on DN, especially in patients with no signs of DR. This approach may help in early diagnosis and treatment of NDRD and improve renal outcomes in northeastern Chinese T2D patients.

  15. SOCS2 overexpression alleviates diabetic nephropathy in rats by inhibiting the TLR4/NF-κB pathway

    PubMed Central

    Yang, Suxia; Zhang, Junwei; Wang, Shiying; Zhao, Xinxin; Shi, Jun

    2017-01-01

    Suppressor of cytokine signaling 2 (SOCS2) was reported to be involved in the development of Diabetic Nephropathy (DN). However, its underlying mechanism remains undefined. Western blot was carried out to determine the expressions of SOCS2, Toll-like receptors 4 (TLR4) and nuclear factor kappa B (NF-κB) pathway-related proteins in DN patients, streptozotocin (STZ)-induced DN rats and high glucose (HG)-stimulated podocytes. The effects of SOCS2 overexpression on renal injury, the inflammatory cytokines production, renal pathological changes, apoptosis and the TLR4/NF-κB pathway in DN rats or HG-stimulated podocytes were investigated. TLR4 antagonist TAK-242 and NF-κB inhibitor PDTC were used to confirm the functional mechanism of SOCS2 overexpression in HG-stimulated podocytes. SOCS2 was down-regulated, while TLR4 and NF-κB were up-regulated in renal tissues of DN patients and DN rats. Ad-SOCS2 infection alleviated STZ-induced renal injury and pathological changes and inhibited STZ-induced IL-6, IL-1β and MCP-1 generation and activation of the TLR4/NF-κB pathway in DN rats. SOCS2 overexpression attenuated apoptosis, suppressed the inflammatory cytokines expression, and inactivated the TLR4/NF-κB pathway in HG-stimulated podocytes. Suppression of the TLR4/NF-κB pathway enhanced the inhibitory effect of SOCS2 overexpression on apoptosis and inflammatory cytokines expressions in HG-stimulated podocytes. SOCS2 overexpression alleviated the development of DN by inhibiting the TLR4/NF-κB pathway, contributing to developing new therapeutic strategies against DN. PMID:29207635

  16. Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome.

    PubMed

    Kelley, Christy M; Ash, Jessica A; Powers, Brian E; Velazquez, Ramon; Alldred, Melissa J; Ikonomovic, Milos D; Ginsberg, Stephen D; Strupp, Barbara J; Mufson, Elliott J

    2016-01-01

    Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer's disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice compared to 2N mice sacrificed at 6-8 and 14-18 months of age. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6-8 and 14-18 mos were used for an aging study and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14-18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in Ts65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS.

  17. Therapeutic effects of dry needling in patients with upper trapezius myofascial trigger points

    PubMed Central

    Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

    2017-01-01

    Background Active myofascial trigger points (MTrPs) are major pain generators in myofascial pain syndrome. Dry needling (DN) is an effective method for the treatment of MTrPs. Objective To assess the immediate neurophysiological and clinical effects of DN in patients with upper trapezius MTrPs. Methods This was a prospective, clinical trial study of 20 patients with upper trapezius MTrPs and 20 healthy volunteers (matched for height, weight, body mass index and age), all of whom received one session of DN. Primary outcome measures were neuromuscular junction response (NMJR) and sympathetic skin response (SSR). Secondary outcomes were pain intensity (PI) and pressure pain threshold (PPT). Data were collected at baseline and immediately post-intervention. Results At baseline, SSR amplitude was higher in patients versus healthy volunteers (p<0.003). With respect to NMJR, a clinically abnormal increment and normal reduction was observed in patients and healthy volunteers, respectively. Moreover, PPT of patients was less than healthy volunteers (p<0.0001). After DN, SSR amplitude decreased significantly in patients (p<0.01), but did not change in healthy volunteers. A clinically important reduction in the NMJR of patients and increment in healthy volunteers was demonstrated after DN. PPT increased after DN in patients, but decreased in healthy volunteers (p<0.0001). PI improved after DN in patients (p<0.001). Conclusions The results of this study showed that one session of DN targeting active MTrPs appears to reduce hyperactivity of the sympathetic nervous system and irritability of the motor endplate. DN seems effective at improving symptoms and deactivating active MTrPs, although further research is needed. Trial registration number IRCT20130316128. PMID:27697768

  18. Therapeutic effects of dry needling in patients with upper trapezius myofascial trigger points.

    PubMed

    Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

    2017-04-01

    Active myofascial trigger points (MTrPs) are major pain generators in myofascial pain syndrome. Dry needling (DN) is an effective method for the treatment of MTrPs. To assess the immediate neurophysiological and clinical effects of DN in patients with upper trapezius MTrPs. This was a prospective, clinical trial study of 20 patients with upper trapezius MTrPs and 20 healthy volunteers (matched for height, weight, body mass index and age), all of whom received one session of DN. Primary outcome measures were neuromuscular junction response (NMJR) and sympathetic skin response (SSR). Secondary outcomes were pain intensity (PI) and pressure pain threshold (PPT). Data were collected at baseline and immediately post-intervention. At baseline, SSR amplitude was higher in patients versus healthy volunteers (p<0.003). With respect to NMJR, a clinically abnormal increment and normal reduction was observed in patients and healthy volunteers, respectively. Moreover, PPT of patients was less than healthy volunteers (p<0.0001). After DN, SSR amplitude decreased significantly in patients (p<0.01), but did not change in healthy volunteers. A clinically important reduction in the NMJR of patients and increment in healthy volunteers was demonstrated after DN. PPT increased after DN in patients, but decreased in healthy volunteers (p<0.0001). PI improved after DN in patients (p<0.001). The results of this study showed that one session of DN targeting active MTrPs appears to reduce hyperactivity of the sympathetic nervous system and irritability of the motor endplate. DN seems effective at improving symptoms and deactivating active MTrPs, although further research is needed. IRCT20130316128. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome

    PubMed Central

    Kelley, Christy M.; Ash, Jessica A.; Powers, Brian E.; Velazquez, Ramon; Alldred, Melissa J.; Ikonomovic, Milos D.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

    2016-01-01

    Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer’s disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6–8 and 14–18 mos were used for an aging study, and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14–18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in TS65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS. PMID:26391045

  20. Genetic interaction between two insulin-dependent diabetes susceptibility loci, Idd2 and Idd13, in determining immunoregulatory DN T cell proportion.

    PubMed

    Collin, Roxanne; Doyon, Kathy; Mullins-Dansereau, Victor; Karam, Martin; Chabot-Roy, Geneviève; Hillhouse, Erin E; Orthwein, Alexandre; Lesage, Sylvie

    2018-04-25

    Several immune regulatory cell types participate in the protection against autoimmune diseases such as autoimmune diabetes. Of these immunoregulatory cells, we and others have shown that peripheral CD4 - CD8 - double negative (DN) T cells can induce antigen-specific immune tolerance. Particularly, we have described that diabetes-prone mice exhibit a lower number of peripheral DN T cells compared to diabetes-resistant mice. Identifying the molecular pathways that influence the size of the DN T cell pool in peripheral lymphoid organs may thus be of interest for maintaining antigen-specific immune tolerance. Hence, through immunogenetic approaches, we found that two genetic loci linked to autoimmune diabetes susceptibility, namely Idd2 and Idd13, independently contribute to the partial restoration of DN T cell proportion in secondary lymphoid organs. We now extend these findings to show an interaction between the Idd2 and Idd13 loci in determining the number of DN T cells in secondary lymphoid organs. Using bioinformatics tools, we link potential biological pathways arising from interactions of genes encoded within the two loci. By focusing on cell cycle, we validate that both the Idd2 and Idd13 loci influence RAD51 expression as well as DN T cell progression through the cell cycle. Altogether, we find that genetic interactions between Idd2 and Idd13 loci modulate cell cycle progression, which contributes, at least in part, to defining the proportion of DN T cells in secondary lymphoid organs.

  1. 46 CFR 58.30-35 - Testing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... components thereof shall be tested as required by this section. (b) Accumulators constructed as pressure... associated equipment components, including hydraulic steering gear, in lieu of being tested at the time of installation, may be shop tested by the manufacturer to 11/2 times the maximum allowable pressure of the system...

  2. 46 CFR 58.30-35 - Testing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... components thereof shall be tested as required by this section. (b) Accumulators constructed as pressure... associated equipment components, including hydraulic steering gear, in lieu of being tested at the time of installation, may be shop tested by the manufacturer to 11/2 times the maximum allowable pressure of the system...

  3. 46 CFR 58.30-35 - Testing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... components thereof shall be tested as required by this section. (b) Accumulators constructed as pressure... associated equipment components, including hydraulic steering gear, in lieu of being tested at the time of installation, may be shop tested by the manufacturer to 11/2 times the maximum allowable pressure of the system...

  4. 46 CFR 58.30-35 - Testing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... components thereof shall be tested as required by this section. (b) Accumulators constructed as pressure... associated equipment components, including hydraulic steering gear, in lieu of being tested at the time of installation, may be shop tested by the manufacturer to 11/2 times the maximum allowable pressure of the system...

  5. 46 CFR 58.30-35 - Testing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... components thereof shall be tested as required by this section. (b) Accumulators constructed as pressure... associated equipment components, including hydraulic steering gear, in lieu of being tested at the time of installation, may be shop tested by the manufacturer to 11/2 times the maximum allowable pressure of the system...

  6. 30 CFR 27.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PRODUCTS METHANE-MONITORING SYSTEMS General Provisions § 27.1 Purpose. The regulations in this part set forth the requirements for methane-monitoring systems or components thereof to procure certification for...

  7. 30 CFR 27.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PRODUCTS METHANE-MONITORING SYSTEMS General Provisions § 27.1 Purpose. The regulations in this part set forth the requirements for methane-monitoring systems or components thereof to procure certification for...

  8. Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

    PubMed Central

    Min, Xu; Xu, Xiaohong

    2017-01-01

    Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies. PMID:28512642

  9. Personality and complex brain networks: The role of openness to experience in default network efficiency

    PubMed Central

    Kaufman, Scott Barry; Benedek, Mathias; Jung, Rex E.; Kenett, Yoed N.; Jauk, Emanuel; Neubauer, Aljoscha C.; Silvia, Paul J.

    2015-01-01

    Abstract The brain's default network (DN) has been a topic of considerable empirical interest. In fMRI research, DN activity is associated with spontaneous and self‐generated cognition, such as mind‐wandering, episodic memory retrieval, future thinking, mental simulation, theory of mind reasoning, and creative cognition. Despite large literatures on developmental and disease‐related influences on the DN, surprisingly little is known about the factors that impact normal variation in DN functioning. Using structural equation modeling and graph theoretical analysis of resting‐state fMRI data, we provide evidence that Openness to Experience—a normally distributed personality trait reflecting a tendency to engage in imaginative, creative, and abstract cognitive processes—underlies efficiency of information processing within the DN. Across two studies, Openness predicted the global efficiency of a functional network comprised of DN nodes and corresponding edges. In Study 2, Openness remained a robust predictor—even after controlling for intelligence, age, gender, and other personality variables—explaining 18% of the variance in DN functioning. These findings point to a biological basis of Openness to Experience, and suggest that normally distributed personality traits affect the intrinsic architecture of large‐scale brain systems. Hum Brain Mapp 37:773–779, 2016. © 2015 Wiley Periodicals, Inc. PMID:26610181

  10. Surface Electromyographic Activity of the Upper Trapezius Before and After a Single Dry Needling Session in Female Office Workers With Trapezius Myalgia.

    PubMed

    De Meulemeester, Kayleigh; Calders, Patrick; Dewitte, Vincent; Barbe, Tom; Danneels, Lieven; Cagnie, Barbara

    2017-12-01

    Myofascial pain can be accompanied by a disturbed surface electromyographic (sEMG) activity. Nevertheless, the effect of myofascial treatment techniques, such as dry needling (DN), on the sEMG activity is poorly investigated. Several DN studies also emphasize the importance of eliciting local twitch responses (LTRs) during treatment. However, studies investigating the added value of LTRs are scarce. Therefore, the aims of this study were first to evaluate the effect of DN on the sEMG activity of myalgic muscle tissue, compared with no intervention (rest), and secondly to identify whether this effect is dependent of eliciting LTRs during DN. Twenty-four female office workers with work-related trapezius myalgia were included. After completion of a typing task, changes in sEMG activity were evaluated after a DN treatment of the upper trapezius, compared with rest. The sEMG activity increased after rest and after DN, but this increase was significantly smaller 10 minutes after DN, compared with rest. These differences were independent whether LTRs were elicited or not. Dry needling leads to a significantly lower increase in sEMG activity of the upper trapezius, compared with no intervention, after a typing task. This difference was independent of eliciting LTRs.

  11. [Research on land use structure optimization based on nonpoint source dissolved nitrogen load estimation in Shuaishui watershed].

    PubMed

    Lu, Yu-Chao; Bi, Meng-Fei; Li, Ze-Li; Sha, Jian; Wang, Yu-Qiu; Qian, Li-Ping

    2014-06-01

    Regional Nutrient Management (ReNuMa) was applied to estimate dissolved nitrogen (DN) load and perform source apportionment in Shuaishui watershed during 2000-2010. Satisfactory performance of ReNuMa was revealed by the E(ns) and R2 of greater than 0.9 in calibrating and validating streamflow and DN. The average nonpoint DN load in this watershed was 1.11 x 10(3) t x a(-1), with the load intensity of (0.75 +/- 0.22) t x km(-2). Among all the land uses, paddy field had the largest DN load intensity [28.60 kg x (hm2 x a)(-1)], while forest had the least [2.71 kg x (hm2 x a)(-1)]. Agricultural land (including paddy, grain, cash crop, tea plant and orchard) contributed most to DN load in Shuaishui watershed, indicating that the human dominated agricultural activities was the major contributor of nonpoint source pollution. Land use structure optimization for Shuaishui watershed in 2015 was conducted under the rule of reducing pollutants loads and maximizing the agricultural output value. The results demonstrated that agricultural monetary growth was accompanied with the increasing DN load at the optimal level, although output increment was higher than that of DN load.

  12. Improving Protein Fold Recognition by Deep Learning Networks

    NASA Astrophysics Data System (ADS)

    Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

    2015-12-01

    For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl’s benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

  13. Enhanced catalyst for converting synthesis gas to liquid motor fuels

    DOEpatents

    Coughlin, Peter K.

    1986-01-01

    The conversion of synthesis gas to liquid molar fuels by means of a cobalt Fischer-Tropsch catalyst composition is enhanced by the addition of molybdenum, tungsten or a combination thereof as an additional component of said composition. The presence of the additive component increases the olefinic content of the hydrocarbon products produced. The catalyst composition can advantageously include a support component, such as a molecular sieve, co-catalyst/support component or a combination of such support components.

  14. 32 CFR 310.51 - General.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... agency, or a component thereof, whose principal function is the enforcement of criminal laws, subsequent to the initiation of a specific criminal or civil law enforcement investigation of a named individual...

  15. 32 CFR 310.51 - General.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... agency, or a component thereof, whose principal function is the enforcement of criminal laws, subsequent to the initiation of a specific criminal or civil law enforcement investigation of a named individual...

  16. 32 CFR 310.51 - General.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... agency, or a component thereof, whose principal function is the enforcement of criminal laws, subsequent to the initiation of a specific criminal or civil law enforcement investigation of a named individual...

  17. 32 CFR 310.51 - General.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... agency, or a component thereof, whose principal function is the enforcement of criminal laws, subsequent to the initiation of a specific criminal or civil law enforcement investigation of a named individual...

  18. 32 CFR 310.51 - General.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... agency, or a component thereof, whose principal function is the enforcement of criminal laws, subsequent to the initiation of a specific criminal or civil law enforcement investigation of a named individual...

  19. The App-Runx1 Region Is Critical for Birth Defects and Electrocardiographic Dysfunctions Observed in a Down Syndrome Mouse Model

    PubMed Central

    Raveau, Matthieu; Lignon, Jacques M.; Nalesso, Valérie; Duchon, Arnaud; Groner, Yoram; Sharp, Andrew J.; Dembele, Doulaye; Brault, Véronique; Hérault, Yann

    2012-01-01

    Down syndrome (DS) leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG) with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf) and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1). In addition cardiac connexins (Cx40, Cx43) and sodium channel sub-units (Scn5a, Scn1b, Scn10a) were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people. PMID:22693452

  20. Niabella hibiscisoli sp. nov., isolated from soil of a Rose of Sharon garden.

    PubMed

    Ngo, Hien T T; Trinh, Huan; Yan, Zheng-Fei; Moya, Gabriela; Kook, MooChang; Yi, Tae-Hoo

    2017-04-01

    A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped and yellow-pigmented bacterium, designated strain THG-DN5.5T, was isolated from soil of a Rose of Sharon garden in Daejeon, South Korea. According to 16S rRNA gene sequence comparisons, strain THG-DN5.5T was found to be most closely related to Niabella yanshanensis CCBAU 05354T (97.7 % sequence similarity), Niabella ginsengisoli GR10-1T (97.0 %), 'Niabella terrae' ICM 1-15 (96.0 %), Niabella soli DSM 19437T (95.7 %) and Niabella aquatica RP-2T (95.6 %). The DNA-DNA relatedness between strain THG-DN5.5T and its phylogenetically closest neighbours was below 50.0 %. The DNA G+C content was 43.1 mol%. The major polar lipid of strain THG-DN5.5T was found to be phosphatidylethanolamine. The major fatty acids were identified as C16 : 0, iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. MK-7 was the only menaquinone present. These data supported the affiliation of strain THG-DN5.5T to the genus Niabella. Strain THG-DN5.5T was distinguished from related species of the genus Niabellaby physiological and biochemical tests. In conclusion, strain THG-DN5.5T represents a novel species of the genus Niabella, for which the name Niabella hibiscisolisp. nov. is proposed. The type strain is THG-DN5.5T (=KACC 18857T=CCTCC AB 2016086T).

  1. LSI Applications.

    DTIC Science & Technology

    1982-07-01

    of emula- tion in more detail. System components such as memories and I/O interfaces are also represen- ted in the emulation so that the complete...engineeAing Aupp4t wUn a..u oi teeicA. Cmpete ia lp’ovUed to ESP Pu a f 1c ( POe1 mid otbtA ESP eteMeftb. The Pt.Lnept tesf&A Uif dn 0 M e 4c.Ou~w~C. 04

  2. Raman biophysical markers in skin cancer diagnosis.

    PubMed

    Feng, Xu; Moy, Austin J; Nguyen, Hieu T M; Zhang, Yao; Zhang, Jason; Fox, Matthew C; Sebastian, Katherine R; Reichenberg, Jason S; Markey, Mia K; Tunnell, James W

    2018-05-01

    Raman spectroscopy (RS) has demonstrated great potential for in vivo cancer screening; however, the biophysical changes that occur for specific diagnoses remain unclear. We recently developed an inverse biophysical skin cancer model to address this issue. Here, we presented the first demonstration of in vivo melanoma and nonmelanoma skin cancer (NMSC) detection based on this model. We fit the model to our previous clinical dataset and extracted the concentration of eight Raman active components in 100 lesions in 65 patients diagnosed with malignant melanoma (MM), dysplastic nevi (DN), basal cell carcinoma, squamous cell carcinoma, and actinic keratosis. We then used logistic regression and leave-one-lesion-out cross validation to determine the diagnostically relevant model components. Our results showed that the biophysical model captures the diagnostic power of the previously used statistical classification model while also providing the skin's biophysical composition. In addition, collagen and triolein were the most relevant biomarkers to represent the spectral variances between MM and DN, and between NMSC and normal tissue. Our work demonstrates the ability of RS to reveal the biophysical basis for accurate diagnosis of different skin cancers, which may eventually lead to a reduction in the number of unnecessary excisional skin biopsies performed. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  3. OCTANOL/WATER PARTITION COEFFICIENTS AND WATER SOLUBILITIES OF PHTHALATE ESTERS

    EPA Science Inventory

    Measurements of the octanol/water partition coefficients (K-ow) and water solubilities of di-n-octyl phthalate (DnOP) and di-n-decyl phthalate (DnDP) by the slow-stirring method are reported. The water solubility was also measured for di-n-hexyl phthalate (DnHP). The log K-ow val...

  4. Peripheral neuropathy in children with type 1 diabetes.

    PubMed

    Louraki, M; Karayianni, C; Kanaka-Gantenbein, C; Katsalouli, M; Karavanaki, K

    2012-10-01

    Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. Naringin ameliorates diabetic nephropathy by inhibiting NADPH oxidase 4.

    PubMed

    Zhang, Junwei; Yang, Suxia; Li, Huicong; Chen, Fang; Shi, Jun

    2017-06-05

    Naringin, a naturally flavanone glycoside, has been previously demonstrated to alleviate diabetic kidney disease by inhibiting oxidative stress and inflammatory reaction. However, the underlying mechanism of naringin in diabetic nephropathy (DN) has not been fully elucidated. Here, the beneficial effect of naringin on DN in streptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes and its underlying mechanism were elaborated. The result revealed that naringin alleviated STZ-induced renal dysfunction and injury in DN rats, relieved STZ-induced oxidative stress in vivo and inhibited HG-induced apoptosis and reactive oxygen species level i20n vitro. More importantly, naringin inhibited NOX4 expression at mRNA and protein levels in STZ-induced DN rats and HG-induced podocytes. Loss of function indicated that NADPH oxidases 4 (NOX4) down-regulation suppressed apoptosis and reactive oxygen species level in HG-treated podocytes. Take together, this study demonstrated that naringin ameliorates diabetic nephropathy by inhibiting NOX4, contributing to a better understanding of the progression of DN. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 30 CFR 27.7 - Certification plate or label.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS METHANE-MONITORING SYSTEMS General Provisions § 27.7 Certification plate or label. A certified methane-monitoring system or component thereof shall be identified with a...

  7. 30 CFR 27.7 - Certification plate or label.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... APPROVAL OF MINING PRODUCTS METHANE-MONITORING SYSTEMS General Provisions § 27.7 Certification plate or label. A certified methane-monitoring system or component thereof shall be identified with a...

  8. The Prevalence and Management of Diabetic Nephropathy in Asia

    PubMed Central

    Tomino, Yasuhiko; Gohda, Tomohito

    2015-01-01

    Background Diabetic nephropathy (DN), especially type 2 diabetes, is now increasing rapidly worldwide, also in Asian countries, and is one of the major long-term vascular complications. The pathogenesis of DN involves both genetic and environmental factors. Around 30-40% of type 2 diabetic patients develop DN despite strict blood glucose and/or blood pressure control. Although it is considered that the genetic background may influence the initiation and progression of DN, the candidate genes are still obscure. Summary To search for genes that are involved in the susceptibility of DN, a candidate gene approach was taken in the beginning before the development of genome-wide association studies. Although a candidate gene approach can detect rare genetic variants, in advance we need known or presumed pathophysiological knowledge of the specific gene. Investigations using spontaneous animal models are important to determine the pathogenesis and treatment of DN patients. There are many spontaneous animal models, such as the NOD and Akita mice for type 1 diabetes and the Ob/Ob, db/db, Tsumura Suzuki Obese Diabetics, and KK-Ay mice for type 2 diabetes. Furthermore, the toxicity of persistent hyperglycemia, the activation of reactive oxygen species, systemic and/or glomerular hypertension, microinflammation, dyslipidemia, and other factors are considered to play important roles. Diabetic patients with normoalbuminuria and normal renal function showed typical histological patterns of DN. The discovery of a specific and reliable diagnostic and prognostic biomarker other than albuminuria is urgently needed and indispensable. Since large clinical trials of oral hypoglycemic drugs in renal failure are lacking, these recommendations will need to be regularly updated after results of larger randomized trials with longer follow-up durations are available. Key Message It is necessary to summarize the basic and clinical features of DN patients in Asia and to use these for the treatment of such patients. Facts from East and West The prevalence of DN is increasing in Asia and Western countries alike. The deletion (D) allele of the angiotensin-converting enzyme gene is associated with progression to end-stage renal disease in Asian patients with DN, but this association is uncertain in Europeans. An association between DN and polymorphism of the gene coding for acetyl coenzyme A carboxylase β has been reported in Asian and Western populations. Both in Japan and the US, criteria for diagnosis are a 5-year history of diabetes and persistent albuminuria. Renal biopsy should be done in patients with severe hematuria, cellular casts and - in the US - hepatitis and HIV to rule out other pathologies. Diabetic retinopathy is considered a key criterion in Japan, but the absence of it does not rule out DN in the US. Enlargement of the kidney is observed as a diagnostic criterion in Japan. The differential use of renal biopsy as diagnostic tool might account for a different prevalence between Asian countries. Some Japanese diabetic patients showed typical histological alterations for DN with a normal ACR and GFR. The clinical classification is similar between Japan and the US including five stages based on ACR and GFR. The Japanese guidelines do not include blood pressure values for the classification of DN. Guidelines for DN treatment are evolving quickly both in Asia and Western countries based on the numerous clinical trials performed worldwide. Targeting the angiotensin system for its hemodynamic and nonhemodynamic effects is a common approach. DPP-4 inhibitors are widely used in Japan and might have a higher glucose-lowering effect in Asian patients due to their specific diet. A randomized, double-blind placebo-controlled study has been launched to assess the efficacy of the Chinese herbal tea extract Shenyan Kangfu in DN. PMID:27536665

  9. Switchable solvents and methods of use thereof

    DOEpatents

    Jessop, Philip G.; Eckert, Charles A.; Liotta, Charles L.; Heldebrant, David J.

    2013-08-20

    A solvent that reversibly converts from a nonionic liquid mixture to an ionic liquid upon contact with a selected trigger, e.g., contact with CO.sub.2, is described. In preferred embodiments, the ionic solvent is readily converted back to the nonionic liquid mixture. The nonionic liquid mixture includes an amidine or guanidine or both, and water, alcohol, or a combination thereof. Single component amine solvents that reversibly convert between ionic and non-ionic states are also described. Some embodiments require increased pressure to convert; others convert at 1 atmosphere.

  10. Switchable solvents and methods of use thereof

    DOEpatents

    Jessop, Philip G [Kingston, CA; Eckert, Charles A [Atlanta, GA; Liotta, Charles L [Atlanta, GA; Heldebrant, David J [Richland, WA

    2011-07-19

    A solvent that reversibly converts from a nonionic liquid mixture to an ionic liquid upon contact with a selected trigger, e.g., contact with CO.sub.2, is described. In preferred embodiments, the ionic solvent is readily converted back to the nonionic liquid mixture. The nonionic liquid mixture includes an amidine or guanidine or both, and water, alcohol, or a combination thereof. Single component amine solvents that reversibly convert between ionic and non-ionic states are also described. Some embodiments require increased pressure to convert; others convert at 1 atmosphere.

  11. Switchable solvents and methods of use thereof

    DOEpatents

    Jessop, Philip G; Eckert, Charles A; Liotta, Charles L; Heldebrant, David J

    2014-04-29

    A solvent that reversibly converts from a nonionic liquid mixture to an ionic liquid upon contact with a selected trigger, e.g., contact with CO.sub.2, is described. In preferred embodiments, the ionic solvent is readily converted back to the nonionic liquid mixture. The nonionic liquid mixture includes an amidine or guanidine or both, and water, alcohol, or a combination thereof. Single component amine solvents that reversibly convert between ionic and non-ionic states are also described. Some embodiments require increased pressure to convert; others convert at 1 atmosphere.

  12. Landsat-7 ETM+ on-orbit reflective-band radiometric characterization

    USGS Publications Warehouse

    Scaramuzza, P.L.; Markham, B.L.; Barsi, J.A.; Kaita, E.

    2004-01-01

    The Landsat-7 Enhanced Thematic Mapper Plus (ETM+) has been and continues to be radiometrically characterized using the Image Assessment System (IAS), a component of the Landsat-7 Ground System. Key radiometric properties analyzed include: overall, coherent, and impulse noise; bias stability; relative gain stability; and other artifacts. The overall instrument noise is characterized across the dynamic range of the instrument during solar diffuser deployments. Less than 1% per year increases are observed in signal-independent (dark) noise levels, while signal-dependent noise is stable with time. Several coherent noise sources exist in ETM+ data with scene-averaged magnitudes of up to 0.4 DN, and a noise component at 20 kHz whose magnitude varies across the scan and peaks at the image edges. Bit-flip noise does not exist on the ETM+. However, impulse noise due to charged particle hits on the detector array has been discovered. The instrument bias is measured every scan line using a shutter. Most bands show less than 0.1 DN variations in bias across the instrument lifetime. The panchromatic band is the exception, where the variation approaches 2 DN and is related primarily to temperature. The relative gains of the detectors, i.e., each detector's gain relative to the band average gain, have been stable to /spl plusmn/0.1% over the mission life. Two exceptions to this stability include band 2 detector 2, which dropped about 1% in gain about 3.5 years after launch and stabilized, and band 7 detector 5, which has changed several tenths of a percent several times since launch. Memory effect and scan-correlated shift, a hysteresis and a random change in bias between multiple states, respectively, both of which have been observed in previous Thematic Mapper sensors, have not been convincingly found in ETM+ data. Two artifacts, detector ringing and "oversaturation", affect a small amount of ETM+ data.

  13. Cost-effectiveness Evaluation of the Inclusion of Dry Needling into an Exercise Program for Subacromial Pain Syndrome: Evidence from a Randomized Clinical Trial.

    PubMed

    Arias-Buría, José L; Martín-Saborido, Carlos; Cleland, Joshua; Koppenhaver, Shane L; Plaza-Manzano, Gustavo; Fernández-de-Las-Peñas, César

    2018-02-22

    To evaluate the cost-effectiveness of the inclusion of trigger point-dry needling (TrP-DN) into an exercise program for the management of subacromial pain syndrome. Fifty patients with unilateral subacromial pain syndrome were randomized with concealed allocation to exercise alone or exercise plus TrP-DN. Both groups were asked to perform an exercise program targeting the rotator cuff musculature twice daily for five weeks. Patients allocated to the exercise plus TrP-DN group also received dry needling during the second and fourth sessions. Societal costs and health-related quality of life (estimated by EuroQol-5D-5L) over a one-year follow-up were used to generate incremental cost per quality-adjusted life-year (QALY) ratios for each intervention.  Intention-to-treat analysis was possible for 48 (96%) of the participants. Those in the exercise group made more visits to medical doctors and received a greater number of other treatments (P < 0.001). The major contributor to societal costs (77%) was the absenteeism paid labor in favor of the exercise plus TrP-DN group (P = 0.03). The combination of exercise plus TrP-DN was less costly (mean difference cost/patient = €517.34, P = 0.003) than exercise alone. Incremental QALYs showed greater benefit for exercise plus TrP-DN (difference = 2.87, 95% confidence interval = 2.85-2.89). Therefore, the inclusion of TrP-DN into an exercise program was more likely to be cost-effective than an exercise program alone, with 99.5% of the iterations falling in the dominant area. The inclusion of TrP-DN into an exercise program was more cost-effective for individuals with subacromial pain syndrome than exercise alone. From a cost-benefit perspective, the inclusion of TrP-DN into multimodal management of patients with subacromial pain syndrome should be considered.

  14. Identification, prevalence, and treatment of painful diabetic neuropathy in patients from a rural area in South Carolina.

    PubMed

    Pruitt, Jimmy; Moracho-Vilrriales, Carolina; Threatt, Tiffaney; Wagner, Sarah; Wu, Jun; Romero-Sandoval, E Alfonso

    2017-01-01

    Diabetic peripheral neuropathy (DPN) represents significant burdens to many patients and the public health-care system. Patients with diabetes in rural areas have higher risk of developing complications and having less access to proper treatment. We studied a rural population of patients with diabetes who attended a pharmacist-led free clinic for a diabetic education program. Our objectives were to 1) determine the prevalence of DPN and painful diabetic neuropathy (p-DN) in patients with type 2 diabetes; 2) assess the proportion of patients with DPN and p-DN left undocumented upon physician referral to a pharmacist-led free clinic; and 3) determine the appropriateness of pain medication regimen. We performed a retrospective analysis of clinical records of patients from the Presbyterian College School of Pharmacy (PCSP) Wellness Center located in Clinton, SC. Diagnoses of DPN and/or p-DN were obtained from referral notes in the clinical records and compared with results from foot examinations performed in the free clinic and clinical features. Medication regimens were also obtained and compared using American Academy of Neurology (AAN) treatment guidelines. Within our study population (n=111), the prevalence of DPN was 62.2% (national average of 28%-45%) and that of p-DN was 23.4% (national average of 11%-24%). In p-DN patients (n=26), 53.8% (n=14) had a documented diagnosis of p-DN by the referring physician, and 46.2% (n=12) were identified by the pharmacists. A total of 95% (19 of 20) of the patients treated for p-DN received adequate pharmacological agents, though suboptimal as per clinical guidelines. More than 50% of the patients used subtherapeutic doses of their medications. Gabapentin was the most frequently used medication in our population (65.4%). Patients in rural South Carolina had a higher prevalence of DPN and p-DN with >60% undocumented cases of p-DN. More than 95% of treated patients did not receive optimum therapy according to AAN guidelines.

  15. Development and validation of Arabic version of the douleur neuropathique 4 questionnaire.

    PubMed

    Terkawi, Abdullah Sulieman; Abolkhair, Abdullah; Didier, Bouhassira; Alzhahrani, Tariq; Alsohaibani, Mazen; Terkawi, Yazzed Sulieman; Almoqbali, Yousuf; Tolba, Yasser Younis; Pangililan, Evelyn; Foula, Farida; Tsang, Siny

    2017-05-01

    The douleur neuropathique 4 (DN4) questionnaire is a widely used tool for diagnosis of neuropathic pain (NP). The aim was to translate, culturally adapt, and validate the DN4 questionnaire in Arabic. A systematic translation process was used to translate the original English DN4 into Arabic. After the pilot study, the Arabic version was validated among patients with chronic pain in two tertiary care centers. The reliability of the translated version was examined using internal consistency, test-retest reliability, and intraclass correlation coefficients. We examined the validity of the Arabic DN4 via construct validity, concurrent validity (associations with the numeric rating scale, brief pain inventory, and Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs [S-LANSS]), face validity, and diagnostic validity. To investigate the responsiveness, the translated DN4 was administered twice among the same group of patients. A total of 142 subjects (68 men, 74 women) were included in the study. Cronbach's α was 0.67 (95% confidence interval [CI]: 0.59-0.75), and interclass correlation coefficients was 0.81 (95% CI: 0.76-0.87). The DN4 was moderately associated with the S-LANSS questionnaire. Results showed our Arabic DN4 to have good diagnostic accuracy, with area under the curve of 0.88 (95% CI: 0.82-0.94). As with the original version, a score of ≥4 was found to be the best cut-off for the diagnosis of NP, with a sensitivity of 88.31%, specificity of 74.47%, a positive predictive value of 85%, and a negative predictive value of 80%. Most patients found the DN4 questionnaire to be clear and easy to understand, and thought the questionnaire items covered all their problem areas regarding their pain. Our Arabic version of the DN4 is a reliable and valid screening tool that can be easily administered among patients to differentiate between NP and non-NP.

  16. Potential Role of Serum and Urinary Biomarkers in Diagnosis and Prognosis of Diabetic Nephropathy.

    PubMed

    Campion, Carole G; Sanchez-Ferras, Oraly; Batchu, Sri N

    2017-01-01

    Diabetic nephropathy (DN) is a progressive kidney disease caused by alterations in kidney architecture and function, and constitutes one of the leading causes of end-stage renal disease (ESRD). The purpose of this review is to summarize the state of the art of the DN-biomarker field with a focus on the new strategies that enhance the sensitivity of biomarkers to predict patients who will develop DN or are at risk of progressing to ESRD. In this review, we provide a description of the pathophysiology of DN and propose a panel of novel putative biomarkers associated with DN pathophysiology that have been increasingly investigated for diagnosis, to predict disease progression or to provide efficient personal treatment. We performed a review of the literature with PubMed and Google Scholar to collect baseline data about the pathophysiology of DN and biomarkers associated. We focused our research on new and emerging biomarkers of DN. In this review, we summarized the critical signaling pathways and biological processes involved in DN and highlighted the pathogenic mediators of this disease. We next proposed a large review of the major advances that have been made in identifying new biomarkers which are more sensitive and reliable compared with currently used biomarkers. This includes information about emergent biomarkers such as functional noncoding RNAs, microRNAs, long noncoding RNAs, exosomes, and microparticles. Despite intensive strategies and constant investigation, no current single treatment has been able to reverse or at least mitigate the progression of DN, or reduce the morbidity and mortality associated with this disease. Major difficulties probably come from the renal disease being heterogeneous among the patients. Expanding the proteomics screening, including oxidative stress and inflammatory markers, along with metabolomics approaches may further improve the prognostic value and help in identifying the patients with diabetes who are at high risk of developing kidney diseases.

  17. Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway.

    PubMed

    Zhu, Liping; Han, Jiakai; Yuan, Rongrong; Xue, Lei; Pang, Wuyan

    2018-03-31

    Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood. The DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model. The fasting blood glucose level and ratio of kidney weight to body weight were measured after BBR treatment (50, 100, or 200 mg/kg) in STZ-induced DN rats. The renal injury parameters including 24-h urinary protein, blood urea nitrogen and serum creatinine were assessed. qRT-PCR was performed to detect the transcript amounts of inflammatory factors. The concentrations of inflammatory factors were evaluated by ELISA kits. Western blot analysis was conducted to measure the amounts of TLR4/NF-κB-related proteins. The apoptotic rate of podocytes was analyzed by flow cytometry using Annexin V/propidium iodide. Berberine reduced renal injury in STZ-induced DN rat model, as evidenced by the decrease in fasting blood glucose, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine, and blood urine nitrogen. BBR attenuated the systemic and renal cortex inflammatory response and inhibited TLR4/NF-κB pathway in STZ-induced DN rats and HG-induced podocytes. Also, HG-induced apoptosis of podocytes was lowered by BBR administration. Furthermore, blockade of TLR4/NF-κB pathway by resatorvid (TAK-242) or pyrrolidine dithiocarbamate aggravated the inhibitory effect of BBR on HG-induced inflammatory response and apoptosis in podocytes. Berberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.

  18. Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior.

    PubMed

    Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

    2014-03-01

    Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(-) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per⁰¹ mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per⁰¹ flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output.

  19. Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior

    PubMed Central

    Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

    2014-01-01

    Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(−) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(−) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per01 mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per01 flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

  20. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice

    PubMed Central

    Inoki, Ken; Mori, Hiroyuki; Wang, Junying; Suzuki, Tsukasa; Hong, SungKi; Yoshida, Sei; Blattner, Simone M.; Ikenoue, Tsuneo; Rüegg, Markus A.; Hall, Michael N.; Kwiatkowski, David J.; Rastaldi, Maria P.; Huber, Tobias B.; Kretzler, Matthias; Holzman, Lawrence B.; Wiggins, Roger C.; Guan, Kun-Liang

    2011-01-01

    Diabetic nephropathy (DN) is among the most lethal complications that occur in type 1 and type 2 diabetics. Podocyte dysfunction is postulated to be a critical event associated with proteinuria and glomerulosclerosis in glomerular diseases including DN. However, molecular mechanisms of podocyte dysfunction in the development of DN are not well understood. Here we have shown that activity of mTOR complex 1 (mTORC1), a kinase that senses nutrient availability, was enhanced in the podocytes of diabetic animals. Further, podocyte-specific mTORC1 activation induced by ablation of an upstream negative regulator (PcKOTsc1) recapitulated many DN features, including podocyte loss, glomerular basement membrane thickening, mesangial expansion, and proteinuria in nondiabetic young and adult mice. Abnormal mTORC1 activation caused mislocalization of slit diaphragm proteins and induced an epithelial-mesenchymal transition–like phenotypic switch with enhanced ER stress in podocytes. Conversely, reduction of ER stress with a chemical chaperone significantly protected against both the podocyte phenotypic switch and podocyte loss in PcKOTsc1 mice. Finally, genetic reduction of podocyte-specific mTORC1 in diabetic animals suppressed the development of DN. These results indicate that mTORC1 activation in podocytes is a critical event in inducing DN and suggest that reduction of podocyte mTORC1 activity is a potential therapeutic strategy to prevent DN. PMID:21606597

  1. The wnt/β-catenin signaling pathway participates in rhein ameliorating kidney injury in DN mice.

    PubMed

    Duan, Suyan; Wu, Yingyi; Zhao, Chuanyan; Chen, Mingyu; Yuan, Yanggang; Xing, Changying; Zhang, Bo

    2016-01-01

    The present study aimed to investigate the relationship between wnt/β-catenin signaling pathway and kidney impairment in diabetic nephropathy (DN) mice as well as the renoprotective effect of rhein (RH). Mice were randomly divided into four groups (n = 6): db/db mice treated with RH (DN + RH), db/db mice (DN), db/m mice treated with RH (NC + RH) and db/m mice (NC). RH-treated groups were administered orally at a daily dose 120 mg/kg. Mice were sacrificed after 12 weeks of treatments. In our study, increased albuminuria, together with weight gain and hyperglycemia was observed in the beginning of the study and continued to increase throughout the length of the study (12 weeks). Histopathologic changes were observed in the DN group. Expectedly, mice receiving the treatment with RH were protected from this injury. Meanwhile, the expression of nephrin, a podocyte-specific marker, was significantly reduced while wnt1, p-GSK-3β/tGSK-3β, p-β-catenin/tβ-catenin were higher in the DN group mice when analyzed by immunofluorescence and Western blotting. RH reversed these above changes. wnt/β-catenin signaling pathway participates in RH ameliorating kidney injury in DN mice. The manipulation of RH might act as a promising therapeutic intervention for DN.

  2. A new model of diabetic nephropathy in C57BL/6 mice challenged with advanced oxidation protein products.

    PubMed

    Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Xu, Liting; Wan, Jiao; Liu, Youhua

    2018-04-01

    There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired phenotypic characteristics. Most genetically modified mice are on the C57BL/6 background; however, they are notorious for resistance to develop DN. To overcome these conundrums, this study reports a novel DN model by challenging with advanced oxidation protein products (AOPPs) in streptozotocin-induced diabetic C57BL/6 mice. AOPPs-challenged diabetic C57BL/6 mice were more sensitive to develop progressive proteinuria, causing a 5.59-fold increase in urine albumin to creatinine ratio as compared to diabetic controls by 24 weeks. Typical lesions were present as demonstrated by significant diffuse mesangial expansion, diffuse podocyte foot process effacement, increased glomerular basement membrane thickness, focal arteriolar hyalinosis, mesangiolysis, and mild interstitial fibrosis. These changes were alleviated by losartan treatment. Collectively, these results suggest that AOPPs can accelerate the progression of DN in the resistant C57BL/6 mouse strain. Our studies offer a novel model for studying the pathogenesis of DN that resembles human diabetic kidney disease. It also makes it possible to interrogate the role of specific genetic modifications and to evaluate novel therapeutics to treat DN in preclinical setting. Copyright © 2018. Published by Elsevier Inc.

  3. A Randomized, Prospective, Parallel Group Study of Laparoscopic vs. Laparoendoscopic Single Site Donor Nephrectomy for Kidney Donation

    PubMed Central

    Aull, Meredith J.; Afaneh, Cheguevara; Charlton, Marian; Serur, David; Douglas, Melissa; Christos, Paul J.; Kapur, Sandip; Del Pizzo, Joseph J.

    2014-01-01

    Few prospective, randomized studies have assessed benefits of laparoendoscopic single site donor nephrectomy (LESS-DN) over laparoscopic donor nephrectomy (LDN). Our center initiated such a trial in January 2011, following subjects randomized to LESS-DN vs. LDN from surgery through 5 years post-donation. Subjects complete recovery/satisfaction questionnaires at 2, 6, and 12 months post-donation; transplant recipient outcomes are also recorded. 100 subjects (49 LESS-DN, 51 LDN) underwent surgery; donor demographics were similar between groups, and included a predominance of female, living unrelated donors, mean age of 47 years who underwent left donor nephrectomy. Operative parameters (overall time, time to extraction, warm ischemia time, blood loss) were similar between groups. Conversion to hand-assist laparoscopy was required in 3 LESS-DN (6.1%) vs. 2 LDN (3.9%; P=0.67). Questionnaires revealed 97.2% of LESS-DN vs. 79.5% of LDN (P=0.03) were 100% recovered by two months after donation. No significant difference was seen in satisfaction scores between the groups. Recipient outcomes were similar between groups. Our randomized trial comparing LESS donor nephrectomy to LDN confirms that LESS-DN offers a safe alternative to conventional LDN in terms of intra- and post-operative complications. LDN and LESS-DN offer similar recovery and satisfaction after donation. PMID:24934732

  4. Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

    PubMed Central

    Nakagawa, Kouki; Hayao, Keishi; Yotani, Kengo; Ogita, Futoshi; Yamamoto, Noriaki; Onishi, Hideaki

    2017-01-01

    The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES) on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP) immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON), denervation (DN), and denervation with direct ES (DN + ES). Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA), and capillary-to-fiber (C/F) ratio of the tibialis anterior (TA) muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs. PMID:28497057

  5. Association of lipoprotein lipase S447X, apolipoprotein E exon 4, and apoC3 -455T>C polymorphisms on the susceptibility to diabetic nephropathy.

    PubMed

    Ng, M C Y; Baum, L; So, W-Y; Lam, V K L; Wang, Y; Poon, E; Tomlinson, B; Cheng, S; Lindpaintner, K; Chan, J C N

    2006-07-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. In DN patients, triglyceride (TG) level is elevated and lipoprotein lipase (LPL) activity, which hydrolyzes TG, is decreased. The LPL S447X and apolipoprotein E (APOE) exon 4 polymorphisms affect TG levels, and the APOC3 -455T>C polymorphism affects LPL activity. Our aim was to examine the association of these polymorphisms with nephropathy in type 2 diabetes. We examined these polymorphisms in a case-control study of type 2 diabetic patients including 374 with DN and 392 without DN. LPL 447X-containing genotypes (447X+) were significantly decreased in DN patients [18.6 vs 25.6%, odds ratio (OR) = 0.66, p = 0.02], as were APOE epsilon3/epsilon3 genotypes (64.8 vs 73.1%, OR = 0.68, p = 0.01). In addition, combinations of genotypes [APOE epsilon3/epsilon3 and LPL 447X+ (OR = 0.56), APOC3 CC and LPL 447X+ (OR = 0.31), APOE epsilon3/epsilon3 and APOC3 CC (OR = 0.61] were protective for DN compared with the most common combination of the respective polymorphisms. Our findings suggest the importance of interactions among lipid genes in modulating the risk of DN.

  6. Management of diabetic nephropathy: Recent progress and future perspective.

    PubMed

    Ahmad, Jamal

    2015-01-01

    Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD) affecting ∼20-30% diabetics, is associated with increased cardiovascular mortality. The progression of kidney disease in patients with diabetes can take many years. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Hyperglycaemia, hypertension, and genetic pre-disposition are the main risk factors besides elevated serum lipids, smoking habits, and the amount of dietary proteins. Interventions such as glycaemic control, blood pressure control and inhibition of the renin-angiotensin-aldosterone system have been shown to slow this progression. Despite the implementation of these strategies, the number of patients with diabetes that ultimately develop end-stage renal disease remains high. The treatment of DN, therefore, has posed a formidable challenge besides optimization of renin-angiotensin-aldosterone system blockade in patients with DN; additional investigation has focused on the potential of novel therapies that target various pathways upregulated by hyperglycaemia or other targets believed to promote the progression of DN such as oxidative stress, inflammation, endothelin system and vitamin D receptors. This review article addresses the pathogenesis and some of the well established principles regarding the progression and accepted management of DN, and also includes the perspectives of novel anti-DN agents and the future directions for the prevention of DN. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  7. Designing mid-wave infrared (MWIR) thermo-optic coefficient (dn/dT) in chalcogenide glasses

    NASA Astrophysics Data System (ADS)

    Gleason, Benn; Sisken, Laura; Smith, Charmayne; Richardson, Kathleen

    2016-05-01

    Seventeen infrared-transmitting GeAsSe chalcogenide glasses were fabricated to determine the role of chemistry and structure on mid-wave infrared (MWIR) optical properties. The refractive index and thermoptic coefficients of samples were measured at λ = 4.515 μm using an IR-modified Metricon prism coupler, located at University of Central Florida. Thermo-optic coefficient (dn/dT) values were shown to range from approximately -40 ppm/°C to +65 ppm/°C, and refractive index was shown to vary between approximately 2.5000 and 2.8000. Trends in refractive index and dn/dT were found to be related to the atomic structures present within the glassy network, as opposed to the atomic percentage of any individual constituent. A linear correlation was found between the quantity (n-3•dn/dT) and the coefficient of thermal expansion (CTE) of the glass, suggesting the ability to compositionally design chalcogenide glass compositions with zero dn/dT, regardless of refractive index or dispersion performance. The tunability of these novel glasses offer increased thermal and mechanical stability as compared to the current commercial zero dn/dT options such as AMTIR-5 from Amorphous Materials Inc. For IR imaging systems designed to achieve passive athermalization, utilizing chalcogenide glasses with their tunable ranges of dn/dT (including zero) can be key to addressing system size, weight, and power (SWaP) limitations.

  8. Comparison of Biocorrosion due to Desulfovibrio desulfuricans and Desulfotomaculum nigrificans Bacteria

    NASA Astrophysics Data System (ADS)

    Lata, Suman; Sharma, Chhaya; Singh, Ajay K.

    2013-02-01

    One observes several species of sulfate-reducing bacteria in nature. Presence of these species in a media may cause microbial influenced corrosion (MIC) of materials differently. To investigate this aspect of MIC, corrosion tests were performed on three types of stainless steels. The tests were done in modified Baar's media inoculated separately by the two species of SRB namely Desulfovibrio desulfuricans (DD) and Desulfotomaculum nigrificans (DN). Electrochemical and immersion tests were performed to assess the extent of uniform and localized corrosion of these steels. Biofilms formed on the corroded samples were analyzed for estimating various components of its extracellular polymeric substances. Hydrogenase enzyme of these bacteria was tested to determine its nature and activity. Higher degree of corrosivity was observed in case of media inoculated with DD as compared to DN. More active nature of hydrogenase enzyme, its location in the periplasmic phase in DD and higher fraction of carbohydrate in biofilm formed due to DD have been suggested to be responsible for higher degree of corrosivity caused by them.

  9. Enhanced catalyst and process for converting synthesis gas to liquid motor fuels

    DOEpatents

    Coughlin, Peter K.

    1986-01-01

    The conversion of synthesis gas to liquid molar fuels by means of a cobalt Fischer-Tropsch catalyst composition is enhanced by the addition of molybdenum, tungsten or a combination thereof as an additional component of said composition. The presence of the additive component increases the olefinic content of the hydrocarbon products produced. The catalyst composition can advantageously include a support component, such as a molecular sieve, co-catalyst/support component or a combination of such support components.

  10. Non-noble metal based electro-catalyst compositions for proton exchange membrane based water electrolysis and methods of making

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

    Kumta, Prashant N.; Kadakia, Karan Sandeep; Datta, Moni Kanchan

    The invention provides electro-catalyst compositions for an anode electrode of a proton exchange membrane-based water electrolysis system. The compositions include a noble metal component selected from the group consisting of iridium oxide, ruthenium oxide, rhenium oxide and mixtures thereof, and a non-noble metal component selected from the group consisting of tantalum oxide, tin oxide, niobium oxide, titanium oxide, tungsten oxide, molybdenum oxide, yttrium oxide, scandium oxide, cooper oxide, zirconium oxide, nickel oxide and mixtures thereof. Further, the non-noble metal component can include a dopant. The dopant can be at least one element selected from Groups III, V, VI and VIImore » of the Periodic Table. The compositions can be prepared using a surfactant approach or a sol gel approach. Further, the compositions are prepared using noble metal and non-noble metal precursors. Furthermore, a thin film containing the compositions can be deposited onto a substrate to form the anode electrode.« less

  11. 30 CFR 77.1304 - Blasting agents; special provisions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ammonium nitrate blasting agents, and the components thereof prior to mixing, shall be mixed and stored in... Sensitized Ammonium Nitrate Blasting Agents,” or subsequent revisions. (b) Where pneumatic loading is...

  12. 30 CFR 77.1304 - Blasting agents; special provisions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ammonium nitrate blasting agents, and the components thereof prior to mixing, shall be mixed and stored in... Sensitized Ammonium Nitrate Blasting Agents,” or subsequent revisions. (b) Where pneumatic loading is...

  13. 30 CFR 77.1304 - Blasting agents; special provisions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ammonium nitrate blasting agents, and the components thereof prior to mixing, shall be mixed and stored in... Sensitized Ammonium Nitrate Blasting Agents,” or subsequent revisions. (b) Where pneumatic loading is...

  14. Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice

    PubMed Central

    Yan, Jian; Ginsberg, Stephen D.; Powers, Brian; Alldred, Melissa J.; Saltzman, Arthur; Strupp, Barbara J.; Caudill, Marie A.

    2014-01-01

    Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a trisomic mouse model of Down syndrome and Alzheimer's disease. To gain insight into the mechanisms underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters choline metabolism in adult Ts65Dn offspring. Deuterium-labeled methyl-d9-choline was administered to adult Ts65Dn and disomic (2N) female littermates born to choline-unsupplemented or choline-supplemented Ts65Dn dams. Enrichment of d9-choline metabolites (derived from intact choline) and d3 + d6-choline metabolites [produced when choline-derived methyl groups are used by phosphatidylethanolamine N-methyltransferase (PEMT)] was measured in harvested tissues. Adult offspring (both Ts65Dn and 2N) of choline-supplemented (vs. choline-unsupplemented) dams exhibited 60% greater (P≤0.007) activity of hepatic PEMT, which functions in de novo choline synthesis and produces phosphatidylcholine (PC) enriched in docosahexaenoic acid. Higher (P<0.001) enrichment of PEMT-derived d3 and d6 metabolites was detected in liver, plasma, and brain in both genotypes but to a greater extent in the Ts65Dn adult offspring. MCS also yielded higher (P<0.05) d9 metabolite enrichments in liver, plasma, and brain. These data demonstrate that MCS exerts lasting effects on offspring choline metabolism, including up-regulation of the hepatic PEMT pathway and enhanced provision of choline and PEMT-PC to the brain.—Yan, J., Ginsberg, S. D., Powers, B., Alldred, M. J., Saltzman, A., Strupp, B. J., Caudill, M. A. Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice. PMID:24963152

  15. Occurrence and risk assessment of phthalate esters (PAEs) in vegetables and soils of suburban plastic film greenhouses.

    PubMed

    Wang, Jun; Chen, Gangcai; Christie, Peter; Zhang, Manyun; Luo, Yongming; Teng, Ying

    2015-08-01

    Phthalate esters (PAEs) are suspected of having adverse effects on human health and have been frequently detected in soils and vegetables. The present study investigated their occurrence and composition in plastic film greenhouse soil-vegetable systems and assessed their potential health risks to farmers exposed to these widespread pollutants. Six priority control phthalates, namely dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP), were determined in 44 plastic film greenhouse vegetables and corresponding soils. Total PAEs ranged from 0.51 to 7.16mgkg(-1) in vegetables and 0.40 to 6.20mgkg(-1) in soils with average concentrations of 2.56 and 2.23mgkg(-1), respectively. DnBP, DEHP and DnOP contributed more than 90% of the total PAEs in both vegetables and soils but the proportions of DnBP and DnOP in vegetables were significantly (p<0.05) higher than in soils. The average concentrations of PAEs in pot herb mustard, celery and lettuce were >3.00mgkg(-1) but were <2.50mgkg(-1) in the corresponding soils. Stem and leaf vegetables accumulated more PAEs. There were no clear relationships between vegetable and soil PAEs. Risk assessment indicates that DnBP, DEHP and DnOP exhibited elevated non-cancer risk with values of 0.039, 0.338 and 0.038, respectively. The carcinogenic risk of DEHP was about 3.94×10(-5) to farmers working in plastic film greenhouses. Health risks were mainly by exposure through vegetable consumption and soil ingestion. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease.

    PubMed

    Passos, Lívia Silva Araújo; Villani, Fernanda Nobre Amaral; Magalhães, Luísa Mourão Dias; Gollob, Kenneth J; Antonelli, Lis Ribeiro do Vale; Nunes, Maria Carmo Pereira; Dutra, Walderez Ornelas

    2016-09-15

    The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon γ (IFN-γ) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN-γ by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. Functional characterization of DnSIZ1, a SIZ/PIAS-type SUMO E3 ligase from Dendrobium.

    PubMed

    Liu, Feng; Wang, Xiao; Su, Mengying; Yu, Mengyuan; Zhang, Shengchun; Lai, Jianbin; Yang, Chengwei; Wang, Yaqin

    2015-09-17

    SUMOylation is an important post-translational modification of eukaryotic proteins that involves the reversible conjugation of a small ubiquitin-related modifier (SUMO) polypeptide to its specific protein substrates, thereby regulating numerous complex cellular processes. The PIAS (protein inhibitor of activated signal transducers and activators of transcription [STAT]) and SIZ (scaffold attachment factor A/B/acinus/PIAS [SAP] and MIZ) proteins are SUMO E3 ligases that modulate SUMO conjugation. The characteristic features and SUMOylation mechanisms of SIZ1 protein in monocotyledon are poorly understood. Here, we examined the functions of a homolog of Arabidopsis SIZ1, a functional SIZ/PIAS-type SUMO E3 ligase from Dendrobium. In Dendrobium, the predicted DnSIZ1 protein has domains that are highly conserved among SIZ/PIAS-type proteins. DnSIZ1 is widely expressed in Dendrobium organs and has a up-regulated trend by treatment with cold, high temperature and wounding. The DnSIZ1 protein localizes to the nucleus and shows SUMO E3 ligase activity when expressed in an Escherichia coli reconstitution system. Moreover, ectopic expression of DnSIZ1 in the Arabidopsis siz1-2 mutant partially complements several phenotypes and results in enhanced levels of SUMO conjugates in plants exposed to heat shock conditions. We observed that DnSIZ1 acts as a negative regulator of flowering transition which may be via a vernalization-induced pathway. In addition, ABA-hypersensitivity of siz1-2 seed germination can be partially suppressed by DnSIZ1. Our results suggest that DnSIZ1 is a functional homolog of the Arabidopsis SIZ1 with SUMO E3 ligase activity and may play an important role in the regulation of Dendrobium stress responses, flowering and development.

  18. Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican

    PubMed Central

    Howell, Matthew D; Gottschall, Paul E

    2012-01-01

    DS (Down syndrome), resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls). In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs. In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze) and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets), an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits. PMID:22225533

  19. Unconventional Tough Double-Network Hydrogels with Rapid Mechanical Recovery, Self-Healing, and Self-Gluing Properties.

    PubMed

    Jia, Haiyan; Huang, Zhangjun; Fei, Zhaofu; Dyson, Paul J; Zheng, Zhen; Wang, Xinling

    2016-11-16

    Hydrogels are polymeric materials that have a relatively high capacity for holding water. Recently, a double network (DN) technique was developed to fabricate hydrogels with a toughness comparable to rubber. The mechanical properties of DN hydrogels may be attributed to the brittle sacrificial bonding network of one hydrogel, facilitating stress dispersion, combined with ductile polymer chains of a second hydrogel. Herein, we report a novel class of tunable DN hydrogels composed of a polyurethane hydrogel and a stronger, dipole-dipole and H-bonding interaction reinforced (DHIR) hydrogel. Compared to conventional DN hydrogels, these materials show remarkable improvements in mechanical recovery, modulus, and yielding, with excellent self-healing and self-gluing properties. In addition, the new DN hydrogels exhibit excellent tensile and compression strengths and possess shape-memory properties, which make them promising for applications in engineering, biomedicine, and other domains where load bearing is required.

  20. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome

    PubMed Central

    Holtzman, David M.; Santucci, Daniela; Kilbridge, Joshua; Chua-Couzens, Jane; Fontana, David J.; Daniels, Scott E.; Johnson, Randolph M.; Chen, Karen; Sun, Yuling; Carlson, Elaine; Alleva, Enrico; Epstein, Charles J.; Mobley, William C.

    1996-01-01

    To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain. PMID:8917591

  1. Effect of Refractive Index Variation on Two-Wavelength Interferometry for Fluid Measurements

    NASA Technical Reports Server (NTRS)

    Mercer, Carolyn R.

    1998-01-01

    Two wavelength interferometry can in principle be used to measure changes in both temperature and concentration in a fluid, but measurement errors may be large if the fluid dispersion is small. This paper quantifies the effects of uncertainties in dn/dT and dn/dC on the measured temperature and concentration when using the simple expression dn = (dn/dT)dT + (dn/dC)dC. For the data analyzed here, ammonium chloride in water from -5 to 10(exp infinity) C over a concentration range of 2-14% and for wavelengths 514.5 and 633 nm, it is shown that the gradients must be known to within 0.015% to produce a modest 10% uncertainty in the measured temperature and concentration. These results show that real care must be taken to ensure the accuracy of refractive index gradients when using two wavelength interferometry for the simultaneous measurement of temperature and concentration.

  2. Accommodation by Varying Strain Regimes along the Northern Luzon Arc (Coastal Range, Taiwan) - Insights from Focal Mechanism Strain Inversions

    NASA Astrophysics Data System (ADS)

    O'Hara, D.; Lee, J.; Lewis, J. C.; Rau, R.

    2013-12-01

    Taiwan is the product of modern subduction polarity reversal coupled with arc-continent collision. The NW-moving Philippine Sea plate (PSP) subducts beneath the Eurasian plate (EUR) to the northeast of Taiwan at the Ryukyu trench, while overriding EUR south of Taiwan at the Manila trench, bringing the Luzon volcanic arc into collision with the deforming sediments of the Eurasian passive margin. The obliquity between the N-S trending Luzon Arc (LA) and NE-SW trending passive margin is causing the southward, temporal propagation of collision since ~6 Ma. The collided forearc and clastic sediments accreted by the advancing arc created the Coastal Range (CR), whose western-most extent lies at the suture zone between the two plates, the NNE-SSW trending Longitudinal Valley Fault (LVF). In order to understand the change in stress along the northern LA as it docks onto EUR, we inverted over 1900 relocated earthquake focal mechanism solutions within the on-land CR and offshore LA regions for spatial strain tensors. The focal mechanisms cover seismicity from 1991-2013, ranging in depths 0-112 km and magnitudes 2.22-6.92. For our analyses, we grouped the focal mechanisms based on 15' Latitudinal intervals along the study area and inverted the data for best-fit strain tensors using a micropolar continuum model of crustal deformation. Results suggest dominant compression in all regions with accommodation occurring through oblique reverse faults of varying dips. Trends of σ1 rotate clockwise (CW) from 100° in the south to 155° in the north. This CW rotation is also observed in the preferred nodal plane slip vector trends - from E-W orientation in the south to NW-SE in the north. The rotation of σ1 and slip vector trends creates varying degrees of obliquity with the direction normal (DN) to CR (112°). The trends in the southern part of the study area show obliquity counterclockwise (CCW) to DN; trends in the central part are near parallel to DN; and trends in the northern part show obliquity CW to DN. GPS vectors from 2008-2012 using an ITRF reference frame show similar changes in obliquity with GPS velocity trends oblique CCW and CW to DN in the southern and northern areas, respectively, and near parallel to DN in the central area. Our results suggest the accommodation of three varying strain regimes along the northern LA (CR) system - (1) strain partitioning within the Manila forearc basin due to the obliquity between N-S trending LA and NW trending convergence vector; (2) convergence-related strain in the central LVF and CR along NNE trending major thrust faults with a small oblique component due to the obliquity between DN and the convergence vector; and (3) strain partitioning along the Ryukyu trench and forearc basin due to the obliquity between northward subducting plate along the WNW- ESE trending Ryukyu trench and NW convergence vector. As a result, the different subducting characteristics of strain regimes correspond to the different stages of arc accretion/collision, from south to north: pre-collision, present collision, waning collision, and subduction.

  3. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy

    PubMed Central

    Reed, Sarah A.; Sandesara, Pooja B.; Senf, Sarah M.; Judge, Andrew R.

    2012-01-01

    Cachexia is characterized by inexorable muscle wasting that significantly affects patient prognosis and increases mortality. Therefore, understanding the molecular basis of this muscle wasting is of significant importance. Recent work showed that components of the forkhead box O (FoxO) pathway are increased in skeletal muscle during cachexia. In the current study, we tested the physiological significance of FoxO activation in the progression of muscle atrophy associated with cachexia. FoxO-DNA binding dependent transcription was blocked in the muscles of mice through injection of a dominant negative (DN) FoxO expression plasmid prior to inoculation with Lewis lung carcinoma cells or the induction of sepsis. Expression of DN FoxO inhibited the increased mRNA levels of atrogin-1, MuRF1, cathepsin L, and/or Bnip3 and inhibited muscle fiber atrophy during cancer cachexia and sepsis. Interestingly, during control conditions, expression of DN FoxO decreased myostatin expression, increased MyoD expression and satellite cell proliferation, and induced fiber hypertrophy, which required de novo protein synthesis. Collectively, these data show that FoxO-DNA binding-dependent transcription is necessary for normal muscle fiber atrophy during cancer cachexia and sepsis, and further suggest that basal levels of FoxO play an important role during normal conditions to depress satellite cell activation and limit muscle growth.—Reed, S. A., Sandesara, P. B., Senf, S. F., Judge, A. R. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. PMID:22102632

  4. 22 CFR 215.13 - General exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... primary functions of USAID are not of a law enforcement nature, the mandate to ensure USAID funding is not... component thereof which performs as its principal function any activity pertaining to the enforcement of...

  5. 22 CFR 215.13 - General exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... primary functions of USAID are not of a law enforcement nature, the mandate to ensure USAID funding is not... component thereof which performs as its principal function any activity pertaining to the enforcement of...

  6. 22 CFR 215.13 - General exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... primary functions of USAID are not of a law enforcement nature, the mandate to ensure USAID funding is not... component thereof which performs as its principal function any activity pertaining to the enforcement of...

  7. 22 CFR 215.13 - General exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... primary functions of USAID are not of a law enforcement nature, the mandate to ensure USAID funding is not... component thereof which performs as its principal function any activity pertaining to the enforcement of...

  8. 22 CFR 215.13 - General exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... primary functions of USAID are not of a law enforcement nature, the mandate to ensure USAID funding is not... component thereof which performs as its principal function any activity pertaining to the enforcement of...

  9. Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer Prevention

    DTIC Science & Technology

    2013-05-01

    epigallocatechin-3-gallate. Cancer Res. 2009;69:1712-6. 2. Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H. Oral infusion of pomegranate fruit ...and fungi , and is also known for its non-toxic, non-immunogenic properties (23). It has already been used as a pharmaceutical excipient, a weight loss...component EGCG and perceived toxicity associated with its long-term use affect its clinical outcome (36,37). This study suggests a different

  10. Roles of FGFR3 during morphogenesis of Meckel's cartilage and mandibular bones

    PubMed Central

    Havens, Bruce A.; Velonis, Dimitris; Kronenberg, Mark S.; Lichtler, Alex C.; Oliver, Bonnie; Mina, Mina

    2008-01-01

    To address the functions of FGFR2 and FGFR3 signaling during mandibular skeletogenesis, we over-expressed in the developing chick mandible, replication-competent retroviruses carrying truncated FGFR2c or FGFR3c that function as dominant negative receptors (RCAS-dnFGFR2 and RCAS-dnFGFR3). Injection of RCAS-dnFGFR3 between HH15−20 led to reduced proliferation, increased apoptosis, and decreased differentiation of chondroblasts in Meckel's cartilage. These changes resulted in the formation of a hypoplastic mandibular process and truncated Meckel's cartilage. This treatment also affected the proliferation and survival of osteoprogenitor cells in osteogenic condensations, leading to the absence of five mandibular bones on the injected side. Injection of RCAS-dnFGFR2 between HH15−20 or RCAS-dnFGFR3 at HH26 did not affect the morphogenesis of Meckel's cartilage but resulted in truncations of the mandibular bones. RCAS-dnFGFR3 affected the proliferation and survival of the cells within the periosteum and osteoblasts. Together these results demonstrate that FGFR3 signaling is required for the elongation of Meckel's cartilage and FGFR2 and FGFR3 have roles during intramembranous ossification of mandibular bones. PMID:18339367

  11. Inhibitory Effects of 4'-Demethylnobiletin, a Metabolite of Nobiletin, on 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Inflammation in Mouse Ears.

    PubMed

    Wu, Xian; Song, Mingyue; Rakariyatham, Kanyasiri; Zheng, Jinkai; Wang, Minqi; Xu, Fei; Gao, Zili; Xiao, Hang

    2015-12-30

    Nobiletin (NOB) is major citrus flavonoid with many health-promoting benefits. We reported previously that 4'-demethylnobiletin (4DN), a major metabolite of NOB, significantly inhibited lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 macrophages. In this study, we further studied the anti-inflammatory effects of 4DN in TPA-induced skin inflammation in mice. We demonstrated that topical application of 4DN decreased TPA-induced ear edema by >88 ± 4.77% in mice. This inhibitory effect was associated with inhibition on TPA-induced up-regulation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Immunoblotting results showed that 4DN resulted in profound effects on multiple proteins related with inflammation and carcinogenesis. 4DN significantly decreased the expression levels of iNOS, COX-2, and MMP-9, suppressed phosphorylation of PI3K/Akt and ERK, and increased the levels of HO-1 and NQO1 in TPA-treated mice. Overall, the results demonstrated that 4DN had strong anti-inflammatory effects in vivo, which provided a scientific basis for using NOB to inhibit inflammation-driven diseases.

  12. Benefit of magnesium-25 carrying porphyrin-fullerene nanoparticles in experimental diabetic neuropathy

    PubMed Central

    Hosseini, Asieh; Sharifzadeh, Mohammad; Rezayat, Seyed Mahdi; Hassanzadeh, Gholamreza; Hassani, Shokoufeh; Baeeri, Maryam; Shetab-Bushehri, Vahid; Kuznetsov, Dmitry A; Abdollahi, Mohammad

    2010-01-01

    Diabetic neuropathy (DN) is a debilitating disorder occurring in most diabetic patients without a viable treatment yet. The present work examined the protective effect of 25Mg-PMC16 nanoparticle (porphyrin adducts of cyclohexil fullerene-C60) in a rat model of streptozotocin (STZ)-induced DN. 25Mg-PMC16 (0.5 lethal dose50 [LD50]) was administered intravenously in two consecutive days before intraperitoneal injection of STZ (45 mg/kg). 24Mg-PMC16 and MgCl2 were used as controls. Blood 2,3-diphosphoglycerate (2,3-DPG), oxidative stress biomarkers, adenosine triphosphate (ATP) level in dorsal root ganglion (DRG) neurons were determined as biomarkers of DN. Results indicated that 2,3-DPG and ATP decreased whereas oxidative stress increased by induction of DN which all were improved in 25Mg-PMC16-treated animals. No significant changes were observed by administration of 24Mg-PMC16 or MgCl2 in DN rats. It is concluded that in DN, oxidative stress initiates injuries to DRG neurons that finally results in death of neurons whereas administration of 25Mg-PMC16 by release of Mg and increasing ATP acts protectively. PMID:20957114

  13. 78 FR 70888 - Need for Agency Approval of a Railroad's Use of Certain Technology That Has Been Previously...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-27

    ... technologies, namely safety-critical processor-based signal or train control systems, including subsystems and... or train control system (including a subsystem or component thereof) that was in service as of June 6... processor-based signal or train control system, subsystem, or component.'' See 49 CFR 236.903. Under Subpart...

  14. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

    PubMed Central

    O'Leary, Jacqueline G.; Samaniego, Millie; Barrio, Marta Crespo; Potena, Luciano; Zeevi, Adriana; Djamali, Arjang; Cozzi, Emanuele

    2016-01-01

    Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance. PMID:26680372

  15. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2014-05-27

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  16. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2014-10-28

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  17. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2015-04-14

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  18. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2013-10-01

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  19. Evaluation of Populus and Salix continuously irrigated with landfill leachate I. Genotype-specific elemental phytoremediation

    Treesearch

    Ronald S., Jr. Zalesny; Edmund O. Bauer

    2007-01-01

    There is a need for the identification and selection of specific tree genotypes that can sequester elements from contaminated soils, with elevated rates of uptake. We irrigated Populus (DN17, DN182, DN34, NM2, NM6) and Salix (94003, 94012, S287, S566, SX61) genotypes planted in large soil-filled containers with landfill leachate or...

  20. Evaluation of Populus and Salix continuously irrigated with landfill leachate II. Soils and early tree development

    Treesearch

    Ronald S., Jr. Zalesny; Edmund O. Bauer

    2007-01-01

    Soil contaminant levels and early tree growth data are helpful for assessing phytoremediation systems. Populus (DN17, DN182, DN34, NM2, and NM6) and Salix (94003, 94012, S287, S566, and SX61) genotypes were irrigated with landfill leachate or municipal water and tested for differences in 1) element concentrations (P, K, Ca, Mg, S,...

  1. An Automatic Drag-and-Drop Assistive Program Developed to Assistive People with Developmental Disabilities to Improve Drag-and-Drop Efficiency

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang; Huang, Hsun-Chin; Liao, Yung-Kun; Shih, Ching-Tien; Chiang, Ming-Shan

    2010-01-01

    The latest researches adopted software technology to improve pointing performance; however, Drag-and-Drop (DnD) operation is also commonly used in modern GUI programming. This study evaluated whether two children with developmental disabilities would be able to improve their DnD performance, through an Automatic DnD Assistive Program (ADnDAP). At…

  2. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

    PubMed Central

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice. PMID:26973453

  3. 77 FR 5568 - Certain Muzzle-Loading Firearms and Components Thereof Determination Not To Review an Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... and Bergara Barrels Europe, both of Bergara, Spain (collectively ``the BPI respondents''). The... to only respondents Ardesa Firearms (Ardesa) of Zamudio-Vizcaya, Spain and Traditional Sporting Goods...

  4. 82 FR 35991 - Certain Flash Memory Devices and Components Thereof; Notice of Commission Determination Not To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2017-08-02

    ... following respondents: SanDisk LLC of Milpitas, California; Western Digital Corporation of Irvine, California; Western Digital Technologies, Inc. of Milpitas, California; SanDisk Limited of Yokohama, Japan...

  5. 76 FR 52969 - In the Matter of Certain Protective Cases and Components Thereof Notice of Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    .... International Trade Commission has determined not to review the presiding administrative law judge's (``ALJ... named twenty nine respondents, including Cellaris Franchise, Inc. of Alpharetta, Georgia (``Cellaris...

  6. 77 FR 2757 - Certain Electric Fireplaces, Components Thereof, Manuals for Same, Certain Processes for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-19

    ..., misappropriation of trade secrets, breach of contract, and tortious interference with contract. The complaint... by reason of misappropriation of trade secrets, breach of contract, or tortious interference with...

  7. 75 FR 62565 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and..., portable music and data processing devices, computers and components thereof. The complaint names as...

  8. 75 FR 7571 - Notice of Intent To Grant Exclusive Patent License; Applied Minerals, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-22

    ..., lumber, chipboard, and ceiling tile; and caulks, sealants and adhesives; and high pressure laminates, wall, counter top and floor coverings or components thereof; and ceramics, cultured marbles, and tiles...

  9. 75 FR 5290 - Notice of Intent To Grant Exclusive Patent License; Applied Minerals, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-02

    ..., lumber, chipboard, and ceiling tile; and caulks, sealants and adhesives; and high pressure laminates, wall, counter top and floor coverings or components thereof; and ceramics, cultured marbles, and tiles...

  10. The curious case of SN 2011dn: A very peculiar type Ia supernova?

    NASA Astrophysics Data System (ADS)

    Rachubo, Alisa

    Type Ia supernovae (SNe Ia) are excellent cosmological distance indicators due to the uniformity in their light curves, which led to the major discovery of the accelerated expansion of the universe. However, SNe Ia are not so uniform as one may expect, as there are many peculiar SNe Ia that exhibit differences in their photometric and spectroscopic behavior from normal SNe Ia. One of the goals of supernova cosmology today is to produce a cleaner sample of SNe Ia without these peculiar SNe Ia. Here we consider SN 2011dn, a peculiar SN Ia candidate. In 2011, Salvo, et al. carried out a preliminary analysis of a subset of the data prescribed here, and identified spectral and photometric peculiarities in this object's evolution that warranted further analysis. Here, we present a complete re-reduction and reanalysis of B, V,R, and I photometry of SN 2011dn obtained at Mount Laguna Observatory, spanning from 7 days before maximum light in B to 88 days past maximum light. In addition, we also consider total flux spectra from 9 days before maximum light to 4 days after maximum light, along with ultraviolet (UV) photometry obtained with the Swift telescope. From SN 2011dn's optical spectra, we find that SN 2011dn most closely resembles a SN 1991T-like type Ia supernova ('91T-like SN Ia). Such SNe Ia are typically more luminous than normal SNe Ia, and possess broader (i.e., they decline less rapidly than normal from maximum light) light curves. Their Deltam15(B) (drop in B magnitude 15 days after maximum light) are typically significantly less than the canonical value of 1.1, and can be as low as 0.8. In the earlier preliminary analysis, Salvo et al. measured a surprisingly high Deltam15(B) value for SN 2011dn, of ˜ 1.1. Since SN 2011dn was embedded in UGC 11501 (its host galaxy), however, it is possible that some of the light from the host galaxy was included in the photometric aperture, resulting in inaccurate photometric measurements. Here, in order to better isolate the supernova light from its host galaxy, we employ galaxy-subtraction techniques to generate more precise light curves. From these data, we obtain an updated Deltam15( B) value of 1.01 +/- 0.02, which suggests that SN 2011dn is indeed slightly overluminous compared to normal SNe Ia, but perhaps not as overluminous as '91T-like SNe Ia. However, despite this apparent resolution of the spectral and photometric conflict, we find SN 2011dn to still exhibit some unique features. For instance, its near-maximum and especially its post-maximum spectra exhibit an unusually weak Si II lambda6355 feature, even considering that '91T-like SNe Ia spectra tend to have shallow silicon features. Furthermore, we find that SN 2011dn exhibits some unusual UV-optical color evolution, though its early-time UV excess may be linked to unburned carbon in SN 2011dn's ejecta, as indicated by the C III lambda4649 feature in its pre-maximum spectra. Altogether, after a careful reanalysis of the spectral and photometric properties of SN 2011dn, we classify it as slightly overluminous, with '91T-like pre-maximum and near-maximum spectra, but exhibiting some atypical features. SN 2011dn is not as peculiar as anticipated, but still has some characteristics that are unique to it.

  11. The relationship between solar keratoses and squamous cell carcinomas among Japanese.

    PubMed

    Takemiya, M; Ohtsuka, H; Miki, Y

    1990-06-01

    Between 1976 and 1988, 135 patients with solar keratosis (SK) and 53 patients with squamous cell carcinoma (SCC) on the sun-exposed skin, but without apparent preceding diseases such as burn scars, chronic radiodermatitis, chronic arsenic poisoning, or xeroderma pigmentosum, were encountered. Sixteen of the SCC patients also had SK on other areas of sun-exposed skin. There were 31 SCC patients also showing SK (SK-SCC) and 22 SCC not showing SK (DN-SCC) within the same histologic sections. The mean ages of the patients with SK-SCC and with DN-SCC were similar. Metastases to regional lymph nodes were observed in 5 SK-SCC patients, of whom 3 died of the disease, and in 5 DN-SCC patients, of whom 4 died of the disease. The five-year post-operative survival rates were 70% in SK-SCC and 74% in DN-SCC; the ten-year post-operative survival rates were 70% in SK-SCC and 44% in DN-SCC.

  12. Mexican humanitarian assistance system.

    DTIC Science & Technology

    2016-05-26

    Stabilization Mission in Haiti, SEDENA, Plan-DN-III- E , international relief system, Cluster system, Organization of American States, Conference of American...strategic plan for disaster relief—Plan DN-III- E . The plan contains annexes with specific instructions to different military actors and, because of...2FSArticuloSinPaginaLayout. 9 “Gaceta Parlamentaria 22 Apr 2010.” 10 Estado Mayor Defensa Nacional, Plan DN-III- E : Auxilio a La Poblacion Civil En Casos

  13. Child dental neglect: is it a neglected area in the UK?

    PubMed

    Sarri, G; Marcenes, W

    2012-08-01

    This commentary focuses on the condition of dental neglect (DN) in children in the UK. It is divided into three sections: the first section defines DN in children and its consequences, the second section discusses who may be responsible for dental diseases in children as a result of neglect and the third section proposes a holistic approach to address DN in children in the UK.

  14. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    PubMed Central

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

    Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

  15. Silencing of Histone Deacetylase 9 Expression in Podocytes Attenuates Kidney Injury in Diabetic Nephropathy

    PubMed Central

    Liu, Feng; Zong, Ming; Wen, Xiaofei; Li, Xuezhu; Wang, Jun; Wang, Yi; Jiang, Wei; Li, Xiaojun; Guo, Zhongliang; Qi, Hualin

    2016-01-01

    Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN. Secondly, knockdown of HDAC9 in mouse podocytes significantly suppressed HG-induced reactive oxygen species (ROS) generation, cell apoptosis and inflammation through JAK2/STAT3 pathway and reduced the podocytes injury by decreasing the expression levels of Nephrin and Podocin. Moreover, in diabetic db/db mice, silencing of HDAC9 attenuated the glomerulosclerosis, inflammatory cytokine release, podocyte apoptosis and renal injury. Collectively, these data indicate that HDAC9 may be involved in the process of DN, especially podocyte injury. Our study suggest that inhibition of HDAC9 may have a therapeutic potential in DN treatment. PMID:27633396

  16. Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice.

    PubMed

    Iismaa, Siiri E; Li, Ming; Kesteven, Scott; Wu, Jianxin; Chan, Andrea Y; Holman, Sara R; Calvert, John W; Haq, Ahtesham Ul; Nicks, Amy M; Naqvi, Nawazish; Husain, Ahsan; Feneley, Michael P; Graham, Robert M

    2018-04-17

    We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W v mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI) due to coronary artery ligation are improved in this transgenic model. Compared to non-transgenic littermates (NTLs), adult male dn-c-kit-Tg mice displayed CM hypertrophy and concentric left ventricular (LV) hypertrophy in the absence of an increase in workload. Stroke volume and cardiac output were preserved and LV wall stress was markedly lower than that in NTLs, leading to a more energy-efficient heart. In response to MI, infarct size in adult (16-week old) dn-c-kit-Tg hearts was similar to that of NTL after 24 h but was half that in NTL hearts 12 weeks post-MI. Cumulative CM cell cycle entry was only modestly increased in dn-c-kit-Tg hearts. However, dn-c-kit-Tg mice were more resistant to infarct expansion, adverse LV remodelling and contractile dysfunction, and suffered no early death from LV rupture, relative to NTL mice. Thus, pre-existing cardiac hypertrophy lowers wall stress in dn-c-kit-Tg hearts, limits infarct expansion and prevents death from myocardial rupture.

  17. Development potential of the Dauin geothermal prospect, Negros Oriental, Philippines

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

    Bayrante, L.F.; Hermoso, D.Z.; Candelaria, M.R.

    1997-12-31

    The Dauin geothermal prospect, situated 5 km southeast of the Palinpinon I and II sectors, was drilled between 1982 and 1983 to test its viability for development. Drilling results indicated that DN-1 was drilled closer to the source region than DN-2 where permeability, temperature, and alteration mineralogy were generally unpromising. DN-1 encountered temperatures of at least 240{degrees}C and a neutral-pH fluid with reservoir chloride of 3000 mg/kg. In particular, the presence of sulphur in the DN-1 discharge provoked debates and many speculation on the nature of the fluid in the area. The area was re-evaluated in 1996 for the followingmore » reasons: (1) Renewed interests on other geothermal prospects within Negros Island from an economic point of view and the success of modular plant developments are Pal II and other areas in the Philippines; (2) Reinterpretation of the genesis of sulphur contained in the DN-1 discharge fluid; (3) Encouraging temperature, permeability and neutral-pH alterations at depth and the neutral character of DN-1 discharge fluid; and (4) Reinterpretation of the hydrological model from a geochemical and geological point of view. The study indicates good potential for modular power development.« less

  18. Effects of Temperature on Chronic Trapezius Myofascial Pain Syndrome during Dry Needling Therapy

    PubMed Central

    2014-01-01

    The purpose of this study was to investigate the effects of temperature on chronic trapezius myofascial pain syndrome during dry needling therapy. Sixty patients were randomized into two groups of dry needling (DN) alone (group A) and DN combined with heat therapy group (group B). Each patient was treated once and the therapeutic effect was assessed by the visual analogue scale (VAS), pressure pain threshold (PPT), and the 36-item short form health survey (SF-36) at seven days, one month, and three months after treatment. Evaluation based on VAS and PPT showed that the pain of patients in groups A and B was significantly (P < 0.05) relieved at seven days, one month, and three months after treatment Compared to before treatment. There was significantly (P < 0.05) less pain in group B than group A at one and three months after treatment. The SF-36 evaluation demonstrated that the physical condition of patients in both groups showed significant (P < 0.05) improvement at one month and three months after treatment than before treatment. Our study suggests that both DN and DN heating therapy were effective in the treatment of trapezius MPS, and that DN heating therapy had better long-term effects than DN therapy. PMID:25383083

  19. Identification of Type VI Collagen Synthesizing Cells in Human Diabetic Glomerulosclerosis Using Renal Biopsy Sections

    PubMed Central

    Razzaque, Mohammed Shawkat; Koji, Takehiko; Harada, Takashi; Taguchi, Takashi

    1997-01-01

    Although the role of extracellular matrices in the development of glomerulosclerosis has been discussed widely, the cellular origin of type VI collagen in diabetic nephropathy (DN) has remained relatively unexplored. This study reports the distribution and cellular origin of type VI collagen in DN. Type VI collagen‐specific oligonucleotide probes and monoclonal antibody were used to assess the relative expression of mRNA for \\alpha1 (VI) chain and its translated protein in paraffin‐embedded renal biopsy sections of DN. By immunohistochemistry, compared to the control, increased deposition of type VI collagen was noted in the diffuse and nodular lesions of diabetic glomeruli. For cellular localization of type VI collagen mRNA, paraffin‐embedded renal sections of the control and DN were hybridized in situ with digoxigenin (Dig)‐labeled antisense oligo‐DNA probe complementary to a part of \\alpha1 (VI) mRNA. In comparison to the control kidney sections, increased numbers of intraglomerular cells (both mesangial and epithelial cells) were positive for α1 (VI) mRNA in renal biopsy sections of DN. From the results, we conclude that overexpression of type VI collagen by intraglomerular cells with its increased deposition might significantly contribute to the glomerulosclerosis found in DN. PMID:9497854

  20. Emotional and cognitive stimuli differentially engage the default network during inductive reasoning.

    PubMed

    Eldaief, Mark C; Deckersbach, Thilo; Carlson, Lindsay E; Beucke, Jan C; Dougherty, Darin D

    2012-04-01

    The brain's default network (DN) is comprised of several cortical regions demonstrating robust intrinsic connectivity at rest. The authors sought to examine the differential effects of emotional reasoning and reasoning under certainty upon the DN through the employment of an event-related fMRI design in healthy participants. Participants were presented with syllogistic arguments which were organized into a 2 × 2 factorial design in which the first factor was emotional salience and the second factor was certainty/uncertainty. We demonstrate that regions of the DN were activated both during reasoning that is emotionally salient and during reasoning which is more certain, suggesting that these processes are neurally instantiated on a network level. In addition, we present evidence that emotional reasoning preferentially activates the dorsomedial (dMPFC) subsystem of the DN, whereas reasoning in the context of certainty activates areas specific to the DN's medial temporal (MTL) subsystem. We postulate that emotional reasoning mobilizes the dMPFC subsystem of the DN because this type of reasoning relies upon the recruitment of introspective and self-relevant data such as personal bias and temperament. In contrast, activation of the MTL subsystem during certainty argues that this form of reasoning involves the recruitment of mnemonic and semantic associations to derive conclusions.

  1. Characterization of the Interactions between Titanium Dioxide Nanoparticles and Polymethoxyflavones Using Surface-Enhanced Raman Spectroscopy.

    PubMed

    Cao, Xiaoqiong; Ma, Changchu; Gao, Zili; Zheng, Jinkai; He, Lili; McClements, David Julian; Xiao, Hang

    2016-12-14

    Nanosized titanium dioxide (TiO 2 ) particles are commonly present in TiO 2 food additives (E171) and have been associated with potential adverse effects on health. However, little knowledge is available regarding the interactions between TiO 2 nanoparticles (NPs) and other food components, such as flavonoids. In this study, we aim to study the molecular interactions between TiO 2 anatase NPs and three structurally closely related polymethoxyflavones (PMFs, flavonoids found in citrus fruits), namely, 3',4'-didemethylnobiletin (DDN), 5-demethylnobiletin (5DN), and 5,3',4'-tridemethylnobiletin (TDN), using ultraviolet-visible (UV-vis) spectrometry and surface-enhanced Raman spectroscopy (SERS). In the UV-vis absorption spectra, bathochromic effects were observed after DDN and TDN conjugated with TiO 2 NPs. The results from SERS analysis clearly demonstrated that DDN and TDN could bind TiO 2 NPs with the functional groups 3'-OH and 4'-OH on ring B and formed charge-transfer complexes. However, 5DN with functional groups C═O on ring C and 5-OH on ring A could not bind TiO 2 NPs. Knowledge on the molecular interactions between TiO 2 NPs and food components, such as flavonoids, will facilitate the understanding of the fate of TiO 2 NPs during food processing and in the gastrointestinal tract after oral consumption.

  2. Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks.

    PubMed

    Wang, Yingying; Chang, Jianhui; Shao, Lijian; Feng, Wei; Luo, Yi; Chow, Marie; Du, Wei; Meng, Aimin; Zhou, Daohong

    2016-06-01

    Down syndrome (DS) is a genetic disorder caused by the presence of an extra partial or whole copy of chromosome 21. In addition to musculoskeletal and neurodevelopmental abnormalities, children with DS exhibit various hematologic disorders and have an increased risk of developing acute lymphoblastic leukemia and acute megakaryocytic leukemia. Using the Ts65Dn mouse model, we investigated bone marrow defects caused by trisomy for 132 orthologs of the genes on human chromosome 21. The results showed that, although the total bone marrow cellularity as well as the frequency of hematopoietic progenitor cells (HPCs) was comparable between Ts65Dn mice and their age-matched euploid wild-type (WT) control littermates, human chromosome 21 trisomy led to a significant reduction in hematopoietic stem cell (HSC) numbers and clonogenic function in Ts65Dn mice. We also found that spontaneous DNA double-strand breaks (DSBs) were significantly increased in HSCs from the Ts65Dn mice, which was correlated with the significant reduction in HSC clonogenic activity compared to those from WT controls. Moreover, analysis of the repair kinetics of radiation-induced DSBs revealed that HSCs from Ts65Dn mice were less proficient in DSB repair than the cells from WT controls. This deficiency was associated with a higher sensitivity of Ts65Dn HSCs to radiation-induced suppression of HSC clonogenic activity than that of euploid HSCs. These findings suggest that an additional copy of genes on human chromosome 21 may selectively impair the ability of HSCs to repair DSBs, which may contribute to DS-associated hematological abnormalities and malignancies.

  3. Diabetic nephropathy research in China: Data analysis and review from the National Natural Science Foundation of China.

    PubMed

    Wan, Qiang; Xu, Yanying; Dong, Erdan

    2015-05-01

    As the largest funding agency of natural science of China, the National Natural Science Foundation of China (NSFC) has made great efforts in promoting the development of diabetic nephropathy (DN) research in recent years. The aim of the current study is to summarize the diabetic nephropathy research in China by analyzing NSFC-funded projects. Data on all projects in the DN field funded by NSFC from 1986 to 2013 were collected. The funding tendency, funding areas, and hotspots in the DN field, and major research institutions, were analyzed. As one output of this support, outstanding research groups in China, and their representative studies, are also highlighted. From 1986 to 2013, the NSFC has funded a total of 248 projects in the DN field, with a total funding amount of 91.5 million RMB (US$14.9 million). A rapid increase could be seen in the past 5 years, with an average annual 30% increase in projects numbers and a 52% increase in funding amount. All fields in DN research have been covered by the NSFC, including etiology, pathophysiology, diagnostics, and therapeutics. Along with increased funding of the DN research, there has been a growth in the papers published in Science Citation Index journals by Chinese scholars. In the past decade, the funding scale and funding budget have increased dramatically. Benefiting from this, DN research in China has also made considerable progression. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  4. The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis.

    PubMed

    Shao, Weijuan; Xiong, Xiaoquan; Ip, Wilfred; Xu, Fenghao; Song, Zhuolun; Zeng, Kejing; Hernandez, Marcela; Liang, Tao; Weng, Jianping; Gaisano, Herbert; Nostro, M Cristina; Jin, Tianru

    2015-04-01

    Disruption of TCF7L2 in mouse pancreatic β-cells has generated different outcomes in several investigations. Here we aim to clarify role of β-cell TCF7L2 and Wnt signaling using a functional-knockdown approach. Adenovirus-mediated dominant negative TCF7L2 (TCF7L2DN) expression was conducted in Ins-1 cells. The fusion gene in which TCF7L2DN expression is driven by P TRE3G was utilized to generate the transgenic mouse line TCF7L2DN Tet . The double transgenic line was created by mating TCF7L2DN Tet with Ins2-rtTA, designated as βTCFDN. β-cell specific TCF7L2DN expression was induced in βTCFDN by doxycycline feeding. TCF7L2DN expression in Ins-1 cells reduced GSIS, cell proliferation and expression of a battery of genes including incretin receptors and β-cell transcription factors. Inducing TCF7L2DN expression in βTCFDN during adulthood or immediately after weaning generated no or very modest metabolic defect, while its expression during embryonic development by doxycycline feeding in pregnant mothers resulted in significant glucose intolerance associated with altered β-cell gene expression and reduced β-cell mass. Our observations support a cell autonomous role for TCF7L2 in pancreatic β-cells suggested by most, though not all, investigations. βTCFDN is a novel model for further exploring the role of TCF7L2 in β-cell genesis and metabolic homeostasis.

  5. Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice.

    PubMed

    Yan, Jian; Ginsberg, Stephen D; Powers, Brian; Alldred, Melissa J; Saltzman, Arthur; Strupp, Barbara J; Caudill, Marie A

    2014-10-01

    Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a trisomic mouse model of Down syndrome and Alzheimer's disease. To gain insight into the mechanisms underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters choline metabolism in adult Ts65Dn offspring. Deuterium-labeled methyl-d9-choline was administered to adult Ts65Dn and disomic (2N) female littermates born to choline-unsupplemented or choline-supplemented Ts65Dn dams. Enrichment of d9-choline metabolites (derived from intact choline) and d3 + d6-choline metabolites [produced when choline-derived methyl groups are used by phosphatidylethanolamine N-methyltransferase (PEMT)] was measured in harvested tissues. Adult offspring (both Ts65Dn and 2N) of choline-supplemented (vs. choline-unsupplemented) dams exhibited 60% greater (P≤0.007) activity of hepatic PEMT, which functions in de novo choline synthesis and produces phosphatidylcholine (PC) enriched in docosahexaenoic acid. Higher (P<0.001) enrichment of PEMT-derived d3 and d6 metabolites was detected in liver, plasma, and brain in both genotypes but to a greater extent in the Ts65Dn adult offspring. MCS also yielded higher (P<0.05) d9 metabolite enrichments in liver, plasma, and brain. These data demonstrate that MCS exerts lasting effects on offspring choline metabolism, including up-regulation of the hepatic PEMT pathway and enhanced provision of choline and PEMT-PC to the brain. © FASEB.

  6. What if? Neural activity underlying semantic and episodic counterfactual thinking.

    PubMed

    Parikh, Natasha; Ruzic, Luka; Stewart, Gregory W; Spreng, R Nathan; De Brigard, Felipe

    2018-05-25

    Counterfactual thinking (CFT) is the process of mentally simulating alternative versions of known facts. In the past decade, cognitive neuroscientists have begun to uncover the neural underpinnings of CFT, particularly episodic CFT (eCFT), which activates regions in the default network (DN) also activated by episodic memory (eM) recall. However, the engagement of DN regions is different for distinct kinds of eCFT. More plausible counterfactuals and counterfactuals about oneself show stronger activity in DN regions compared to implausible and other- or object-focused counterfactuals. The current study sought to identify a source for this difference in DN activity. Specifically, self-focused counterfactuals may also be more plausible, suggesting that DN core regions are sensitive to the plausibility of a simulation. On the other hand, plausible and self-focused counterfactuals may involve more episodic information than implausible and other-focused counterfactuals, which would imply DN sensitivity to episodic information. In the current study, we compared episodic and semantic counterfactuals generated to be plausible or implausible against episodic and semantic memory reactivation using fMRI. Taking multivariate and univariate approaches, we found that the DN is engaged more during episodic simulations, including eM and all eCFT, than during semantic simulations. Semantic simulations engaged more inferior temporal and lateral occipital regions. The only region that showed strong plausibility effects was the hippocampus, which was significantly engaged for implausible CFT but not for plausible CFT, suggestive of binding more disparate information. Consequences of these findings for the cognitive neuroscience of mental simulation are discussed. Published by Elsevier Inc.

  7. AGED DOMINANT NEGATIVE p38α MAPK MICE ARE RESISTANT TO AGE-DEPENDENT DECLINE IN ADULT-NEUROGENESIS AND CONTEXT DISCRIMINATION FEAR CONDITIONING

    PubMed Central

    Cortez, IbDanelo; Bulavin, Dmitry V.; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

    2018-01-01

    A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38αAF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38αAF/+) and kinase activity. As a result, aged DN-p38αAF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer’s disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual’s relative risk. In the present study, we evaluated aged DN-p38αAF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38αAF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38αAF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38αAF/+, we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38αAF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. PMID:27765672

  8. A polymorphism in the gene encoding carnosinase (CNDP1) as a predictor of mortality and progression from nephropathy to end-stage renal disease in type 1 diabetes mellitus.

    PubMed

    Alkhalaf, A; Bakker, S J L; Bilo, H J G; Gans, R O B; Navis, G J; Postmus, D; Forsblom, C; Groop, P H; Vionnet, N; Hadjadj, S; Marre, M; Parving, H H; Rossing, P; Tarnow, L

    2010-12-01

    Homozygosity for a five leucine repeat (5L-5L) in the carnosinase gene (CNDP1) has been found to be cross-sectionally associated with a low frequency of diabetic nephropathy (DN), mainly in type 2 diabetes. We prospectively investigated in patients with type 1 diabetes whether: (1) 5L-5L is associated with mortality; (2) there is an interaction of 5L-5L with DN or sex for prediction of mortality; and (3) 5L-5L is associated with progression to end-stage renal disease (ESRD). In this prospective study in white European patients with type 1 diabetes, individuals with DN were defined by persistent albuminuria ≥ 300 mg/24 h. Controls without nephropathy were defined by persistent (>15 years) normoalbuminuria < 30 mg/24 h. Leucine repeats were assessed with a fluorescent DNA analysis system. Onset of ESRD was defined by need to start chronic dialysis or kidney transplantation. The study involved 916 patients with DN and 1,170 controls. During follow-up for 8.8 years, 107 patients (14%) with 5L-5L died compared with 182 patients (13.8%) with other genotypes (p = 0.99). There was no significant interaction of 5L-5L with DN for prediction of mortality (p = 0.57), but a trend towards interaction with sex (p = 0.08). In patients with DN, HR for ESRD in 5L-5L vs other genotypes was not constant over time, with increased risk for 5L-5L beyond 8 years of follow-up (p = 0.03). CNDP1 polymorphism was not associated with mortality, and nor was there an interaction of this polymorphism with DN for prediction of mortality in patients with type 1 diabetes. CNDP1 polymorphism predicts progression to ESRD in patients with DN, but only late after baseline measurements.

  9. Further evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) on chromosome Ip, and evidence for genetic heterogeneity

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

    Goldstein, A.M.; Fraser, M.C.; McBride, O.W.

    Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. The authors examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three linkage analyses were performed: (1) CMM alone - all individuals without confirmed melanoma or borderline lesions were considered unaffected (model I); (2) CMM/DN with variable age at onset and sporadics (model II); and (3) CMM/DN using the model of Bale et al. (model III). For CMM alone and D1S47, Z[sub max] = 3.12 atmore » [theta] = .10. For D1S160 and CMM alone, Z[sub max] = 1.76 at [theta] = .10. PND showed no evidence for linkage to CMM alone. Models II and III showed strong evidence for linkage to D1S47, D1S160, and PND in the set A pedigrees but not in the set B families. The authors tested for homogeneity of CMM/DN (model II) by splitting families into two groups on the basis of (1) the proportion of CMM/DN cases and (2) the occurrence of immune-related tumors. In group 1 there was significant evidence of heterogeneity with both D1S47 and D1S160, and in group 2 there was significant evidence of heterogeneity with D1S160. Thus, diagnostic, clinical, and genetic heterogeneity are the likely reasons that previous studies have failed to confirm linkage of CMM/DN to chromosome 1p. The results showed significant evidence for a CMM locus linked to D1S47, as well as significant evidence for heterogeneity with only a subset of the families appearing linked to chromosome 1p. 38 refs., 1 fig., 5 tabs.« less

  10. AMPKα2 deficiency uncovers time dependency in the regulation of contraction-induced palmitate and glucose uptake in mouse muscle.

    PubMed

    Abbott, Marcia J; Bogachus, Lindsey D; Turcotte, Lorraine P

    2011-07-01

    AMP-activated protein kinase (AMPK) is a fuel sensor in skeletal muscle with multiple downstream signaling targets that may be triggered by increases in intracellular Ca(2+) concentration ([Ca(2+)]). The purpose of this study was to determine whether increases in intracellular [Ca(2+)] induced by caffeine act solely via AMPKα(2) and whether AMPKα(2) is essential to increase glucose uptake, fatty acid (FA) uptake, and FA oxidation in contracting skeletal muscle. Hindlimbs from wild-type (WT) or AMPKα(2) dominant-negative (DN) transgene mice were perfused during rest (n = 11), treatment with 3 mM caffeine (n = 10), or muscle contraction (n = 11). Time-dependent effects on glucose and FA uptake were uncovered throughout the 20-min muscle contraction perfusion period (P < 0.05). Glucose uptake rates did not increase in DN mice during muscle contraction until the last 5 min of the protocol (P < 0.05). FA uptake rates were elevated at the onset of muscle contraction and diminished by the end of the protocol in DN mice (P < 0.05). FA oxidation rates were abolished in the DN mice during muscle contraction (P < 0.05). The DN transgene had no effect on caffeine-induced FA uptake and oxidation (P > 0.05). Glucose uptake rates were blunted in caffeine-treated DN mice (P < 0.05). The DN transgene resulted in a greater use of intramuscular triglycerides as a fuel source during muscle contraction. The DN transgene did not alter caffeine- or contraction-mediated changes in the phosphorylation of Ca(2+)/calmodulin-dependent protein kinase I or ERK1/2 (P > 0.05). These data suggest that AMPKα(2) is involved in the regulation of substrate uptake in a time-dependent manner in contracting muscle but is not necessary for regulation of FA uptake and oxidation during caffeine treatment.

  11. Rapeseed protein-derived antioxidant peptide RAP alleviates renal fibrosis through MAPK/NF-κB signaling pathways in diabetic nephropathy.

    PubMed

    Zhang, Mingyan; Yan, Zhibin; Bu, Lili; An, Chunmei; Wang, Dan; Liu, Xin; Zhang, Jianfeng; Yang, Wenle; Deng, Bochuan; Xie, Junqiu; Zhang, Bangzhi

    2018-01-01

    Kidney fibrosis is the main pathologic change in diabetic nephropathy (DN), which is the major cause of end-stage renal disease. Current therapeutic strategies slow down but cannot reverse the progression of renal dysfunction in DN. Plant-derived bioactive peptides in foodstuffs are widely used in many fields because of their potential pharmaceutical and nutraceutical benefits. However, this type of peptide has not yet been studied in renal fibrosis of DN. Previous studies have indicated that the peptide YWDHNNPQIR (named RAP), a natural peptide derived from rapeseed protein, has an antioxidative stress effect. The oxidative stress is believed to be associated with DN. The aim of this study was to evaluate the pharmacologic effects of RAP against renal fibrosis of DN and high glucose (HG)-induced mesangial dysfunction. Diabetes was induced by streptozotocin and high-fat diet in C57BL/6 mice and these mice were treated by subcutaneous injection of different doses of RAP (0.1 mg/kg and 0.5 mg/kg, every other day) or PBS for 12 weeks. Later, functional and histopathologic analyses were performed. Parallel experiments verifying the molecular mechanism by which RAP alleviates DN were carried out in HG-induced mesangial cells (MCs). RAP improved the renal function indices, including 24-h albuminuria, triglyceride, serum creatinine, and blood urea nitrogen levels, but did not lower blood glucose levels in DN mice. RAP also simultaneously attenuated extracellular matrix accumulation in DN mice and HG-induced MCs. Furthermore, RAP reduced HG-induced cell proliferation, but it showed no toxicity in MCs. Additionally, RAP inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. RAP can attenuate fibrosis in vivo and in vitro by antagonizing the MAPK and NF-κB pathways.

  12. Linking a dermal permeation and an inhalation model to a simple pharmacokinetic model to study airborne exposure to di(n-butyl) phthalate.

    PubMed

    Lorber, Matthew; Weschler, Charles J; Morrison, Glenn; Bekö, Gabriel; Gong, Mengyan; Koch, Holger M; Salthammer, Tunga; Schripp, Tobias; Toftum, Jørn; Clausen, Geo

    2017-11-01

    Six males clad only in shorts were exposed to high levels of airborne di(n-butyl) phthalate (DnBP) and diethyl phthalate (DEP) in chamber experiments conducted in 2014. In two 6 h sessions, the subjects were exposed only dermally while breathing clean air from a hood, and both dermally and via inhalation when exposed without a hood. Full urine samples were taken before, during, and for 48 h after leaving the chamber and measured for key DnBP and DEP metabolites. The data clearly demonstrated high levels of DnBP and DEP metabolite excretions while in the chamber and during the first 24 h once leaving the chamber under both conditions. The data for DnBP were used in a modeling exercise linking dose models for inhalation and transdermal permeation with a simple pharmacokinetic model that predicted timing and mass of metabolite excretions. These models were developed and calibrated independent of these experiments. Tests included modeling of the "hood-on" (transdermal penetration only), "hood-off" (both inhalation and transdermal) scenarios, and a derived "inhalation-only" scenario. Results showed that the linked model tended to duplicate the pattern of excretion with regard to timing of peaks, decline of concentrations over time, and the ratio of DnBP metabolites. However, the transdermal model tended to overpredict penetration of DnBP such that predictions of metabolite excretions were between 1.1 and 4.5 times higher than the cumulative excretion of DnBP metabolites over the 54 h of the simulation. A similar overprediction was not seen for the "inhalation-only" simulations. Possible explanations and model refinements for these overpredictions are discussed. In a demonstration of the linked model designed to characterize general population exposures to typical airborne indoor concentrations of DnBP in the United States, it was estimated that up to one-quarter of total exposures could be due to inhalation and dermal uptake.

  13. Comparison of del Nido and St Thomas Cardioplegia Solutions in Pediatric Patients: A Prospective Randomized Clinical Trial.

    PubMed

    Talwar, Sachin; Bhoje, Amolkumar; Sreenivas, Vishnubhatla; Makhija, Neeti; Aarav, Sudheer; Choudhary, Shiv Kumar; Airan, Balram

    2017-01-01

    We conducted a prospective randomized trial to compare del Nido (DN) cardioplegia with conventional cold blood cardioplegia (St Thomas [STH]) in pediatric patients. We randomized 100 pediatric patients aged ≤12 years undergoing elective repair of ventricular septal defects and tetralogy of Fallot to the DN and the STH groups. In the DN group, a 20 mL/kg single dose was administered. In the STH group, a 30 mL/kg dose was administered, followed by repeated doses at 25- to 30-minute intervals. The primary outcome was cardiac index that was measured 4 times intra- and postoperatively. Troponin-I, interleukin-6, and tissue necrosis factor-alpha were measured. Myocardial biopsy was obtained to assess electron-microscopic ultrastructural changes. Cardiac indices were significantly higher in the DN group than in the STH group 2 hours after termination of cardiopulmonary bypass (P = 0.0006), after 6 hours (P = 0.0006), and after 24 hours (P ≤ 0.0001). On repeated measure regression analysis, the cardiac index was on an average 0.50 L/min/m 2 higher in the DN group than in the STH group at any time point (P = 0.002). Duration of mechanical ventilation (P = 0.01), intensive care unit stay (P = 0.01), and hospital stay (P = 0.0007) was significantly lower in the DN group. Patients in the DN group exhibited lower troponin-I release 24 hours following cardiopulmonary bypass (P = 0.021). Electron microscopic studies showed more myofibrillar disarray in the STH group (P = 0.02). Use of long-acting DN cardioplegia solution was associated with better preservation of cardiac index, lesser troponin-I release, and decreased morbidity. Ultrastructural changes showed better preservation of myofibrillar architecture. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

    PubMed

    Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

    2011-06-01

    A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P < .0001). The mean relative values of type 2 collagen mRNAs in the regenerated tissue were obviously higher in the DN gel-implanted defect than in the untreated control at each period. The mean surface roughness of the untreated control was significantly higher than the normal cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

  15. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways

    PubMed Central

    Cappi, C; Brentani, H; Lima, L; Sanders, S J; Zai, G; Diniz, B J; Reis, V N S; Hounie, A G; Conceição do Rosário, M; Mariani, D; Requena, G L; Puga, R; Souza-Duran, F L; Shavitt, R G; Pauls, D L; Miguel, E C; Fernandez, T V

    2016-01-01

    Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein–protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10−8 per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions. PMID:27023170

  16. Inhibition of glycogen synthase kinase 3beta during heart failure is protective.

    PubMed

    Hirotani, Shinichi; Zhai, Peiyong; Tomita, Hideharu; Galeotti, Jonathan; Marquez, Juan Pablo; Gao, Shumin; Hong, Chull; Yatani, Atsuko; Avila, Jesús; Sadoshima, Junichi

    2007-11-26

    Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3beta during heart failure could be compensatory.

  17. Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning.

    PubMed

    Cortez, IbDanelo; Bulavin, Dmitry V; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

    2017-03-30

    A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α AF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α AF/+ ) and kinase activity. As a result, aged DN-p38α AF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer's disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual's relative risk. In the present study, we evaluated aged DN-p38α AF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38α AF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38α AF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38α AF/+ , we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38α AF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Maternal choline supplementation in a mouse model of Down syndrome: effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring

    PubMed Central

    Powers, Brian E.; Kelley, Christy M.; Velazquez, Ramon; Ash, Jessica A.; Strawderman, Myla S.; Alldred, Melissa J.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

    2016-01-01

    The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer’s disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12–17 months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD. PMID:27840230

  19. Maternal choline supplementation in a mouse model of Down syndrome: Effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring.

    PubMed

    Powers, Brian E; Kelley, Christy M; Velazquez, Ramon; Ash, Jessica A; Strawderman, Myla S; Alldred, Melissa J; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

    2017-01-06

    The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer's disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12-17months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Hyaluronic acid enhances the effect of the PAMPS/PDMAAm double-network hydrogel on chondrogenic differentiation of ATDC5 cells

    PubMed Central

    2014-01-01

    Background A double-network (DN) gel, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N,N’-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated whether DN gel induced chondrogenic differentiation of ATDC5 cells in a maintenance medium without insulin, and whether supplementation of hyaluronic acid enhanced the chondrogenic differentiation effect of DN gel. Methods ATDC5 cells were cultured on the DN gel and the polystyrene (PS) dish in maintenance media without insulin for 21 days. Hyaluronic acid having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.01, 0.1, or 1.0 mg/mL. The cultured cells were evaluated using immunocytochemistry for type-2 collagen and real time PCR for gene expression of type-2 collagen, aggrecan, and Sox9 at 7 and 21 days of culture. Results The cells cultured on the DN gel formed nodules and were stained with an anti-type-2 collagen antibody, and expression of type-2 collagen and aggrecan mRNA was significantly greater on the DN gel than on the PS dish surface (p < 0.05) in the hyaluronic acid-free maintenance medium. Hyaluronic acid supplementation of a high concentration (1.0 mg/mL) significantly enhanced expression of type-2 collagen and aggrecan mRNA in comparison with culture without hyaluronic acid at 21 days (p < 0.05). Conclusions The DN gel induced chondrogenic differentiation of ATDC5 cells without insulin. This effect was significantly affected by hyaluronic acid, depending on the level of concentration. There is a high possibility that hyaluronic acid plays an important role in the in vivo hyaline cartilage regeneration phenomenon induced by the DN gel. PMID:24997593

  1. Hyaluronic acid enhances the effect of the PAMPS/PDMAAm double-network hydrogel on chondrogenic differentiation of ATDC5 cells.

    PubMed

    Kitamura, Nobuto; Kurokawa, Takayuki; Fukui, Takaaki; Gong, Jian P; Yasuda, Kazunori

    2014-07-06

    A double-network (DN) gel, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated whether DN gel induced chondrogenic differentiation of ATDC5 cells in a maintenance medium without insulin, and whether supplementation of hyaluronic acid enhanced the chondrogenic differentiation effect of DN gel. ATDC5 cells were cultured on the DN gel and the polystyrene (PS) dish in maintenance media without insulin for 21 days. Hyaluronic acid having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.01, 0.1, or 1.0 mg/mL. The cultured cells were evaluated using immunocytochemistry for type-2 collagen and real time PCR for gene expression of type-2 collagen, aggrecan, and Sox9 at 7 and 21 days of culture. The cells cultured on the DN gel formed nodules and were stained with an anti-type-2 collagen antibody, and expression of type-2 collagen and aggrecan mRNA was significantly greater on the DN gel than on the PS dish surface (p < 0.05) in the hyaluronic acid-free maintenance medium. Hyaluronic acid supplementation of a high concentration (1.0 mg/mL) significantly enhanced expression of type-2 collagen and aggrecan mRNA in comparison with culture without hyaluronic acid at 21 days (p < 0.05). The DN gel induced chondrogenic differentiation of ATDC5 cells without insulin. This effect was significantly affected by hyaluronic acid, depending on the level of concentration. There is a high possibility that hyaluronic acid plays an important role in the in vivo hyaline cartilage regeneration phenomenon induced by the DN gel.

  2. The Arabidopsis Rho of Plants GTPase AtROP6 Functions in Developmental and Pathogen Response Pathways1[C][W][OA

    PubMed Central

    Poraty-Gavra, Limor; Zimmermann, Philip; Haigis, Sabine; Bednarek, Paweł; Hazak, Ora; Stelmakh, Oksana Rogovoy; Sadot, Einat; Schulze-Lefert, Paul; Gruissem, Wilhelm; Yalovsky, Shaul

    2013-01-01

    How plants coordinate developmental processes and environmental stress responses is a pressing question. Here, we show that Arabidopsis (Arabidopsis thaliana) Rho of Plants6 (AtROP6) integrates developmental and pathogen response signaling. AtROP6 expression is induced by auxin and detected in the root meristem, lateral root initials, and leaf hydathodes. Plants expressing a dominant negative AtROP6 (rop6DN) under the regulation of its endogenous promoter are small and have multiple inflorescence stems, twisted leaves, deformed leaf epidermis pavement cells, and differentially organized cytoskeleton. Microarray analyses of rop6DN plants revealed that major changes in gene expression are associated with constitutive salicylic acid (SA)-mediated defense responses. In agreement, their free and total SA levels resembled those of wild-type plants inoculated with a virulent powdery mildew pathogen. The constitutive SA-associated response in rop6DN was suppressed in mutant backgrounds defective in SA signaling (nonexpresser of PR genes1 [npr1]) or biosynthesis (salicylic acid induction deficient2 [sid2]). However, the rop6DN npr1 and rop6DN sid2 double mutants retained the aberrant developmental phenotypes, indicating that the constitutive SA response can be uncoupled from ROP function(s) in development. rop6DN plants exhibited enhanced preinvasive defense responses to a host-adapted virulent powdery mildew fungus but were impaired in preinvasive defenses upon inoculation with a nonadapted powdery mildew. The host-adapted powdery mildew had a reduced reproductive fitness on rop6DN plants, which was retained in mutant backgrounds defective in SA biosynthesis or signaling. Our findings indicate that both the morphological aberrations and altered sensitivity to powdery mildews of rop6DN plants result from perturbations that are independent from the SA-associated response. These perturbations uncouple SA-dependent defense signaling from disease resistance execution. PMID:23319551

  3. Presentation, pathology and prognosis of renal disease in type 2 diabetes

    PubMed Central

    Tan, Jasmine; Zwi, L Jonathan; Collins, John F; Marshall, Mark R; Cundy, Tim

    2017-01-01

    Objective Non-diabetic renal disease (NDRD) is common in patients with type 2 diabetes (T2D), but the relationship between its presentation and prognosis is unknown. Research design and methods In a retrospective cohort study, we compared renal and patient survival among 263 patients with T2D who had native renal biopsies between 2002 and 2008 from three Auckland hospitals in New Zealand. The presence of diabetic nephropathy (DN), NDRD or mixed (DN and NDRD) was determined from biopsy. We examined clinical associations according to NDRD etiologies and mode of presentation—acute (defined by acute kidney injury (AKI)) or non-acute. Patients were followed until end-stage renal disease, death or December 2015. Survival was compared using Log-rank test. Results 94 (36%) patients had DN, 72 (27%) had NDRD, and 97 (37%) had mixed pathologies. Obesity-related focal segmental glomerulosclerosis was the most common NDRD (46%) in patients with non-acute presentations, whereas interstitial nephritis or immune-complex glomerulonephritides were the most prevalent in those with acute presentations (60%). DN was commonly associated with AKI (p<0.001). The prevalence of DN increased with diabetes duration (p<0.001), but NDRD was still found in 55% of subjects with ≥14 years T2D. NDRD was strongly associated with the absence of retinopathy (p<0.001). Renal survival was best in the NDRD group (p<0.001). Among those with DN, renal prognosis was worse in those with more advanced DN lesions and those with an acute presentation (p<0.001). The proportion of all-cause mortality was similar in all three groups, but overall survival was poorest in the DN group (p=0.025). Conclusions Renal disease in patients with T2D is heterogeneous. The renal prognosis differs markedly according to histopathological diagnosis and mode of presentation. PMID:28878938

  4. Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes

    PubMed Central

    Keck-Wherley, Jennifer; Grover, Deepak; Bhattacharyya, Sharmistha; Xu, Xiufen; Holman, Derek; Lombardini, Eric D.; Verma, Ranjana; Biswas, Roopa; Galdzicki, Zygmunt

    2011-01-01

    Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21. Elevated levels of several microRNAs (miRNAs) located on chromosome 21 have been reported in human DS heart and brain tissues. The Ts65Dn mouse model is the most investigated DS model with a triplicated segment of mouse chromosome 16 harboring genes orthologous to those on human chromosome 21. Using ABI TaqMan miRNA arrays, we found a set of miRNAs that were significantly up- or downregulated in the Ts65Dn hippocampus compared to euploid controls. Furthermore, miR-155 and miR-802 showed significant overexpression in the Ts65Dn hippocampus, thereby confirming results of previous studies. Interestingly, miR-155 and miR-802 were also overexpressed in the Ts65Dn whole blood but not in lung tissue. We also found overexpression of the miR-155 precursors, pri- and pre-miR-155 derived from the miR-155 host gene, known as B cell integration cluster, suggesting enhanced biogenesis of miR-155. Bioinformatic analysis revealed that neurodevelopment, differentiation of neuroglia, apoptosis, cell cycle, and signaling pathways including ERK/MAPK, protein kinase C, phosphatidylinositol 3-kinase, m-TOR and calcium signaling are likely targets of these miRNAs. We selected some of these potential gene targets and found downregulation of mRNA encoding Ship1, Mecp2 and Ezh2 in Ts65Dn hippocampus. Interestingly, the miR-155 target gene Ship1 (inositol phosphatase) was also downregulated in Ts65Dn whole blood but not in lung tissue. Our findings provide insights into miRNA-mediated gene regulation in Ts65Dn mice and their potential contribution to impaired hippocampal synaptic plasticity and neurogenesis, as well as hemopoietic abnormalities observed in DS. PMID:22042248

  5. 76 FR 41822 - In the Matter of Certain Toner Cartridges and Components Thereof; Notice of Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    ...Notice is hereby given that the presiding administrative law judge (``ALJ'') has issued a Final Initial Determination on Violation of Section 337 and Recommended Determination on Remedy and Bonding in the above-captioned investigation. The Commission is soliciting comments on public interest issues raised by the recommended relief should the Commission find a violation of section 337. The ALJ recommended, should the Commission find a violation, that the Commission issue a limited exclusion order directed against certain memory modules and components thereof, and products containing same imported by respondents SK Hynix Inc. of Gyeoonggi-do, Republic of Korea; and SK Hynix America, Inc. and SK Hynix Memory Solutions Inc., both of San Jose, California. This notice is soliciting public interest comments from the public only. Parties are to file public interest submissions pursuant to Commission rules.

  10. Carbonate fuel cell and components thereof for in-situ delayed addition of carbonate electrolyte

    DOEpatents

    Johnsen, Richard [Waterbury, CT; Yuh, Chao-Yi [New Milford, CT; Farooque, Mohammad [Danbury, CT

    2011-05-10

    An apparatus and method in which a delayed carbonate electrolyte is stored in the storage areas of a non-electrolyte matrix fuel cell component and is of a preselected content so as to obtain a delayed time release of the electrolyte in the storage areas in the operating temperature range of the fuel cell.

  11. The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy.

    PubMed

    Yu, Ruichao; Bo, Hong; Villani, Vincenzo; Spencer, Philip J; Fu, Ping

    2016-01-01

    There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN). The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4) is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17) pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR) inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. Streptozotocin (STZ)-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6); and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6) and a control group (Control, n =6). Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through activation of Th17 cells. Rapamycin may attenuate DN via reduction of the TLR4 signaling pathway and Th17 cells signaling. Although the underlying mechanisms need to be explored, the observed increase of TLR4 and IL-17 during the early stages of DN and their suppression with rapamycin treatment suggest the importance of TLR4 and IL-17 in DN pathophysiology. © 2016 The Author(s) Published by S. Karger AG, Basel.

  12. Depletion of pro-inflammatory CD161(+) double negative (CD3(+)CD4(-)CD8(-)) T cells in AIDS patients is ameliorated by expansion of the γδ T cell population.

    PubMed

    Singleterry, Will L; Henderson, Harold; Cruse, Julius M

    2012-02-01

    In this present investigation, flow cytometry was utilized to evaluate 13 healthy controls and 31 HIV-1 infected patients who had advanced to the AIDS stage of infection (CD4 count below 200 cells/mm(3)), for the expression of CD161 on CD3(+) double negative (DN) (CD3(+)CD4(-)CD8(-)) T cells, CD4(+) T cells, CD8(+) T cells and γδ T cells. The observed depletion of CD161(+) T cells from peripheral circulation was due primarily to the loss of CD4(+)CD161(+) T cells; as these cells represented 8.67±0.74% of the total healthy control peripheral T cell population, while the CD4(+)CD161(+) T cells of the AIDS group represented only 3.35±0.41% (p=<0.0001) of the total peripheral T cell population. We have also shown here that the DN T cell population was more than doubled in the AIDS group, with the DN T cell population expanding from 3.29±0.45% of the healthy control peripheral T cell population to 8.64±1.16% (p=0.0001) of the AIDS group peripheral T cell population. By evaluating the expression of CD161 on the surface of the DN T cells we showed that within the healthy control group, 47.4±4.99% of the DN T cells were positive for the expression of CD161, while only 26.4±3.54% (p=0.002) of the AIDS group's DN T cells expressed CD161. Despite CD161 expression being halved on the DN T cells of the AIDS group, when we compared the total peripheral T cell percentage of CD161(+) DN T cells between the healthy control group and the AIDS group, there was no statistical difference. Even though only 26.4% DN T cells within the AIDS group were positive for CD161(+), the overall DN T cell population had expanded to such an extent that there was no statistical difference between the groups with regard to CD161(+) DN T cells as a percentage of the total peripheral T cell population. Furthermore, we showed that within the DN T cell population, there was an approximate 2:1 ratio of γδ to αβ T cells, and this ratio was maintained in both the healthy control group and the AIDS group. While evaluating γδ T cells we also discovered that CD8(+) γδ T cells were expanded from 0.62±.09% of the healthy control peripheral T cell population to 5.01±.88% (p=<0.0001) of the peripheral T cell population of the AIDS group; and that this population of CD8(+) γδ T cells underwent the same reduction in percentage of cells expressing CD161(+), further demonstrated that the phenomenon of CD161(+) percentage reduction and compensatory increase in total cell population was affecting the entire circulating γδ T cell population. Copyright © 2011 Elsevier Inc. All rights reserved.

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  19. Neural Responses to Heartbeats in the Default Network Encode the Self in Spontaneous Thoughts.

    PubMed

    Babo-Rebelo, Mariana; Richter, Craig G; Tallon-Baudry, Catherine

    2016-07-27

    The default network (DN) has been consistently associated with self-related cognition, but also to bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the first-person perspective subject or agent in the thought ("I"), and on another scale to what degree they were thinking about themselves ("Me"). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the "I" and the "Me" dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN. The default network (DN) has been consistently associated with self-processing but also with autonomic regulation. We hypothesized that these two functions could be functionally coupled in the DN, inspired by theories according to which selfhood is grounded in the neural monitoring of internal organs. Using magnetoencephalography, we show that heartbeat-evoked responses (HERs) in the DN covary with the self-relatedness of ongoing spontaneous thoughts. HER amplitude in the ventral precuneus covaried with the "I" self-dimension, whereas HER amplitude in the ventromedial prefrontal cortex encoded the "Me" self-dimension. Our experimental results directly support theories rooting selfhood in the neural monitoring of internal organs. We propose a novel functional framework for the DN, where self-processing is coupled with physiological monitoring. Copyright © 2016 Babo-Rebelo et al.

  20. Neural Responses to Heartbeats in the Default Network Encode the Self in Spontaneous Thoughts

    PubMed Central

    Babo-Rebelo, Mariana; Richter, Craig G.

    2016-01-01

    The default network (DN) has been consistently associated with self-related cognition, but also to bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the first-person perspective subject or agent in the thought (“I”), and on another scale to what degree they were thinking about themselves (“Me”). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the “I” and the “Me” dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN. SIGNIFICANCE STATEMENT The default network (DN) has been consistently associated with self-processing but also with autonomic regulation. We hypothesized that these two functions could be functionally coupled in the DN, inspired by theories according to which selfhood is grounded in the neural monitoring of internal organs. Using magnetoencephalography, we show that heartbeat-evoked responses (HERs) in the DN covary with the self-relatedness of ongoing spontaneous thoughts. HER amplitude in the ventral precuneus covaried with the “I” self-dimension, whereas HER amplitude in the ventromedial prefrontal cortex encoded the “Me” self-dimension. Our experimental results directly support theories rooting selfhood in the neural monitoring of internal organs. We propose a novel functional framework for the DN, where self-processing is coupled with physiological monitoring. PMID:27466329

  1. EFFECTS OF LONG-TERM MEMANTINE ON MEMORY AND NEUROPATHOLOGY IN TS65DN MICE, A MODEL FOR DOWN SYNDROME

    PubMed Central

    Lockrow, Jason; Boger, Heather; Bimonte-Nelson, Heather; Granholm, Ann-Charlotte

    2010-01-01

    Memantine is a partial NMDA receptor antagonist that has been shown to improve learning and memory in several animal models, and is approved for the treatment of Alzheimer’s disease. Chronic treatments using memantine in animal models of Alzheimer’s disease show disease-modifying effects and suggest a potential neuroprotective function. The present study assessed the effects of both short- and long-term memantine treatment in a mouse model of Down syndrome, the Ts65Dn mouse. The Ts65Dn mouse contains a partial trisomy of murine chromosome 16, and exhibits hippocampal-dependent memory deficits, as well as progressive degeneration of basal forebrain cholinergic neurons. Ts65Dn mice were treated with memantine for a period of six months, beginning at four months of age. At the end of treatment the mice underwent memory testing using novel object recognition and water radial arm maze tasks, and then histologically analyzed for markers of neurodegeneration. Memantine treatment improved spatial and recognition memory performance in the Ts65Dn mice, though not to the level of normosomic littermate controls. Despite these memory improvements, histological analysis found no morphological signs of neuroprotection of basal forebrain cholinergic or locus coeruleus neurons in memantine-treated Ts65Dn mice. However, memantine treatment of Ts65Dn mice gave rise to elevated brain-derived neurotrophic factor expression in the hippocampus and frontal cortex, suggesting a mechanism of behavioral modification. Thus, our findings provide further evidence for memory facilitation of memantine, but suggest pharmacological rather than neuroprotective effects of memantine both after acute and chronic treatment in this mouse model. PMID:20363261

  2. DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila.

    PubMed

    Zhang, Luoying; Chung, Brian Y; Lear, Bridget C; Kilman, Valerie L; Liu, Yixiao; Mahesh, Guruswamy; Meissner, Rose-Anne; Hardin, Paul E; Allada, Ravi

    2010-04-13

    Daily behaviors in animals are determined by the interplay between internal timing signals from circadian clocks and environmental stimuli such as light. How these signals are integrated to produce timely and adaptive behavior is unclear. The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions. Flies also respond to the onset of light and dark with acute increases in activity. Mutants of a novel ion channel, narrow abdomen (na), lack a robust increase in activity in response to light and show reduced anticipatory behavior and free-running rhythms, providing a genetic link between photic responses and circadian clock function. We used tissue-specific rescue of na to demonstrate a role for approximately 16-20 circadian pacemaker neurons, a subset of the posterior dorsal neurons 1 (DN1(p)s), in mediating the acute response to the onset of light as well as morning anticipatory behavior. Circadian pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) are especially important for morning anticipation and free-running rhythms and send projections to the DN1(p)s. We also demonstrate that DN1(p)Pdfr expression is sufficient to rescue, at least partially, Pdfr morning anticipation defects as well as defects in free-running rhythms, including those in DN1 molecular clocks. Additionally, these DN1 clocks in wild-type flies are more strongly reset to timing changes in PDF clocks than other pacemaker neurons, suggesting that they are direct targets. Taking these results together, we demonstrate that the DN1(p)s lie at the nexus of PDF and photic signaling to produce appropriate daily behavior.

  3. On the onset of secondary flow and unsteady solutions through a loosely coiled rectangular duct for large aspect ratio

    NASA Astrophysics Data System (ADS)

    Shaha, Poly Rani; Rudro, Sajal Kanti; Poddar, Nayan Kumar; Mondal, Rabindra Nath

    2016-07-01

    The study of flows through coiled ducts and channels has attracted considerable attention not only because of their ample applications in Chemical, Mechanical, Civil, Nuclear and Biomechanical engineering but also because of their ample applications in other areas, such as blood flow in the veins and arteries of human and other animals. In this paper, a numerical study is presented for the fully developed two-dimensional flow of viscous incompressible fluid through a loosely coiled rectangular duct of large aspect ratio. Numerical calculations are carried out by using a spectral method, and covering a wide range of the Dean number, Dn, for two types of curvatures of the duct. The main concern of the present study is to find out effects of curvature as well as formation of secondary vortices on unsteady solutions whether the unsteady flow is steady-state, periodic, multi-periodic or chaotic, if Dn is increased. Time evolution calculations as well as their phase spaces are performed with a view to study the non-linear behavior of the unsteady solutions, and it is found that the steady-state flow turns into chaotic flow through various flow instabilities, if Dn is increased no matter what the curvature is. It is found that the unsteady flow is a steady-state solution for small Dn's and oscillates periodically or non-periodically (chaotic) between two- and twelve-vortex solutions, if Dn is increased. It is also found that the chaotic solution is weak for small Dn's but strong as Dn becomes large. Axial flow distribution is also investigated and shown in contour plots.

  4. Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

    PubMed

    Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

    2014-04-01

    Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

  5. Genotoxicity induced by monomethylarsonous acid (MMA+3) in mouse thymic developing T cells.

    PubMed

    Xu, Huan; Medina, Sebastian; Lauer, Fredine T; Douillet, Christelle; Liu, Ke Jian; Stýblo, Miroslav; Burchiel, Scott W

    2017-09-05

    Drinking water exposure to arsenic is known to cause immunotoxicity. Our previous studies demonstrated that monomethylarsonous acid (MMA +3 ) was the major arsenical species presented in mouse thymus cells after a 30 d drinking water exposure to arsenite (As +3 ). MMA +3 was also showed to be ten times more toxic than As +3 on the suppression of IL-7/STAT5 signaling in the double negative (DN) thymic T cells. In order to examine the genotoxicity induced by low to moderate doses of MMA +3 , isolated mouse thymus cells were treated with 5, 50 and 500nMMMA +3 for 18h in vitro. MMA +3 suppressed the proliferation of thymus cells in a dose dependent manner. MMA +3 at 5nM induced DNA damage in DN not double positive (DP) cells. Differential sensitivity to double strand breaks and reactive oxygen species generation was noticed between DN and DP cells at 50nM, but the effects were not seen at the high dose (500nM). A stronger apoptotic effect induced by MMA +3 was noticed in DN cells than DP cells at low doses (5 and 50nM), which was negated by the strong apoptosis induction at the high dose (500nM). Analysis of intracellular MMA +3 concentrations in DN and DP cells, revealed that more MMA +3 accumulated in the DN cells after the in vitro treatment. Collectively, these results suggested that MMA +3 could directly induce strong genotoxicity in the early developing T cells in the thymus. The DN cells were much more sensitive to MMA +3 induced genotoxicity and apoptosis than DP cells, probably due to the higher intracellular levels of MMA +3 . Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Increased Sparsity of Hippocampal CA1 Neuronal Ensembles in a Mouse Model of Down Syndrome Assayed by Arc Expression

    PubMed Central

    Smith-Hicks, Constance L.; Cai, Peiling; Savonenko, Alena V.; Reeves, Roger H.; Worley, Paul F.

    2017-01-01

    Down syndrome (DS) is the leading chromosomal cause of intellectual disability, yet the neural substrates of learning and memory deficits remain poorly understood. Here, we interrogate neural networks linked to learning and memory in a well-characterized model of DS, the Ts65Dn mouse. We report that Ts65Dn mice exhibit exploratory behavior that is not different from littermate wild-type (WT) controls yet behavioral activation of Arc mRNA transcription in pyramidal neurons of the CA1 region of the hippocampus is altered in Ts65Dn mice. In WT mice, a 5 min period of exploration of a novel environment resulted in Arc mRNA transcription in 39% of CA1 neurons. By contrast, the same period of exploration resulted in only ~20% of CA1 neurons transcribing Arc mRNA in Ts65Dn mice indicating increased sparsity of the behaviorally induced ensemble. Like WT mice the CA1 pyramidal neurons of Ts65Dn mice reactivated Arc transcription during a second exposure to the same environment 20 min after the first experience, but the size of the reactivated ensemble was only ~60% of that in WT mice. After repeated daily exposures there was a further decline in the size of the reactivated ensemble in Ts65Dn and a disruption of reactivation. Together these data demonstrate reduction in the size of the behaviorally induced network that expresses Arc in Ts65Dn mice and disruption of the long-term stability of the ensemble. We propose that these deficits in network formation and stability contribute to cognitive symptoms in DS. PMID:28217086

  7. Mangiferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli.

    PubMed

    Wang, Xiaodan; Gao, Lihui; Lin, Hua; Song, Jingling; Wang, Jinwen; Yin, Yumin; Zhao, Jianghu; Xu, Xiangwei; Li, Zhenkun; Li, Ling

    2018-04-05

    Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN. In the present study, we investigated the effects of mangiferin on nephropathy in streptozotocin (STZ)-induced diabetic rats; we focused on pathological factors related to autophagy in podocytes and the AMPK-mTOR-ULK1 pathway. The results showed that chronic treatment with mangiferin significantly decreased albuminuria, inhibited glomerular extracellular matrix expansion and restored the expression of nephrin, a podocyte marker, in diabetic rats; these results suggest that mangiferin delayed the process of DN and protected the podocytes. In addition, mangiferin induced autophagy, as shown by the up-regulation of LC3 II and the down-regulation of p62 in both DN rats and podocytes. Transmission electron microscope analyses showed that mangiferin increased the number of autophagosomes in the podocytes of DN rats. This underlying mechanism was associated with the up-regulation of AMPK phosphorylation, the down-regulation of mTOR phosphorylation and the up-regulation of p-ULK1. Taken together, mangiferin delayed the progression of DN and protected the podocytes by enhancing autophagy under diabetic conditions via the AMPK-mTOR-ULK1 pathway. These findings provide new insights into the molecular mechanisms underlying the renoprotective effects of mangiferin in DN. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks

    PubMed Central

    Wang, Yingying; Chang, Jianhui; Shao, Lijian; Feng, Wei; Luo, Yi; Chow, Marie; Du, Wei; Meng, Aimin; Zhou, Daohong

    2016-01-01

    Down syndrome (DS) is a genetic disorder caused by the presence of an extra partial or whole copy of chromosome 21. In addition to musculoskeletal and neurodevelopmental abnormalities, children with DS exhibit various hematologic disorders and have an increased risk of developing acute lymphoblastic leukemia and acute megakaryocytic leukemia. Using the Ts65Dn mouse model, we investigated bone marrow defects caused by trisomy for 132 orthologs of the genes on human chromosome 21. The results showed that, although the total bone marrow cellularity as well as the frequency of hematopoietic progenitor cells (HPCs) was comparable between Ts65Dn mice and their age-matched euploid wild-type (WT) control littermates, human chromosome 21 trisomy led to a significant reduction in hematopoietic stem cell (HSC) numbers and clonogenic function in Ts65Dn mice. We also found that spontaneous DNA double-strand breaks (DSBs) were significantly increased in HSCs from the Ts65Dn mice, which was correlated with the significant reduction in HSC clonogenic activity compared to those from WT controls. Moreover, analysis of the repair kinetics of radiation-induced DSBs revealed that HSCs from Ts65Dn mice were less proficient in DSB repair than the cells from WT controls. This deficiency was associated with a higher sensitivity of Ts65Dn HSCs to radiation-induced suppression of HSC clonogenic activity than that of euploid HSCs. These findings suggest that an additional copy of genes on human chromosome 21 may selectively impair the ability of HSCs to repair DSBs, which may contribute to DS-associated hematological abnormalities and malignancies. PMID:27243896

  9. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

    PubMed Central

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

    2015-01-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

  10. Sustainable Triblock Copolymers for Application as Thermoplastic Elastomers

    NASA Astrophysics Data System (ADS)

    Ding, Wenyue; Wang, Shu; Ganewatta, Mitra; Tang, Chuanbing; Robertson, Megan

    Thermoplastic elastomers (TPEs), combining the processing advantages of thermoplastics with the flexibility and extensibility of elastomeric materials, have found versatile applications in industry, including electronics, clothing, adhesives, and automotive components. ABA triblock copolymers, in which A represents glassy endblocks and B the rubbery midblock, are commercially available as TPEs, such as poly(styrene-b-butadiene-b-styrene) (SBS) or poly(styrene-b-isoprene-b-styrene) (SIS). However, the commercial TPEs are derived from fossil fuels. The finite availability of fossil fuels and the environmental impact of the petroleum manufacturing have led to the increased interest in the development of alternative polymeric materials from sustainable sources. Rosin acids are promising replacement for the petroleum source due to their abundance in conifers, rigid molecular structures, and ease of functionalization. In this study, we explored the utilization of a rosin acid derivative, poly(dehydroabietic ethyl methacrylate) (PDAEMA), as a sustainable alternative for the glassy domain. The triblock copolymer poly(dehydroabietic ethyl methacrylate-b-n-butyl acylate-b-dehydroabietic ethyl methacrylate) (DnBD) was synthesized and characterized. DnBD exhibited tunable morphological and thermal properties. Tensile testing revealed elastomeric behavior.

  11. Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson’s disease

    PubMed Central

    He, Naying; Huang, Pei; Ling, Huawei; Langley, Jason; Liu, Chunlei; Ding, Bei; Huang, Juan; Xu, Hongmin; Zhang, Yong; Zhang, Zhongping; Hu, Xiaoping; Chen, Shengdi; Yan, Fuhua

    2016-01-01

    Parkinson disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic-rigid dominant (AR)] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0 T MR system. Inter-group susceptibility differences in bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast to the AR group, the TD group was found to have increased susceptibility in the bilateral DN, when compared to healthy controls. In addition, susceptibility was positively correlated with tremor score in drug naive PD patients. These findings indicate that iron load within DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR phenotypes of PD can be differentiated on the basis of the susceptibility of the DN at least on the group level. PMID:27192177

  12. Effects of cell penetrating Notch inhibitory peptide conjugated to elastin-like polypeptide on glioblastoma cells.

    PubMed

    Opačak-Bernardi, Teuta; Ryu, Jung Su; Raucher, Drazen

    2017-07-01

    Notch pathway was found to be activated in most glioblastomas (GBMs), underlining the importance of Notch in formation and recurrence of GBM. In this study, a Notch inhibitory peptide, dominant negative MAML (dnMAML), was conjugated to elastin-like polypeptide (ELP) for tumor targeted delivery. ELP is a thermally responsive polypeptide that can be actively and passively targeted to the tumor site by localized application of hyperthermia. This complex was further modified with the addition of a cell penetrating peptide, SynB1, for improved cellular uptake and blood-brain barrier penetration. The SynB1-ELP1-dnMAML was examined for its cellular uptake, cytotoxicity, apoptosis, cell cycle inhibition and the inhibition of target genes' expression. SynB1-ELP1-dnMAML inhibited the growth of D54 and U251 cells by inducing apoptosis and cell cycle arrest, especially in the presence of hyperthermia. Hyperthermia increased overall uptake of the polypeptide by the cells and enhanced the resulting pharmacological effects of dnMAML, showing the inhibition of targets of Notch pathway such as Hes-1 and Hey-L. These results confirm that dnMAML is an effective Notch inhibitor and combination with ELP may allow thermal targeting of the SynB1-ELP1-dnMAML complex in cancer cells while avoiding the dangers of systemic Notch inhibition.

  13. A DWARF NOVA IN THE GLOBULAR CLUSTER M13

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

    Servillat, M.; Van den Berg, M.; Grindlay, J.

    Dwarf novae (DNe) in globular clusters (GCs) seem to be rare with only 13 detections in the 157 known Galactic GCs. We report the identification of a new DN in M13, the 14th DN identified in a GC to date. Using the 2 m Faulkes Telescope North, we conducted a search for stars in M13 that show variability over a year (2005-2006) on timescales of days and months. This led to the detection of one DN showing several outbursts. A Chandra X-ray source is coincident with this DN and shows both a spectrum and variability consistent with that expected frommore » a DN, thus supporting the identification. We searched for a counterpart in Hubble Space Telescope Advanced Camera for Surveys/Wide Field Camera archived images and found at least 11 candidates, of which we could characterize only the 7 brightest, including one with a 3{sigma} H{alpha} excess and a faint blue star. The detection of one DN when more could have been expected likely indicates that our knowledge of the global Galactic population of cataclysmic variables is too limited. The proportion of DNe may be lower than found in catalogs, or they may have a much smaller mean duty cycle ({approx}1%) as proposed by some population synthesis models and recent observations in the field.« less

  14. Application of the ReNuMa model in the Sha He river watershed: tools for watershed environmental management.

    PubMed

    Sha, Jian; Liu, Min; Wang, Dong; Swaney, Dennis P; Wang, Yuqiu

    2013-07-30

    Models and related analytical methods are critical tools for use in modern watershed management. A modeling approach for quantifying the source apportionment of dissolved nitrogen (DN) and associated tools for examining the sensitivity and uncertainty of the model estimates were assessed for the Sha He River (SHR) watershed in China. The Regional Nutrient Management model (ReNuMa) was used to infer the primary sources of DN in the SHR watershed. This model is based on the Generalized Watershed Loading Functions (GWLF) and the Net Anthropogenic Nutrient Input (NANI) framework, modified to improve the characterization of subsurface hydrology and septic system loads. Hydrochemical processes of the SHR watershed, including streamflow, DN load fluxes, and corresponding DN concentration responses, were simulated following calibrations against observations of streamflow and DN fluxes. Uncertainty analyses were conducted with a Monte Carlo analysis to vary model parameters for assessing the associated variations in model outputs. The model performed accurately at the watershed scale and provided estimates of monthly streamflows and nutrient loads as well as DN source apportionments. The simulations identified the dominant contribution of agricultural land use and significant monthly variations. These results provide valuable support for science-based watershed management decisions and indicate the utility of ReNuMa for such applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome

    PubMed Central

    Heinen, Markus; Hettich, Moritz M.; Ryan, Devon P.; Schnell, Susanne; Paesler, Katharina; Ehninger, Dan

    2012-01-01

    Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAA receptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAA receptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome. PMID:22848851

  16. Bubble growth as a means to measure dissolved nitrogen concentration in aerated water

    NASA Astrophysics Data System (ADS)

    Ando, Keita; Yamashita, Tatsuya

    2017-11-01

    Controlling the amount of dissolved gases in water is important, for example, to food processing; it is essential to quantitatively evaluate dissolved gas concentration. The concentration of dissolved oxygen (DO) can be measured by commercial DO meters, but that of dissolved nitrogen (DN) cannot be obtained easily. Here, we propose a means to measure DN concentration based on Epstein-Plesset-type analysis of bubble growth under dissolved gas supersaturation. DO supersaturation in water is produced by oxygen microbubble aeration. The diffusion-driven growth of bubbles nucleated at glass surfaces in contact with the aerated water is first observed. The observed growth is then compared to the extended Epstein-Plesset theory that considers Fick's mass transfer of both DO and DN across bubble interfaces; in this comparison, the unknown DN concentration is treated as a fitting parameter. Comparisons between the experiment and the theory suggest, as expected, that DN can be effectively purged by oxygen microbubble aeration. This study was supported in part by the Mizuho Foundation for the Promotion of Science and by a MEXT Grant-in-Aid for the Program for Leading Graduate Schools.

  17. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

    PubMed

    Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

    2014-09-01

    Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

  18. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system

    PubMed Central

    Mogensen, Carl Erik; Schernthaner, Gerit-Holger

    2014-01-01

    Diabetic nephropathy (DN) affects an estimated 20%–40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. PMID:25116004

  19. Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy: Fact or Fiction?

    PubMed

    Loeffler, Ivonne; Wolf, Gunter

    2015-10-09

    The pathophysiology of diabetic nephropathy (DN), one of the most serious complications in diabetic patients and the leading cause of end-stage renal disease worldwide, is complex and not fully elucidated. A typical hallmark of DN is the excessive deposition of extracellular matrix (ECM) proteins in the glomerulus and in the renal tubulointerstitium, eventually leading to glomerulosclerosis and interstitial fibrosis. Although it is obvious that myofibroblasts play a major role in the synthesis and secretion of ECM, the origin of myofibroblasts in DN remains the subject of controversial debates. A number of studies have focused on epithelial-to-mesenchymal transition (EMT) as one source of matrix-generating fibroblasts in the diseased kidney. EMT is characterized by the acquisition of mesenchymal properties by epithelial cells, preferentially proximal tubular cells and podocytes. In this review we comprehensively review the literature and discuss arguments both for and against a function of EMT in renal fibrosis in DN. While the precise extent of the contribution to nephrotic fibrosis is certainly arduous to quantify, the picture that emerges from this extensive body of literature suggests EMT as a major source of myofibroblasts in DN.

  20. Process for the conversion of lower alcohols to higher branched oxygenates

    DOEpatents

    Barger, Paul T.

    1996-01-01

    A process is provided for the production of branched C.sub.4+ oxygenates from lower alcohols such as methanol, ethanol, propanol and mixtures thereof. The process comprises contacting the lower alcohols with a solid catalyst comprising a mixed metal oxide support having components selected from the group consisting of oxides of zinc, magnesium, zirconia, titanium, manganese, chromium, and lanthanides, and an activation metal selected from the group consisting of Group VIII metal, Group IB metals, and mixtures thereof. The advantage of the process is improved yields and selectivity to isobutanol which can subsequently be employed in the production of high octane motor gasoline.

  1. Process for the conversion of lower alcohols to higher branched oxygenates

    DOEpatents

    Barger, P.T.

    1996-09-24

    A process is provided for the production of branched C{sub x} oxygenates from lower alcohols such as methanol, ethanol, propanol and mixtures thereof. The process comprises contacting the lower alcohols with a solid catalyst comprising a mixed metal oxide support having components selected from the group consisting of oxides of zinc, magnesium, zirconia, titanium, manganese, chromium, and lanthanides, and an activation metal selected from the group consisting of Group VIII metal, Group IB metals, and mixtures thereof. The advantage of the process is improved yields and selectivity to isobutanol which can subsequently be employed in the production of high octane motor gasoline.

  2. Variations in CCR5, but not HFE, ELMO1, or SLC12A3, are associated with susceptibility to kidney disease in north Indian individuals with type 2 diabetes.

    PubMed

    Yadav, Ashok K; Kumar, Vinod; Dutta, Pinaki; Bhansali, Anil; Jha, Vivekanand

    2014-11-01

    Diabetic nephropathy (DN), the leading cause of end-stage renal disease worldwide, may have a genetic component. In the present study, we investigated variations in a set of genes with susceptibility to DN in a north Indian population. Four genes (HFE, ELMO1, SLC12A3, and CCR5) were selected on the basis of reported association with type 2 diabetes and nephropathy. In all, 417 diabetic subjects (215 without kidney disease [DM] and 202 with DN) and 197 healthy controls (HC) were evaluated for variations in HFE (845 G>A and 187G>C), SLC12A3 (g.34372G>A), CCR5 (59029A>G), and ELMO1 (+9170 G>A). Polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism and Taqman allele discrimination assays. Significant differences were found in genotype and allelic frequency in SLC12A3 (g.34372G>A) between diabetic subjects and HC (P < 0.03). There were no differences in the SLC12A3 g.34372G>A (AA+GA) genotype between diabetic subjects with and without nephropathy. However, the CCR5 59029AA genotype and A allele were significantly more frequent in diabetics compared with the HC (P = 0.01 and 0.03, respectively) and subjects with DN versus DM (P = 0.002 and 0.01, respectively). For ELMO1 (+9170 G>A), the GG genotype frequency was higher in the diabetic versus HC group. There were no differences in the frequency of HFE-845 G>A and HFE-187G>C among the groups. This study shows that the CCR5 AA genotype is over-represented in subjects with kidney disease due to type 2 diabetes. The CCR5 59029G>A and ELMO1 (+9170 G>A) loci are more frequent, and the SLC12A3 34372 AA genotype is associated with a reduced risk of diabetes. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  3. Integrity of the Linker of Nucleoskeleton and Cytoskeleton Is Required for Efficient Herpesvirus Nuclear Egress.

    PubMed

    Klupp, Barbara G; Hellberg, Teresa; Granzow, Harald; Franzke, Kati; Dominguez Gonzalez, Beatriz; Goodchild, Rose E; Mettenleiter, Thomas C

    2017-10-01

    Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes. The linker of nucleoskeleton and cytoskeleton (LINC) complex consists of INM proteins with a luminal SUN (Sad1/UNC-84 homology) domain connected to ONM proteins with a KASH (Klarsicht, ANC-1, SYNE homology) domain and is thought to be responsible for spacing the nuclear membranes. To investigate the role of the LINC complex during herpesvirus infection, we generated cell lines constitutively expressing dominant negative (dn) forms of SUN1 and SUN2. Ultrastructural analyses revealed a significant expansion of the PNS and the contiguous intracytoplasmic lumen, most likely representing endoplasmic reticulum (ER), especially in cells expressing dn-SUN2. After infection, primary virions accumulated in these expanded luminal regions, also very distant from the nucleus. The importance of the LINC complex was also confirmed by reduced progeny virus titers in cells expressing dn-SUN2. These data show that the intact LINC complex is required for efficient nuclear egress of herpesviruses, likely acting to promote fusion of primary enveloped virions with the ONM. IMPORTANCE While the viral factors for primary envelopment of nucleocapsids at the inner nuclear membrane are known to the point of high-resolution structures, the roles of cellular components and regulators remain enigmatic. Furthermore, the machinery responsible for fusion with the outer nuclear membrane is unsolved. We show here that dominant negative SUN2 interferes with efficient herpesvirus nuclear egress, apparently by interfering with fusion between the primary virion envelope and outer nuclear membrane. This identifies a new cellular component important for viral egress and implicates LINC complex integrity in nonconventional nuclear membrane trafficking. Copyright © 2017 American Society for Microbiology.

  4. Probing dissolved organic matter in the critical zone: a comparison between in situ sampling and aqueous soil extracts

    NASA Astrophysics Data System (ADS)

    Perdrial, J. N.; Perdrial, N.; Harpold, A. A.; Peterson, A. M.; Vasquez, A.; Chorover, J.

    2011-12-01

    Analyzing dissolved organic matter (DOM) of soil solution constitutes an integral activity in critical zone science as important insights to nutrient and carbon cycling and mineral weathering processes can be gained. Soil solution can be obtained by a variety of approaches such as by in situ zero-tension and tension samplers or by performing soil extracts in the lab. It is generally preferred to obtain soil solution in situ with the least amount of disturbance. However, in water limited environments, such as in southwestern US, in situ sampling is only possible during few hydrologic events and soil extracts are often employed. In order to evaluate the performance of different sampling approaches for OM analysis, results from aqueous soil extracts were compared with in situ samples obtained from suction cups and passive capillary wick samplers (PCAP's). Soil from an OA-horizon of mixed conifer forest Jemez River Basin Critical Zone Observatory (JRB-CZO) in NM was sampled twice and in situ samples from co-located suction cups and PCAPs were collected 7 times during the 2011 snowmelt period. Dissolved organic carbon and nitrogen concentrations (DOC and DN) as well as OM quality (FTIR, fluorescence spectroscopy and PARAFAC) were analyzed. The aqueous soil extracts (solid:solution = 1:5 mass basis) showed highest DOC and lowest DN concentrations whereas samples collected in-situ had lower DOC and higher DN concentrations. PARAFAC analysis using a four component model showed a dominance of fluorescence in region I and II (protein-like fluorescence) for samples collected in situ indicating the presence of more bio-molecules (proteins). In contrast, the dominant PARAFAC component of the soil extract was found in region 3 (fulvic acid-like fluorescence). FTIR analysis showed high intensity band at 1600 cm-1 in the case of the aqueous soil extract that correspond to asymmetric stretching of carboxyl groups. These preliminary results indicate that aqueous soil extracts likely lead to the underestimation of the amount of biomolecules and the overestimation of fulvic acid contents of soil solutions.

  5. 47 CFR 64.2003 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RULES RELATING TO COMMON CARRIERS Customer Proprietary Network Information § 64.2003 Definitions. (a) Account information. “Account information” is information that is specifically connected to the customer's service relationship with the carrier, including such things as an account number or any component thereof...

  6. 29 CFR 1983.101 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) PROCEDURES FOR THE HANDLING OF RETALIATION COMPLAINTS UNDER SECTION 219 OF THE CONSUMER PRODUCT SAFETY... other than Saturdays, Sundays, and Federal holidays. (c) Commission means the Consumer Product Safety... filed. (e) (1) Consumer product means any article, or component part thereof, produced or distributed...

  7. 29 CFR 1983.101 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) PROCEDURES FOR THE HANDLING OF RETALIATION COMPLAINTS UNDER SECTION 219 OF THE CONSUMER PRODUCT SAFETY... other than Saturdays, Sundays, and Federal holidays. (c) Commission means the Consumer Product Safety... filed. (e) (1) Consumer product means any article, or component part thereof, produced or distributed...

  8. 77 FR 66632 - Certain Protective Cases and Components Thereof; Notice of the Commission's Final Determination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... ''); Anbess Electronics Co. Ltd. of Schenzhen, China (``Anbess''); Cellairis Franchise, Inc. of Alpharetta... also found that the importation requirements of section 337 (19 U.S.C. 1337(a)(1)(B), (C)) have been...

  9. 48 CFR 225.7002-1 - Restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... grown, reprocessed, reused, or produced in the United States: (1) Food. (2) Clothing and the materials... associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery, handwear, belts, badges, and insignia. For additional...

  10. 48 CFR 225.7002-1 - Restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... grown, reprocessed, reused, or produced in the United States: (1) Food. (2) Clothing and the materials... associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery, handwear, belts, badges, and insignia. For additional...

  11. 48 CFR 225.7002-1 - Restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... grown, reprocessed, reused, or produced in the United States: (1) Food. (2) Clothing and the materials... associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery, handwear, belts, badges, and insignia. For additional...

  12. 48 CFR 225.7002-1 - Restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... grown, reprocessed, reused, or produced in the United States: (1) Food. (2) Clothing and the materials... associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery, handwear, belts, badges, and insignia. For additional...

  13. 48 CFR 225.7002-1 - Restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... grown, reprocessed, reused, or produced in the United States: (1) Food. (2) Clothing and the materials... associated with, clothing and the materials and components thereof. Clothing includes items such as outerwear, headwear, underwear, nightwear, footwear, hosiery, handwear, belts, badges, and insignia. For additional...

  14. 28 CFR 22.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Administration DEPARTMENT OF JUSTICE CONFIDENTIALITY OF IDENTIFIABLE RESEARCH AND STATISTICAL INFORMATION § 22.2... capacity. (c) Research or statistical project means any program, project, or component thereof which is... statistical information means any information which is collected during the conduct of a research or...

  15. 28 CFR 22.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Administration DEPARTMENT OF JUSTICE CONFIDENTIALITY OF IDENTIFIABLE RESEARCH AND STATISTICAL INFORMATION § 22.2... capacity. (c) Research or statistical project means any program, project, or component thereof which is... statistical information means any information which is collected during the conduct of a research or...

  16. 75 FR 45663 - In the Matter of: Certain Inkjet Ink Supplies and Components Thereof; Corrected Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... International, 10 C, Garden Building, No. 1083 JiuZhou Road, Jida, Zhuhai, Guangdong, China 519015; Ourway Image... 20436; and (3) For the investigation so instituted, the Honorable Paul J. Luckern, Chief Administrative...

  17. Spectroscopic Classification of ASASSN-13dn

    NASA Astrophysics Data System (ADS)

    Martini, P.; Elias, J.; Points, S.; Prieto, J. L.; Shappee, B. J.; Stanek, K. Z.; Kochanek, C. S.; Holoien, T. W.-S.; Jencson, J.; Basu, U.; Beacom, J. F.; Szczygiel, D.; Pojmanski, G.; Brimacombe, J.; Bersier, D.

    2013-12-01

    We obtained optical spectra of ASASSN-13dn (ATel #5665). The candidate was confirmed with the new KOSMOS instrument (Kitt Peak Ohio State Multi-Object Spectrograph), which is presently being commissioned at the KPNO 4-m Mayall telescope. Observations were obtained with both the blue and red VPH grisms (50 min each) for a combined wavelength range of 380nm to 965nm at R ~ 2000. The spectrum of ASASSN-13dn is characteristic of a Type II SN at the redshift of its host galaxy (z=0.023).

  18. Exaggerated NMDA Mediated LTD in a Mouse Model of Down Syndrome and Pharmacological Rescuing by Memantine

    ERIC Educational Resources Information Center

    Scott-McKean, Jonah J.; Costa, Alberto C. S.

    2011-01-01

    The Ts65Dn mouse is the best-studied animal model for Down syndrome. In the experiments described here, NMDA-mediated or mGluR-mediated LTD was induced in the CA1 region of hippocampal slices from Ts65Dn and euploid control mice by bath application of 20 [mu]M NMDA for 3 min and 50 [mu]M DHPG for 5 min, respectively. We found that Ts65Dn mice…

  19. Thick film magnetic nanoparticulate composites and method of manufacture thereof

    NASA Technical Reports Server (NTRS)

    Ge, Shihui (Inventor); Yan, Dajing (Inventor); Xiao, Danny T. (Inventor); Ma, Xinqing (Inventor); Zhang, Yide (Inventor); Zhang, Zongtao (Inventor)

    2009-01-01

    Thick film magnetic/insulating nanocomposite materials, with significantly reduced core loss, and their manufacture are described. The insulator coated magnetic nanocomposite comprises one or more magnetic components, and an insulating component. The magnetic component comprises nanometer scale particles (about 1 to about 100 nanometers) coated by a thin-layered insulating phase. While the intergrain interaction between the immediate neighboring magnetic nanoparticles separated by the insulating phase provides the desired soft magnetic properties, the insulating material provides high resistivity, which reduces eddy current loss.

  20. Analysis of the Drosophila Clock promoter reveals heterogeneity in expression between subgroups of central oscillator cells and identifies a novel enhancer region.

    PubMed

    Gummadova, Jennet Orazmuradovna; Coutts, Graham Andrew; Glossop, Nicholas Robert John

    2009-10-01

    The CLOCK-CYCLE (CLK-CYC) heterodimer lies at the heart of the circadian oscillator mechanism in Drosophila, yet little is known about the identity of transcription factors that regulate the expression of Clk and/or cyc. Here, the authors have used a transgenic approach to isolate regions of the Clk locus that are necessary for expression in central oscillator neurons in the adult fly brain. This analysis shows that central clock cells can be subdivided into 2 distinct groups based on Clk gene regulation. Expression in the lateral neuron (LN), dorsal neuron 1 anterior (DN1a) and 2 (DN2) clusters requires cis-elements located in a 122 base-pair (bp) region (-206 to -84) of the Clk promoter. Expression in the remaining dorsal neurons, 1 posterior (DN1p) and 3 (DN3) and the lateral posterior neurons (LPN), requires regulatory elements located in the -856 to -206 region. In addition, expression in photoreceptors of the compound eye is enhanced by cis-elements located in a 3rd region of the Clk locus (-1982 to -856). This region also enhances expression in nonoscillator cells in the brain including the Kenyon cells, but expression in these neurons is suppressed by regulatory sites located further upstream of -1982. The authors' analysis reveals clear heterogeneity in Clk gene expression in the adult brain and provides a necessary focus to isolate novel transcription factors that bind at the Clk locus to regulate expression in different oscillator neuron subgroups. These results also suggest that the DN1a/DN2 neurons may have more molecular commonality with the LNs than they do with the DN1p/DN3/LPN neurons. Finally, this analysis has generated new transgenic lines that will enable genes to be misexpressed in subgroups of central oscillator cells that have previously been resistant to discrete genetic manipulation. Hence, these lines provide important new tools to facilitate a more complete dissection of the neural network that regulates output rhythms in physiology and behavior.

  1. Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation.

    PubMed

    Cole, Robert Townsend; Gandhi, Jonathan; Bray, Robert A; Gebel, Howard M; Yin, Michael; Shekiladze, Nikolaz; Young, An; Grant, Aubrey; Mahoney, Ian; Laskar, S Raja; Gupta, Divya; Bhatt, Kunal; Book, Wendy; Smith, Andrew; Nguyen, Duc; Vega, J David; Morris, Alanna A

    2018-04-01

    Despite improvements in outcomes after heart transplantation, black recipients have worse survival compared with non-black recipients. The source of such disparate outcomes remains largely unknown. We hypothesize that a propensity to generate de-novo donor-specific antibodies (dnDSA) and subsequent antibody-mediated rejection (AMR) may account for racial differences in sub-optimal outcomes after heart transplant. In this study we aimed to determine the role of dnDSA and AMR in racial disparities in post-transplant outcomes. This study was a single-center, retrospective analysis of 137 heart transplant recipients (81% male, 48% black) discharged from Emory University Hospital. Patients were classified as black vs non-black for the purpose of our analysis. Kaplan-Meier and Cox regression analyses were used to evaluate the association between race and selected outcomes. The primary outcome was the development of dnDSA. Secondary outcomes included treated AMR and a composite of all-cause graft dysfunction or death. After 3.7 years of follow-up, 39 (28.5%) patients developed dnDSA and 19 (13.8%) were treated for AMR. In multivariable models, black race was associated with a higher risk of developing dnDSA (hazard ratio [HR] 3.65, 95% confidence interval [CI] 1.54 to 8.65, p = 0.003) and a higher risk of treated AMR (HR 4.86, 95% CI 1.26 to 18.72, p = 0.021) compared with non-black race. Black race was also associated with a higher risk of all-cause graft dysfunction or death in univariate analyses (HR 2.10, 95% CI 1.02 to 4.30, p = 0.044). However, in a multivariable model incorporating dnDSA, black race was no longer a significant risk factor. Only dnDSA development was significantly associated with all-cause graft dysfunction or death (HR 4.85, 95% CI 1.89 to 12.44, p = 0.001). Black transplant recipients are at higher risk for the development of dnDSA and treated AMR, which may account for racial disparities in outcomes after heart transplantation. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Fatigue, insomnia and nervousness: gender disparities and roles of individual characteristics and lifestyle factors among economically active people.

    PubMed

    Peretti-Watel, Patrick; Legleye, Stéphane; Baumann, Michèle; Choquet, Marie; Falissard, Bruno; Chau, Nearkasen

    2009-09-01

    Individuals with certain personal, family and job characteristics are at elevated risk of poor mental health. Yet, the respective role of obesity, smoking, alcohol abuse, low education, income, living and family conditions, and socio-occupational category in fatigue/insomnia (FI), nervousness (N) and frequent drug use for those disorders (DFI and DN) among men and women and in gender disparities are not well known. We studied gender differences in FI, N, DFI, DN, and in their correlated, and whether the gender differences were mediated by individual and lifestyle factors among 3,450 active subjects aged 18-64, randomly selected from North-eastern France. Subjects completed a post-mailed questionnaire. Data were analyzed via adjusted odds ratio (ORa) computed with the logistic regression model. Women were more affected than men for FI (21.3 vs. 13.1%, OR adjusted for age ORa 1.80, 95% CI 1.50-2.16), DFI (11.6 vs. 7.1%, ORa 1.74, 1.38-2.21), N (14.7 vs. 9.9%, ORa 1.58, 1.28-1.94), and for DN (12.1 vs. 5.7%, ORa 2.29, 1.79-2.94). These differences were not mediated by the individual characteristics studied. Multivariate analysis showed that the risk patterns varied between the two sexes. Smoking was related to N in men as well as in women; alcohol abuse to DFI in men only; lack of family support to all outcome variables in men and women; low educational level to DFI in men only; low income to FI, N and DN in men and to FI and DN in women; being unmarried to DN in men; being divorced/separated to N and DN in women; being a manual worker to FI and being a farmer to DFI in men; and being a manual worker to DN and being an employee to FI in women (1.50

  3. Toward improved target conformity for two spot scanning proton therapy delivery systems using dynamic collimation

    PubMed Central

    Moignier, Alexandra; Gelover, Edgar; Smith, Blake R.; Wang, Dongxu; Flynn, Ryan T.; Kirk, Maura L.; Lin, Liyong; Solberg, Timothy D.; Lin, Alexander; Hyer, Daniel E.

    2016-01-01

    Purpose: To quantify improvement in target conformity in brain and head and neck tumor treatments resulting from the use of a dynamic collimation system (DCS) with two spot scanning proton therapy delivery systems (universal nozzle, UN, and dedicated nozzle, DN) with median spot sizes of 5.2 and 3.2 mm over a range of energies from 100 to 230 MeV. Methods: Uncollimated and collimated plans were calculated with both UN and DN beam models implemented within our in-house treatment planning system for five brain and ten head and neck datasets in patients previously treated with spot scanning proton therapy. The prescription dose and beam angles from the clinical plans were used for both the UN and DN plans. The average reduction of the mean dose to the 10-mm ring surrounding the target between the uncollimated and collimated plans was calculated for the UN and the DN. Target conformity was analyzed using the mean dose to 1-mm thickness rings surrounding the target at increasing distances ranging from 1 to 10 mm. Results: The average reductions of the 10-mm ring mean dose for the UN and DN plans were 13.7% (95% CI: 11.6%–15.7%; p < 0.0001) and 11.5% (95% CI: 9.5%–13.5%; p < 0.0001) across all brain cases and 7.1% (95% CI: 4.4%–9.8%; p < 0.001) and 6.3% (95% CI: 3.7%–9.0%; p < 0.001), respectively, across all head and neck cases. The collimated UN plans were either more conformal (all brain cases and 60% of the head and neck cases) than or equivalent (40% of the head and neck cases) to the uncollimated DN plans. The collimated DN plans offered the highest conformity. Conclusions: The DCS added either to the UN or DN improved the target conformity. The DCS may be of particular interest for sites with UN systems looking for a more economical solution than upgrading the nozzle to improve the target conformity of their spot scanning proton therapy system. PMID:26936726

  4. Differential presentation and survival of de novo and recurrent metastatic breast cancer over time: 1990-2010.

    PubMed

    Malmgren, Judith A; Mayer, Musa; Atwood, Mary K; Kaplan, Henry G

    2018-01-01

    Differences in de novo (dnMBC) and recurrent metastatic breast cancer (rMBC) presentation and survival over time have not been adequately described. A retrospective cohort study, 1990-2010, with follow up through 2015 of dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distant metastatic recurrence (stage I-III initial diagnosis) [dnMBC = 247, rMBC = 911)]. Analysis included Chi squared tests of categorical variables, Kaplan-Meier survival estimates, and Cox proportional adjusted hazard ratios (HzR) and 95% confidence intervals (CI). Disease specific survival (DSS) was time from diagnosis or distant recurrence to BC death. Over time, 1990-1998, 1999-2004, and 2005-2010, dnMBC incidence was constant (3%) and rMBC incidence decreased [18% to 7% (p < 0.001)] with no change in dnMBC hormone receptor (HR) or her2-neu (HER2) status but a decrease in rMBC HER2-positive cases and increase in triple negative breast cancer (HR-negative/HER2-negative) (p = 0.049). Five-year dnMBC DSS was 44% vs. 21% for rMBC (p < 0.001). Five-year dnMBC DSS improved over time [28% to 55% (p = 0.008)] and rMBC worsened [23% to 13%, p = 0.065)]. Worse DSS was associated with HR-negative status (HzR = 1.63; 1.41, 1.89), rMBC (HzR = 1.88; 1.58, 2.23), older age (70 +) (HzR = 1.88; 1.58, 2.24), > 1 distant metastases (HzR 1.39; 1.20, 1.62), and visceral dominant disease (HzR 1.22; 1.05, 1.43). After 1998, HER2-positive disease was associated with better DSS (HzR = 0.72, 95% CI 0.56, 0.93). Factors associated with the widening survival gap and non-equivalence between dnMBC and rMBC and decreased rMBC incidence warrant further study.

  5. CD4-veCD8-ve CD30+ve T cells are detectable in human lung transplant patients and their proportion of the lymphocyte population after in vitro stimulation with donor spleen cells correlates with preservation of lung physiology.

    PubMed

    Polster, K; Walker, A; Fildes, J; Entwistle, G; Yonan, N; Hutchinson, I V; Leonard, C T

    2005-06-01

    Survival following lung transplantation is less than 50% at 5 years, mainly due to immune-mediated chronic rejection. Recently a novel subset of T cells, CD4-veCD8-ve CD30+ve, so-called double negative (DN) CD30+ve T cells, has been described and shown to be responsible for tolerance in an animal model of skin transplantation. We investigated 18 lung transplant recipients for the presence of DN CD30+ve T cells in resting peripheral blood and also following in vitro stimulation of recipient peripheral blood mononuclear cells (PBMCs) with donor spleen cells. Small percentages (0.2% to 6%) of DN T cells are detectable in resting PBMCs of human transplant patients (n = 18), but these did not correlate with allograft function, acute rejection episodes, HLA mismatch, or CMV status. On repeated stimulation of recipient PBMCs (two exposures) in vitro by donor spleen cells (2:1 ratio stimulators to responders) the percentage of DN CD30+ve T cells within the lymphocyte pool correlated with preservation of allograft lung function (both for FEV(1), P = .009, and FEF(25-75), P = .036) and was inversely correlated with grade of chronic rejection. On repeated exposure of recipient PBMCs to donor spleen cells with a 1:1 ratio the percentage of DN CD30+ve T cells correlated with the number of acute rejection episodes of grade 2 or greater. The total number of HLA mismatches correlated with the percentage DN CD30+ve T cells present after primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio). The number of mismatches at the B locus inversely correlated with the percentage of DN CD30+ve T cells after primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio; P = .031, n = 18). Percentages of DN CD30+ve T cells present following repeated stimulation of recipient PBMCs by donor spleen cells correlated with preservation of graft function following lung transplantation.

  6. Catalysts for the hydrodenitrogenation of organic materials and process for the preparation of the catalysts

    DOEpatents

    Laine, R.M.; Hirschon, A.S.; Wilson, R.B. Jr.

    1987-12-29

    A process is described for the preparation of a multimetallic catalyst for the hydrodenitrogenation of an organic feedstock, which process comprises: (a) forming a precatalyst itself comprising: (1) a first metal compound selected from compounds of nickel, cobalt or mixtures thereof; (2) a second metal compound selected from compounds of chromium, molybdenum, tungsten, or mixtures thereof; and (3) an inorganic support; (b) heating the precatalyst of step (a) with a source of sulfide in a first non-oxidizing gas at a temperature and for a time effective to presulfide the precatalyst; (c) adding in a second non-oxidizing gas to the sulfided precatalyst of step (b) an organometallic transition metal moiety selected from compounds of iridium, rhodium, iron, ruthenium, tungsten or mixtures thereof for a time and at a temperature effective to chemically combine the metal components; and (d) optionally heating the chemically combined catalyst of step (b) in vacuum at a temperature and for a time effective to remove residual volatile organic materials. 12 figs.

  7. 77 FR 1504 - Certain Kinesiotherapy Devices and Components Thereof; Notice of Institution of Investigation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-10

    .... Lover's Lane & Co., 46750 Port St., Plymouth, MI 48170-6031. PHE, Inc. d/b/a Adam & Eve, 302 Meadowland.... Mile Inc. d/b/a Lion's Den Adult, 110 East Wilson Bridge Road, Suite 110, Worthington, OH 43085...

  8. Bonded polyimide fuel cell package and method thereof

    DOEpatents

    Morse, Jeffrey D.; Jankowski, Alan; Graff, Robert T.; Bettencourt, Kerry

    2005-11-01

    Described herein are processes for fabricating microfluidic fuel cell systems with embedded components in which micron-scale features are formed by bonding layers of DuPont Kapton.TM. polyimide laminate. A microfluidic fuel cell system fabricated using this process is also described.

  9. 78 FR 64009 - Certain Optical Disc Drives, Components Thereof, and Products Containing the Same; Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... Cliffs, NJ 07632. Nintendo Co., Ltd., 11-1 Hokotate-cho, Kamitoba, Minami-ku, Kyoto 601- 8501, Japan. Nintendo of America, Inc., 4600 150th Avenue NE, Redmond, WA 98052- 5113. Panasonic Corp., 1006, Oaza...

  10. 10 CFR 436.11 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... significantly the cost of energy consumed. Building water system means a water conservation measure or any... building means an energy or water conservation measure or any building, structure, or facility, or part... water conservation measure, or any component thereof. Retrofit means installation of a building energy...

  11. 10 CFR 436.11 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... significantly the cost of energy consumed. Building water system means a water conservation measure or any... building means an energy or water conservation measure or any building, structure, or facility, or part... water conservation measure, or any component thereof. Retrofit means installation of a building energy...

  12. 10 CFR 436.11 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... significantly the cost of energy consumed. Building water system means a water conservation measure or any... building means an energy or water conservation measure or any building, structure, or facility, or part... water conservation measure, or any component thereof. Retrofit means installation of a building energy...

  13. 76 FR 4374 - Certain Digital Televisions And Components Thereof; Notice of Commission Determination Not To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... Irvine, California, AmTRAN Technology Co., Ltd. of Taipei, Taiwan and AmTRAN Logistic, Inc. of Irvine... 210.42(h) of the Commission's Rules of Practice and Procedure (19 CFR 210.42(h)). Issued: January 19...

  14. 76 FR 73677 - Investigations: Terminations, Modifications and Rulings: Certain Electronic Devices With Image...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-724] Investigations: Terminations, Modifications and Rulings: Certain Electronic Devices With Image Processing Systems, Components Thereof, and Associated Software AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby...

  15. 78 FR 35050 - Certain Windshield Wiper Devices and Components Thereof; Notice of Institution of Investigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ... notice of investigation will not be granted unless good cause therefor is shown. Failure of a respondent... constitute a waiver of the right to appear and contest the allegations of the complaint and this notice, and...

  16. 32 CFR 310.44 - Inspection reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) PRIVACY PROGRAM DOD PRIVACY PROGRAM Inspections § 310.44 Inspection reporting. (a) Document the findings of the... appropriate, shall reflect overall assets of the Component Privacy Program inspected, or portion thereof...

  17. 49 CFR 831.9 - Authority of Board representatives.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Authority of Board representatives. 831.9 Section 831.9 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL TRANSPORTATION... Government agency, or person having possession or control of any transportation vehicle or component thereof...

  18. 75 FR 32971 - In the Matter of Certain Inkjet Ink Supplies and Components Thereof; Notice of Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    ... Shanghai, China; SmartOne Services LLC d/b/a InkForSale.net of Hayward, California; Shenzhen Print Media Co., Ltd. of Shenzhen, China; Comptree of City of Industry, California; Zhuhai National Resources & Jingjie...

  19. Comminuting irradiated ferritic steel

    DOEpatents

    Bauer, Roger E.; Straalsund, Jerry L.; Chin, Bryan A.

    1985-01-01

    Disclosed is a method of comminuting irradiated ferritic steel by placing the steel in a solution of a compound selected from the group consisting of sulfamic acid, bisulfate, and mixtures thereof. The ferritic steel is used as cladding on nuclear fuel rods or other irradiated components.

  20. Proteome and Antigens of Mycobacterium avium subspecies Paratuberculosis

    USDA-ARS?s Scientific Manuscript database

    This chapter will review what is known about the proteome of this significant veterinary pathogen by discussing the use of various whole cell preparations and fractionated components thereof. With improvements in technology, many new modifications to the traditional ELISA assay have been introduced...

  1. Semaphorin3a Promotes Advanced Diabetic Nephropathy

    PubMed Central

    Aggarwal, Pardeep K.; Veron, Delma; Thomas, David B.; Siegel, Dionicio; Moeckel, Gilbert; Kashgarian, Michael

    2015-01-01

    The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes. Excess sema3a disrupts the glomerular filtration barrier. Here, using immunohistochemistry, we show increased podocyte SEMA3A in renal biopsies from patients with advanced DN. Using inducible, podocyte-specific Sema3a gain-of-function (Sema3a+) mice made diabetic with streptozotocin, we demonstrate that sema3a is pathogenic in DN. Diabetic Sema3a+ mice develop massive proteinuria, renal insufficiency, and extensive nodular glomerulosclerosis, mimicking advanced DN in humans. In diabetic mice, Sema3a+ exacerbates laminin and collagen IV accumulation in Kimmelstiel-Wilson-like glomerular nodules and causes diffuse podocyte foot process effacement and F-actin collapse via nephrin, αvβ3 integrin, and MICAL1 interactions with plexinA1. MICAL1 knockdown and sema3a inhibition render podocytes not susceptible to sema3a-induced shape changes, indicating that MICAL1 mediates sema3a-induced podocyte F-actin collapse. Moreover, sema3a binding inhibition or podocyte-specific plexinA1 deletion markedly ameliorates albuminuria and abrogates renal insufficiency and the diabetic nodular glomerulosclerosis phenotype of diabetic Sema3a+ mice. Collectively, these findings indicate that excess sema3a promotes severe diabetic nephropathy and identifies novel potential therapeutic targets for DN. PMID:25475434

  2. Evaluation of genetic association and expression reduction of TRPC1 in the development of diabetic nephropathy.

    PubMed

    Zhang, Dongying; Freedman, Barry I; Flekac, Milan; Santos, Elisabete; Hicks, Pamela J; Bowden, Donald W; Efendic, Suad; Brismar, Kerstin; Gu, Harvest F

    2009-01-01

    The TRPC1 gene on chromosome 3q22-24 resides within the linkage region for diabetic nephropathy (DN) in type 1 (T1D) and type 2 diabetes mellitus (T2D). A recent study has demonstrated that TRPC1 expression is reduced in the kidney of diabetic ZDF- and STZ-treated rats. The present study aimed to evaluate the genetic and functional role of TRPC1 in the development of DN. Genetic association study was performed with two independent cohorts, including 1,177 T1D European Americans with or without DN from GoKinD population and 850 African-American subjects with T2D-associated end-stage renal disease (ESRD), or with hypertensive (non-diabetic) ESRD, and nondiabetic controls. Seven tag SNP markers derived from HapMap data (phase II) were genotyped. TRPC1 gene expression was examined using real time RT-PCR. No significant association of TRPC1 DNA polymorphisms with DN or ERSD was found in GoKinD and African-American populations. TRPC1 gene mRNA expression in kidney was found to be trendily reduced in 12-week and significantly in 26-week-old db/db mice. TRPC1 genetic polymorphism may not fundamentally contribute to the development of DN, while reduction of the gene expression in kidney may be a late phenomenon of DN as seen in diabetic animal models. 2008 S. Karger AG, Basel.

  3. Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

    PubMed Central

    Igo, Robert P.; Iyengar, Sudha K.; Nicholas, Susanne B.; Goddard, Katrina A.B.; Langefeld, Carl D.; Hanson, Robert L.; Duggirala, Ravindranath; Divers, Jasmin; Abboud, Hanna; Adler, Sharon G.; Arar, Nedal H.; Horvath, Amanda; Elston, Robert C.; Bowden, Donald W.; Guo, Xiuqing; Ipp, Eli; Kao, W.H. Linda; Kimmel, Paul L.; Knowler, William C.; Meoni, Lucy A.; Molineros, Julio; Nelson, Robert G.; Pahl, Madeline V.; Parekh, Rulan S.; Rasooly, Rebekah S.; Schelling, Jeffrey R.; Shah, Vallabh O.; Smith, Michael W.; Winkler, Cheryl A.; Zager, Philip G.; Sedor, John R.; Freedman, Barry I.

    2011-01-01

    Background Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. Methods A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Results Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10−5, LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. Conclusion These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. PMID:21454968

  4. Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson's disease.

    PubMed

    He, Naying; Huang, Pei; Ling, Huawei; Langley, Jason; Liu, Chunlei; Ding, Bei; Huang, Juan; Xu, Hongmin; Zhang, Yong; Zhang, Zhongping; Hu, Xiaoping; Chen, Shengdi; Yan, Fuhua

    2017-04-01

    Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron-rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor-dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0-T MR system. Inter-group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR-dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug-naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR-dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  5. A Water-Soluble Polyaniline Complex for Ink-Jet Printing of Optoelectronic Devices

    NASA Astrophysics Data System (ADS)

    Gribkova, O. L.; Saf'yanova, L. V.; Tameev, A. R.; Lypenko, D. A.; Tverskoi, V. A.; Nekrasov, A. A.

    2018-03-01

    The influence of the ratio of components in polyaniline (PANI) complexes with poly(sulfonic acid) on the viscosity of their aqueous solutions and electric conductivity of layers formed thereof. The optical properties and morphology of PANI complex layers formed by ink-jet printing have been studied. The optimum ratio of components to be used in anodic buffer layers for organic solar cells is determined.

  6. Component for thermoelectric generator

    DOEpatents

    Purdy, David L.

    1977-01-01

    In a thermoelectric generator, a component comprises a ceramic insulator, having over limited areas thereof, each area corresponding to a terminal end of thermoelectric wires, a coating of a first metal which adheres to the insulator, and an electrical thermoelectric junction including a second metal which wets said first metal and adheres to said terminal ends but does not wet said insulator, and a cloth composed of electrically insulating threads interlaced with thermoelectric wires.

  7. Switchable antifouling coatings and uses thereof

    DOEpatents

    Denton, Michele L. Baca; Dirk, Shawn M.; Johnson, Ross Stefan

    2017-02-28

    The present invention relates to antifouling coatings capable of being switched by using heat or ultraviolet light. Prior to switching, the coating includes an onium cation component having antimicrobial and antibacterial properties. Upon switching, the coating is converted to a conjugated polymer state, and the cationic component is released with any adsorbed biofilm layer. Thus, the coatings herein have switchable and releasable properties. Methods of making and using such coatings are also described.

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

    Kuncharin, Yanin; Sangphech, Naunpun; Kueanjinda, Patipark

    The Notch signaling pathway plays important roles in tumorigenesis in a context-dependent manner. In human cervical cancer, alterations in Notch signaling have been reported, and both tumor-suppressing and tumor-promoting roles of Notch signaling have been proposed; however, the precise molecular mechanisms governing these roles in cervical cancer remain controversial. MAML is a transcriptional co-activator originally identified by its role in Notch signaling. Recent evidence suggests that it also plays a role in other signaling pathways, such as the p53 and {beta}-catenin pathways. MAML is required for stable formation of Notch transcriptional complexes at the promoters of Notch target genes. Chromosomalmore » translocations affecting MAML have been shown to promote tumorigenesis. In this study, we used a truncated dominant-negative MAML1 (DN-MAML) to investigate the role of MAML in HPV-positive cervical cancer cell lines. Three human cervical cancer cell lines (HeLa, SiHa and CaSki) expressed all Notch receptors and the Notch target genes Hes1 and MAML1. Among these 3 cell lines, constitutive appearance of cleaved Notch1 was found only in CaSki cells, which suggests that Notch1 is constitutively activated in this cell line. Gamma secretase inhibitor (GSI) treatment, which suppresses Notch receptor activation, completely abrogated this form of Notch1 but had no effect on cell viability. Overexpression of DN-MAML by retroviral transduction in CaSki cells resulted in significant decreases in the mRNA levels of Hes1 and Notch1 but had no effects on the levels of MAML1, p53 or HPV E6/E7. DN-MAML expression induced increased viability of CaSki cells without any effect on cell cycle progression or cell proliferation. In addition, clonogenic assay experiments revealed that overexpression of DN-MAML resulted in increased colony formation compared to the overexpression of the control vector. When the status of the NF-{kappa}B pathway was investigated, CaSki cells overexpressing DN-MAML exhibited loss of phospho-I{kappa}B{alpha}, decreased total I{kappa}B{alpha} and nuclear localization of NF-{kappa}B p65, which suggests that the NF-{kappa}B pathway is hyperactivated. Furthermore, increased level of cleaved Notch1 was detected when DN-MAML was expressed. When DN-MAML-overexpressing cells were treated with GSI, significantly decreased cell viability was observed, indicating that inhibition of Notch signaling using GSI treatment and DN-MAML expression negatively affects cell viability. Taken together, targeting Notch signaling using DN-MAML and GSI treatment may present a novel method to control cell viability in cervical cancer cells.« less

  9. Relationship between fibrillin-1 genotype and severity of cardiovascular involvement in Marfan syndrome.

    PubMed

    Franken, Romy; Teixido-Tura, Gisela; Brion, Maria; Forteza, Alberto; Rodriguez-Palomares, Jose; Gutierrez, Laura; Garcia Dorado, David; Pals, Gerard; Mulder, Barbara Jm; Evangelista, Artur

    2017-11-01

    The effect of FBN1 mutation type on the severity of cardiovascular manifestations in patients with Marfan syndrome (MFS) has been reported with disparity results. This study aims to determine the impact of the FBN1 mutation type on aortic diameters, aortic dilation rates and on cardiovascular events (ie, aortic dissection and cardiovascular mortality). MFS patients with a pathogenic FBN1 mutation followed at two specialised units were included. FBN1 mutations were classified as being dominant negative (DN; incorporation of non-mutated and mutated fibrillin-1 in the extracellular matrix) or having haploinsufficiency (HI; only incorporation of non-mutated fibrillin-1, thus a decreased amount of fibrillin-1 protein). Aortic diameters and the aortic dilation rate at the level of the aortic root, ascending aorta, arch, descending thoracic aorta and abdominal aorta by echocardiography and clinical endpoints comprising dissection and death were compared between HI and DN patients. Two hundred and ninety patients with MFS were included: 113 (39%) with an HI- FBN1 mutation and 177 (61%) with a DN- FBN1 . At baseline, patients with HI- FBN1 had a larger aortic root diameter than patients with DN- FBN1 (HI: 39.3±7.2 mm vs DN: 37.3±6.8 mm, p=0.022), with no differences in age or body surface area. After a mean follow-up of 4.9±2.0 years, aortic root and ascending dilation rates were increased in patients with HI- FBN1 (HI: 0.57±0.8 vs DN: 0.28±0.5 mm/year, p=0.004 and HI: 0.59±0.9 vs DN: 0.30±0.7 mm/year, p=0.032, respectively). Furthermore, patients with HI- FBN1 tended to be at increased risk for the combined endpoint of dissection and death compared with patients with DN- FBN1 (HR: 3.3, 95% CI 1.0 to 11.4, p=0.060). Patients with an HI mutation had a more severely affected aortic phenotype, with larger aortic root diameters and a more rapid dilation rate, and tended to have an increased risk of death and dissections compared with patients with a DN mutation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

    PubMed

    Stringer, Megan; Abeysekera, Irushi; Thomas, Jared; LaCombe, Jonathan; Stancombe, Kailey; Stewart, Robert J; Dria, Karl J; Wallace, Joseph M; Goodlett, Charles R; Roper, Randall J

    2017-08-01

    Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis in the cerebellum. The lack of beneficial therapeutic behavioral effects and potentially detrimental skeletal effects of EGCG found in Ts65Dn mice emphasize the importance of identifying dosages of EGCG that reliably improve DS phenotypes and linking those effects to actions of EGCG (or EGCG-containing supplements) in specific targets in brain and bone. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Gene therapy of uterine leiomyomas: adenovirus-mediated expression of dominant negative estrogen receptor inhibits tumor growth in nude mice.

    PubMed

    Al-Hendy, Ayman; Lee, Eun J; Wang, Hui Q; Copland, John A

    2004-11-01

    Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management. This study was undertaken to investigate a potential therapy for leiomyoma; we used a mutated dominant-negative estrogen receptor gene delivered via an adenoviral vector (Ad-ER-DN). Ad-ER-DN transduction, in both human and rat leiomyoma cell lines, induced an increase in both caspase-3 levels and BAX/Bcl-2 ratio with evident apoptosis in the TdT-mediated dUTP nick-end labeling assay. In nude mice, rat leiomyoma cells ex vivo transduced with Ad-ER-DN supported significantly smaller tumors compared with Ad-LacZ-treated cells 5 weeks after implantation. In mice treated by direct intratumor injection into preexisting lesions, Ad-ER-DN caused immediate overall arrest of tumor growth. The Ad-ER-DN-treated tumors demonstrated severely inhibited cell proliferation (BrdU index) and a marked increase in the number of apoptotic cells (TdT-mediated dUTP nick-end labeling index). Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.

  12. Beyond a Gaussian Denoiser: Residual Learning of Deep CNN for Image Denoising.

    PubMed

    Zhang, Kai; Zuo, Wangmeng; Chen, Yunjin; Meng, Deyu; Zhang, Lei

    2017-07-01

    The discriminative model learning for image denoising has been recently attracting considerable attentions due to its favorable denoising performance. In this paper, we take one step forward by investigating the construction of feed-forward denoising convolutional neural networks (DnCNNs) to embrace the progress in very deep architecture, learning algorithm, and regularization method into image denoising. Specifically, residual learning and batch normalization are utilized to speed up the training process as well as boost the denoising performance. Different from the existing discriminative denoising models which usually train a specific model for additive white Gaussian noise at a certain noise level, our DnCNN model is able to handle Gaussian denoising with unknown noise level (i.e., blind Gaussian denoising). With the residual learning strategy, DnCNN implicitly removes the latent clean image in the hidden layers. This property motivates us to train a single DnCNN model to tackle with several general image denoising tasks, such as Gaussian denoising, single image super-resolution, and JPEG image deblocking. Our extensive experiments demonstrate that our DnCNN model can not only exhibit high effectiveness in several general image denoising tasks, but also be efficiently implemented by benefiting from GPU computing.

  13. Review of the origin of sulphur in DN-1 discharge and its implication for future development, Dauin prospect, central Philippines

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

    Bayrante, L.F.; Hermoso, D.Z.; Candelaria, M.R.

    1997-12-31

    Well DN-1, the first exploratory well of the Dauin geothermal prospect discharged in 1983 substantial quantities of sulphur with a near-neutral pH fluid (pH 6.4 to 7.2) containing maximum chloride levels of 3,300 mg/kg, SO{sub 4} of 300 mg/kg; and high CO{sub 2} and H{sub 2}S relative to the production wells in Palinpinon Field to the north. The chemistry of DN-1 discharge-fluid and the origin of sulphur have been the cause of apprehension for any future development due to concerns on the presence of a possible acid resource southeast of Cuernos de Negros. A reinterpretation of the previous and newmore » surface data was undertaken in 1992 and 1996, including the origin of sulphur, to evaluate the potential of Dauin for development. The results indicate that the sulphur in DN-1 is formed from partial oxidation of hydrogen sulphide derived from the neutralised-acid fluids formed by sulphur hydrolysis at shallow levels but distant from DN-1. The study argues for the presence of near neutral exploitable resource in the prospect area.« less

  14. Local Thermonuclear Runaways in Dwarf Novae?

    NASA Astrophysics Data System (ADS)

    Shara, Michael

    2012-10-01

    We have no hope of understanding the structure and evolution of a class of astrophysical objects if we cannot identify the dominant energy source of those objects.The Disk Instability Model {DIM} postulates that Dwarf Nova {DN} outbursts are powered by runaway accretion from an accretion disk onto a White Dwarf {WD} in a red dwarf-WD mass transferring binary. Ominously, HST observations {e.g. Sion et al. 2001} of WD surface abundances hint at a significant shortcoming of the DIM. The data from the present proposal will be able to unequivocally demonstrate if the observed highly Carbon-depleted and Nitrogen-enhanced abundances on WD surfaces {NOT predicted by DIM} vary with binary orbital phase, or throughout a DN quiescence cycle, or from cycle to cycle. These same data will test if predicted {but never observed} Local Thermonuclear Runaways {"Nuclear-powered mini-novas"} occur on the WDs of DN. Such events could trigger or even power DN, providing the long-sought physical mechanism of DN eruptions that DIM lacks. As a "free" bonus, the same data may also directly detect the diffusion of accreted metals in a WD atmosphere for the first time, or provide significant limits on the diffusion rate.

  15. Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants.

    PubMed

    de Jong, Jan; Skee, Donna; Murphy, Joe; Sukbuntherng, Juthamas; Hellemans, Peter; Smit, Johan; de Vries, Ronald; Jiao, Juhui James; Snoeys, Jan; Mannaert, Erik

    2015-08-01

    Ibrutinib (PCI-32765), a potent covalent inhibitor of Bruton's tyrosine kinase, has shown efficacy against a variety of B-cell malignancies. Given the prominent role of CYP3A in ibrutinib metabolism, effect of coadministration of CYP3A perpetrators with ibrutinib was evaluated in healthy adults. Ibrutinib (120 mg [Study 1, fasted], 560 mg [studies 2 (fasted), and 3 (nonfasted)]) was given alone and with ketoconazole [Study 1; 400 mg q.d.], rifampin [Study 2; 600 mg q.d.], and grapefruit juice [GFJ, Study 3]. Lower doses of ibrutinib were used together with CYP3A inhibitors [Study 1: 40 mg; Study 3: 140 mg], as safety precaution. Under fasted condition, ketoconazole increased ibrutinib dose-normalized (DN) exposure [DN-AUClast: 24-fold; DN-C max: 29-fold], rifampin decreased ibrutinib exposure [C max: 13-fold; AUClast: 10-fold]. Under nonfasted condition, GFJ caused a moderate increase [DN-C max: 3.5-fold; DN-AUC: 2.2-fold], most likely through inhibition of intestinal CYP3A. Half-life was not affected by CYP perpetrators indicating the interaction was mainly on first-pass extraction. All treatments were well-tolerated.

  16. The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

    PubMed

    Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

    2016-01-01

    Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies.

  17. The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

    PubMed Central

    Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

    2016-01-01

    Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies. PMID:27227331

  18. 29 CFR 1983.101 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) PROCEDURES FOR THE HANDLING OF RETALIATION COMPLAINTS UNDER SECTION 219 OF THE CONSUMER PRODUCT SAFETY... Consumer Product Safety Commission. (d) Complainant means the employee who filed a CPSIA complaint or on whose behalf a complaint was filed. (e)(1) Consumer product means any article, or component part thereof...

  19. 29 CFR 1983.101 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) PROCEDURES FOR THE HANDLING OF RETALIATION COMPLAINTS UNDER SECTION 219 OF THE CONSUMER PRODUCT SAFETY... Consumer Product Safety Commission. (d) Complainant means the employee who filed a CPSIA complaint or on whose behalf a complaint was filed. (e)(1) Consumer product means any article, or component part thereof...

  20. 76 FR 47610 - Certain Electronic Digital Media Devices and Components Thereof; Notice of Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ... 337 of the Tariff Act of 1930, as amended, 19 U.S.C. 1337, on behalf of Apple, Inc. of Cupertino... upon which this notice of investigation shall be served: (a) The complainant is: Apple Inc., 1 Infinite...

  1. 78 FR 23955 - Certain Toner Cartridges and Components Thereof; Commission Determination Not To Review an...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ....; Atman, Inc. d/b/a pcRUSH.com ; Dexxxon Digital Storage, Inc.; Discount Office Items, Inc. and Deal... have on (1) the public health and welfare, (2) competitive conditions in the U.S. economy, (3) U.S...

  2. 32 CFR 1633.1 - Classifying authority.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... certified him to be a member of an armed force or reserve component thereof. (b) The National Selective..., 4-A, 4-A-A, 4-B, 4-C, 4-F, 4-G, 4-T or 4-W for which he is eligible upon request by the registrant...

  3. 78 FR 24775 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-745] Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and Components Thereof; Commission Decision... importation of certain wireless communication devices, portable music and data processing devices, computers...

  4. 78 FR 12785 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-745] Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and Components Thereof; Commission Decision... importation of certain wireless communication devices, portable music and data processing devices, computers...

  5. 33 CFR 238.6 - General policy.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... system of pipes traditionally recognized as a storm drainage system. Flood damage reduction works... ditches with carrying capacities typical of storm sewer pipes. Location of political boundaries will not... the Corps of Engineers. (2) Construction of storm sewer systems and components thereof will be a non...

  6. 33 CFR 238.6 - General policy.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... system of pipes traditionally recognized as a storm drainage system. Flood damage reduction works... ditches with carrying capacities typical of storm sewer pipes. Location of political boundaries will not... the Corps of Engineers. (2) Construction of storm sewer systems and components thereof will be a non...

  7. 33 CFR 238.6 - General policy.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... system of pipes traditionally recognized as a storm drainage system. Flood damage reduction works... ditches with carrying capacities typical of storm sewer pipes. Location of political boundaries will not... the Corps of Engineers. (2) Construction of storm sewer systems and components thereof will be a non...

  8. 33 CFR 238.6 - General policy.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... system of pipes traditionally recognized as a storm drainage system. Flood damage reduction works... ditches with carrying capacities typical of storm sewer pipes. Location of political boundaries will not... the Corps of Engineers. (2) Construction of storm sewer systems and components thereof will be a non...

  9. 33 CFR 238.6 - General policy.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... system of pipes traditionally recognized as a storm drainage system. Flood damage reduction works... ditches with carrying capacities typical of storm sewer pipes. Location of political boundaries will not... the Corps of Engineers. (2) Construction of storm sewer systems and components thereof will be a non...

  10. 76 FR 38417 - In the Matter of Certain Protective Cases and Components Thereof; Notice of Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... be obtained by accessing its Internet server at http://www.usitc.gov . The public record for this... Gateway Oaks Drive 100, Sacramento, CA 95833. Hoffco Brands, Inc., d/b/a Celltronix, 4860 Ward Road, Wheat...

  11. 76 FR 75910 - Certain Inkjet Ink Supplies and Components Thereof; Final Determination of Violation; Termination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... International of Guangdong, China (``Tatrix''); and Ourway Image Co. Ltd. of Guangdong, China (``Ourway'') as... period of Presidential review (19 U.S.C. 1337(j)) shall be in the amount of 100 percent of the value of...

  12. 75 FR 7520 - Certain Refrigerators and Components Thereof; Notice of the Commission's Final Determination of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ... claim construction of the terms ``freezer compartment,'' ``disposed within the freezer compartment... questions concerning claim construction. After receiving briefing from the parties, the Commission determined to modify the ALJ's claim constructions of the terms ``freezer compartment,'' ``disposed within...

  13. 21 CFR 700.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL... Food, Drug, and Cosmetic Act. (b) The term cosmetic product means a finished cosmetic the manufacture of which has been completed. Any cosmetic product which is also a drug or device or component thereof...

  14. 21 CFR 700.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL... Food, Drug, and Cosmetic Act. (b) The term cosmetic product means a finished cosmetic the manufacture of which has been completed. Any cosmetic product which is also a drug or device or component thereof...

  15. 82 FR 57290 - Certain Memory Modules and Components Thereof Institution of Investigation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2017-12-04

    ...Notice is hereby given that a complaint was filed with the U.S. International Trade Commission on October 31, 2017, under section 337 of the Tariff Act of 1930, as amended, on behalf of Netlist, Inc. of Irvine, California. A supplement to the complaint was filed on November 21, 2017. The complaint alleges violations of section 337 based upon the importation into the United States, the sale for importation, and the sale within the United States after importation of certain memory modules and components thereof by reason of infringement of certain claims of U.S. Patent No. 9,606,907 (``the '907 patent'') and U.S. Patent No. 9,535,623 (``the '623 patent''). The complaint further alleges that an industry in the United States exists or is in the process of being established as required by the applicable Federal Statute. The complainant requests that the Commission institute an investigation and, after the investigation, issue a limited exclusion order and a cease and desist order.

  16. BDNF overexpression prevents cognitive deficit elicited by adolescent cannabis exposure and host susceptibility interaction.

    PubMed

    Segal-Gavish, Hadar; Gazit, Neta; Barhum, Yael; Ben-Zur, Tali; Taler, Michal; Hornfeld, Shay Henry; Gil-Ad, Irit; Weizman, Abraham; Slutsky, Inna; Niwa, Minae; Kamiya, Atsushi; Sawa, Akira; Offen, Daniel; Barzilay, Ran

    2017-07-01

    Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes. Here, utilizing a unique mouse model based on host (DISC1) X environment (THC administration) interaction, we aimed at studying the pathobiological basis through which THC exposure elicits psychiatric manifestations. Wild-Type and dominant-negative-DISC1 (DN-DISC1) mice were injected with THC (10 mg/kg) or vehicle for 10 days during mid-adolescence-equivalent period. Behavioral tests were conducted to assess exploratory activity (open field test, light-dark box test) and cognitive function (novel object recognition test). Electrophysiological effect of THC was evaluated using acute hippocampal slices, and hippocampal cannabinoid receptor type 1 and brain-derived neurotrophic factor (BDNF) protein levels were measured. Our results indicate that THC exposure elicits deficits in exploratory activity and recognition memory, together with reduced short-term synaptic facilitation and loss of BDNF surge in the hippocampus of DN-DISC mice, but not in wild-type mice. Over-expression of BDNF in the hippocampus of THC-treated DN-DISC1 mice prevented the impairment in recognition memory. The results of this study imply that induction of BDNF following adolescence THC exposure may serve as a homeostatic response geared to maintain proper cognitive function against exogenous insult. The BDNF surge in response to THC is perturbed in the presence of mutant DISC1, suggesting DISC1 may be a useful probe to identify biological cascades involved in the neurochemical, electrophysiological, and behavioral effects of cannabis related psychiatric manifestations. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Investigation of mechanisms of mesenchymal stem cells for treatment of diabetic nephropathy via construction of a miRNA-TF-mRNA network

    PubMed Central

    Yang, Hailing; Zhang, Xiaofei; Xin, Guangda

    2018-01-01

    Abstract Background: Recent studies have reported that mesenchymal stem cells (MSCs) exert therapeutic effects on the treatment of diabetic nephropathy (DN), but the underlying mechanisms remain unclear. Methods: A dataset GSE65561 was obtained from Gene Expression Omnibus (GEO) database, which contained four healthy control samples (group 1), four healthy controls samples co-cultured with MSCs (group 2), five DN samples (group 3) and five DN samples co-cultured with MSCs (group 4). The differentially expressed genes (DEGs) between group 3 vs. group 1 and group 4 vs. group 2 were constructed using Linear Models for Microarray (LIMMA) package package. Then, DAVID was used to analyze the functional enrichment of DEGs. Based on STRING database the protein-protein interaction (PPI) network was visualized by the Cytoscape plug-in CytoNCA. Besides, the hub miRNAs and transcription factors (TFs) regulating DEGs were predicted using Webgestalt. Results: Totally, 303 up-regulated and 88 down-regulated DEGs were shared in group 3 vs. group 1 and group 4 vs. group 2. Besides, the up-regulated DEGs were mainly enriched in ‘translation’ and ‘translational elongation’, while the down-regulated genes were only enriched in ‘protein kinase activity’. RPS27A and RPLP0 had a higher degree in the PPI network and they were regulated by EIF3M. In addition, ETF1 was predicted to be an important gene, which was regulated by miR-150, miR-134 and EIF2S1. Conclusions: RPS27A, RPLP0 and ETF1 may be potential targets for MSCs on the treatment of DN.HighlightsRPS27A and RPLP0 may be important genes in the treatment of MSCs for DN.TF EIF3M may play a key role in the treatment of MSCs for DN.MiR-150 and miR-134 may be essential microRNAs in the treatment of MSCs for DN. PMID:29532746

  18. Developmental excitatory-to-inhibitory GABA polarity switch is delayed in Ts65Dn mice, a genetic model of Down syndrome.

    PubMed

    Lysenko, Larisa V; Kim, Jeesun; Madamba, Francisco; Tyrtyshnaia, Anna A; Ruparelia, Aarti; Kleschevnikov, Alexander M

    2018-07-01

    Down syndrome (DS) is the most frequent genetic cause of developmental abnormalities leading to intellectual disability. One notable phenomenon affecting the formation of nascent neural circuits during late developmental periods is developmental switch of GABA action from depolarizing to hyperpolarizing mode. We examined properties of this switch in DS using primary cultures and acute hippocampal slices from Ts65Dn mice, a genetic model of DS. Cultures of DIV3-DIV13 Ts65Dn and control normosomic (2 N) neurons were loaded with FURA-2 AM, and GABA action was assessed using local applications. In 2 N cultures, the number of GABA-activated cells dropped from ~100% to 20% between postnatal days 3-13 (P3-P13) reflecting the switch in GABA action polarity. In Ts65Dn cultures, the timing of this switch was delayed by 2-3 days. Next, microelectrode recordings of multi-unit activity (MUA) were performed in CA3 slices during bath application of the GABA A agonist isoguvacine. MUA frequency was increased in P8-P12 and reduced in P14-P22 slices reflecting the switch of GABA action from excitatory to inhibitory mode. The timing of this switch was delayed in Ts65Dn by approximately 2 days. Finally, frequency of giant depolarizing potentials (GDPs), a form of primordial neural activity, was significantly increased in slices from Ts65Dn pups at P12 and P14. These experimental evidences show that GABA action polarity switch is delayed in Ts65Dn model of DS, and that these changes lead to a delay in maturation of nascent neural circuits. These alterations may affect properties of neural circuits in adult animals and, therefore, represent a prospective target for pharmacotherapy of cognitive impairment in DS. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Roux-en-Y Esophagojejunostomy Ameliorates Renal Function Through Reduction of Renal Inflammatory and Fibrotic Markers in Diabetic Nephropathy.

    PubMed

    Wang, Cuifang; He, Bing; Piao, Dongxu; Han, Ping

    2016-07-01

    Roux-en-Y bariatric surgery has been shown to have a remarkable and sustainable improvement in type 2 diabetes. Recent clinical studies have shown that bariatric surgery can improve or halt the development of diabetic microvascular complications such as nephropathy. However, the exact underlying mechanisms of surgical procedures are unknown. Here, we have investigated the effects of Roux-en-Y esophagojejunostomy (RYEJ) on renal function and inflammation and fibrosis biomarkers for renal injury in type 2 diabetic rats. Sprague-Dawley rats with high fat diet and streptozotocin (STZ)-induced diabetes were randomly assigned into four groups: diabetic nephropathy (DN), DN treated with food restriction (DN-FR), DN treated with RYEJ surgery (DN-RYEJ), and DN-RYEJ sham (n = 6/group). Age-matched normal rats were assigned as control group. RYEJ and sham surgeries were performed. Hyperinsulinemic-euglycemic clamps with tracer infusion were completed to assess insulin sensitivity. Twenty-four hour urine albumin excretion rate (UAER) and glomerular filtration rate (GFR) were measured. The renal pathological injury was assessed by hematoxylin and eosin (HE) staining. Kidney messenger RNA (mRNA) and/or protein content/distribution of phospho-c-Jun NH2-terminal kinase (JNK), monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, and mitogen-activated protein kinase phosphatase 5 (MKP5) were evaluated by real-time PCR and/or Western blotting/immunohistochemistry. Roux-en-Y esophagojejunostomy improved insulin sensitivity. RYEJ ameliorated renal function by improving UAER and GFR and attenuated glomerular hypertrophy after surgery. RYEJ also significantly downregulated the levels of JNK-mediated inflammatory response and upregulated the level of the anti-inflammatory mediator MKP5. Roux-en-Y esophagojejunostomy alleviates insulin resistance. RYEJ surgery ameliorated renal function and attenuated glomerular hypertrophy in a DN rat model. The considerable nephroprotective function may be mainly attributed to the reduced inflammatory and fibrotic biomarkers after RYEJ. The improvements in renal function and inflammation are not wholly dependent on the magnitude of weight loss.

  20. Reflection statistics of weakly disordered optical medium when its mean refractive index is different from an outside medium

    NASA Astrophysics Data System (ADS)

    Pradhan, Prabhakar; John Park, Daniel; Capoglu, Ilker; Subramanian, Hariharan; Damania, Dhwanil; Cherkezyan, Lusik; Taflove, Allen; Backman, Vadim

    2017-06-01

    Statistical properties of light waves reflected from a one-dimensional (1D) disordered optical medium [n(x) = n0+ dn(x), =0] have been well studied, however, most of the studies have focused on the situation when the mean refractive index of the optical medium matched with the outside medium, i.e., n0= nout=1. Further, considering dn(x) as a Gaussian color noise refractive index medium with exponential spatial correlation decay length lc and k as the incident wave vector, it has been shown that for smaller correlation length limit, i.e., klc <<1, both the mean reflection coefficient and std of r, σ(r), have same value, and they follow the relation = σ(r) ∝ lc. However, when the refractive index of the sample medium is different from the outside medium, the reflection statistics may have interesting features, which has not been well studied or understood. We studied the reflection statistics of a 1D weakly disordered optical medium with the mean background refractive index n0 being different from the outside medium nout (≠n0), to see the effect of mismatching (i.e., value of n0- nout) on the reflection statistics. In the mismatched case, the results show that the mean reflection coefficient follows a form similar to that of the matched refractive-index case, i.e., ∝ lc, with a linear increased shift, which is due to 1D uniform background reflection from a slab. However, σ(r) is shown to be σ(r) ∝ (lc)1/2, which is different from the matched case. This change in std of r is attributed to the interference between the mismatched-crerated edge mediated multiple scattering that are coupled with the random scattering. Applications to light scattering from random layered media and biological cells are discussed.

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