Academic literature on the topic 'YC 5604'

In 2013 the Editor of Journal of Vibration and Control and SAGE became aware of a peer review ring involving assumed and fabricated identities that appeared to centre around Peter Chen at National Pingtung University of Education, Taiwan (NPUE). SAGE and the Editor then began a complex investigation into the case during the rest of 2013 and 2014. Following an unsatisfactory response from Peter Chen, NPUE was notified. NPUE were serious in addressing the Journal and SAGE’s concerns. NPUE confirmed that the institution was investigating Peter Chen. SAGE subsequently uncovered a citation ring involving the above mentioned author and others. We regret that individual authors have compromised the academic record by perverting the peer review process and apologise to readers. On uncovering problems with peer review and citation SAGE immediately put steps in place to avoid similar vulnerability of the Journal to exploitation in the future. More information may be found at www.sagepub.co.uk/JVC_Statement_2014 . The Journal and SAGE understand from NPUE that Peter Chen has resigned his post at NPUE. The following articles are retracted because after thorough investigation evidence points towards them having at least one author or being reviewed by at least one reviewer who has been implicated in the peer review ring and/or citation ring. All authors have had an opportunity to respond to the allegations and proposed actions. OnlineFirst articles (these articles will not be published in an issue) Chen CY, Chen T-H, Chen Y-H, Yu S-E and Chung P-Y (2013) Information technology system modeling an integrated C-TAM-TPB model to the validation of ocean tidal analyses Journal of Vibration and Control Epub ahead of print 7 May 2013. doi: 10.1177/1077546312472924 Chang R-F, Chen CY, Su F-P and Lin H-C (2013) A two-step approach for broadband digital signal processing technique Journal of Vibration and Control Epub ahead of print 26 April 2013. doi: 10.1177/1077546312472925 Chen TH, Chang CJ, Yu SE, Chung PY and Liu C-K (2013) Nonlinear information analysis and system management technique: the influence of design experience and control complexity Journal of Vibration and Control Epub ahead of print 12 April 2013. doi: 10.1177/1077546312473321 Chen CY, Shih BY, Chen YH, Yu SE and Liu YC (2013) The exploration of a 3T flow model using vibrating NXT: II. Model validation Journal of Vibration and Control Epub ahead of print 10 April 2013. doi: 10.1177/1077546312470481 Chen CY, Shih BY, Chen YH, Yu SE and Liu YC (2013) The exploration of 3T flow model using vibrating NXT: I. model formulation Journal of Vibration and Control Epub ahead of print 6 February 2013. doi: 10.1177/1077546312467360 Lin M-L and Chen C-W (2013) Stability analysis of fuzzy-based NN modeling for ecosystems using fuzzy Lyapunov methods Journal of Vibration and Control Epub ahead of print 6 February 2013. doi: 10.1177/1077546312466687 Chen CY, Chen TH, Chen YH and Chiu J (2012) A multi-stage method for deterministic-statistical analysis: a mathematical case and measurement studies Journal of Vibration and Control Epub ahead of print 20 December 2012. doi: 10.1177/1077546312466579 Shih BY, Lin MC and Chen CY (2012) Autonomous navigation system for radiofrequency identification mobile robot e-book reader Journal of Vibration and Control Epub ahead of print 13 December 2012. doi: 10.1177/1077546312466578 Chang RF, Chen CY, Su FP, Lin HC and Lu C-K (2012) Multiphase SUMO robot based on an agile modeling-driven process for a small mobile robot Journal of Vibration and Control Epub ahead of print 13 December 2012. doi: 10.1177/1077546312464993 Shih B-Y, Lin Y-K, Cheng M-H, Chen C-Y and Chiu C-P (2012) The development of an application program interactive game-based information system Journal of Vibration and Control Epub ahead of print 12 December 2012. doi: 10.1177/1077546312464682 Chen C-Y, Chang C-J and Lin C-H (2012) On dynamic access control in web 2.0 and cloud interactive information hub: technologies Journal of Vibration and Control Epub ahead of print 12 December 2012. doi: 10.1177/1077546312464992 Shin BY, Chen CY and Hsu KH (2012) Robot cross platform system using innovative interactive theory and selection algorithms for Android application Journal of Vibration and Control Epub ahead of print 13 November 2012. doi: 10.1177/1077546312463757 Articles published in an issue Chen C-W (2014) Applications of neural-network-based fuzzy logic control to a nonlinear time-delay chaotic system Journal of Vibration and Control 20 (4): 589-605. Epub ahead of print 5 November 2012. doi: 10.1177/1077546312461370 Chen C-W (2014) A review of intelligent algorithm approaches and neural-fuzzy stability criteria for time-delay tension leg platform systems Journal of Vibration and Control 20 (4): 561-575. Epub ahead of print 5 November 2012. doi: 10.1177/1077546312463759 Chen C-Y, Chang C-J and Lin C-H (2014) On dynamic access control in web 2.0 and cloud interactive information hub: trends and theories Journal of Vibration and Control 20 (4): 548-560. Epub ahead of print 5 November 2012. doi: 10.1177/1077546312463762 Lin M-L and Chen C-W (2014) Stability conditions for ecosystem modeling using the fuzzy Lyapunov method Journal of Vibration and Control 20 (2): 290-302. Epub ahead of print 23 October 2012. doi: 10.1177/1077546312451301 Chen C-H, Kuo C-M, Hsieh S-H and Chen C-Y (2014) Highly efficient very-large-scale integration (VLSI) implementation of probabilistic neural network image interpolator Journal of Vibration and Control 20 (2): 218-224. Epub ahead of print 22 October 2012. doi: 10.1177/1077546312458822 Chen C-Y (2014) Wave vibration and simulation in dissipative media described by irregular boundary surfaces: a mathematical formulation Journal of Vibration and Control 20 (2): 191-203. Epub ahead of print 22 October 2012. doi: 10.1177/1077546312464258 Chen C-H, Yao T-K, Dai J-H and Chen C-Y (2014) A pipelined multiprocessor system- on-a-chip (SoC) design methodology for streaming signal processing Journal of Vibration and Control 20 (2): 163-178. Epub ahead of print 16 October 2012. doi: 10.1177/1077546312458821 Lin M-L and Chen C-W (2014) Fuzzy neural modeling for n-degree ecosystems using the linear matrix inequality approach Journal of Vibration and Control 20 (1): 82-93. Epub ahead of print 8 October 2012. doi: 10.1177/1077546312458533 Chen C-H, Wu W-X and Chen C-Y (2013) Ant-inspired collective problem-solving systems Journal of Vibration and Control 19 (16): 2481-2490. Epub ahead of print 18 September 2012. doi: 10.1177/1077546312456231 Chen C-H, Yao T-K, Kuo C-M and Chen C-Y (2013) Evolutionary design of constructive multilayer feedforward neural network Journal of Vibration and Control 19 (16): 2413-2420. Epub ahead of print 12 September 2012. doi: 10.1177/1077546312456726 Chen C-W (2013) Applications of the fuzzy-neural Lyapunov criterion to multiple time-delay systems Journal of Vibration and Control 19 (13): 2054-2067. Epub ahead of print 16 August 2012. doi: 10.1177/1077546312451034 Chung P-Y, Chen Y-H, Walter L and Chen C-Y (2013) Influence and dynamics of a mobile robot control on mechanical components Journal of Vibration and Control 19 (13): 1923-1935. Epub ahead of print 20 July 2012. doi: 10.1177/1077546312452184 Chen C-W (2013) Neural network-based fuzzy logic parallel distributed compensation controller for structural system Journal of Vibration and Control 19 (11): 1709-1727. Epub ahead of print 22 June 2012. doi: 10.1177/1077546312442233 Chen C-W, Yeh K, Yang H-C, Liu KFR and Liu C-C (2013) A critical review of structural system control by the large-scaled neural network linear-deferential-inclusion-based criterion Journal of Vibration and Control 19 (11): 1658-1673. Epub ahead of print 18 June 2012. doi: 10.1177/1077546312443377 Chen C-H, Kuo C-M, Chen C-Y and Dai J-H (2013) The design and synthesis using hierarchical robotic discrete-event modeling Journal of Vibration and Control 19 (11): 1603-1613. Epub ahead of print 27 June 2012. doi: 10.1177/1077546312449645 Chang CJ, Chen CY and Chou I-T (2013) The design of information and communication technologies: telecom MOD strength machines Journal of Vibration and Control 19 (10): 1499-1513. Epub ahead of print 27 June 2012. doi: 10.1177/1077546312449644 Shih B-Y, Chen C-Y, Li K-H, Wu T-Y, Chen G-Y (2013) A novel NXT control method for implementing force sensing and recycling in a training robot Journal of Vibration and Control 19 (10): 1443-1459. Epub ahead of print 1 June 2012. doi: 10.1177/1077546312446361 Chen C-W, Chen P-C and Chiang W-L (2013) Modified intelligent genetic algorithm-based adaptive neural network control for uncertain structural systems Journal of Vibration and Control 19 (9): 1333-1347. Epub ahead of print 31 May 2012. doi: 10.1177/1077546312442232 Chen C-Y, Shih B-Y, Shih C-H and Wang L-H (2013) Enhancing robust and stability control of a humanoid biped robot: system identification approach. Journal of Vibration and Control 19 (8): 1199-1207. Epub ahead of print 26 April 2012. doi: 10.1177/1077546312442947 Chang C-J, Chen C-Y and Huang C-W (2013) Applications for medical recovery using wireless control of a bluetooth ball with a hybrid G-sensor and human-computer interface technology Journal of Vibration and Control 19 (8): 1139-1151. Epub ahead of print 24 April 2012. doi: 10.1177/1077546312442948 Hsu W-K, Chiou D-J, Chen C-W, Liu M-Y, Chiang W-L and Huang P-C (2013) Sensitivity of initial damage detection for steel structures using the Hilbert-Huang transform method Journal of Vibration and Control 19 (6): 857-878. Epub ahead of print 29 February 2012. doi: 10.1177/1077546311434794 Chen C-Y, Shih B-Y, Shih C-H and Wang L-H (2013) Human–machine interface for the motion control of humanoid biped robots using a graphical user interface Motion Editor Journal of Vibration and Control 19 (6): 814-820. Epub ahead of print 23 February 2012. doi: 10.1177/1077546312437804 Chen C-Y (2013) Internal wave transport, nonlinear manifestation, and mixing in a stratified shear layer - technical briefs Journal of Vibration and Control 19 (3): 429-438. Epub ahead of print 18 January 2012. doi: 10.1177/1077546311429337 Chen C-W (2013) Delay independent criterion for multiple time-delay systems and its application in building structure control systems Journal of Vibration and Control 19 (3): 395-414. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429341 Chen C-Y, Shih B-Y, Shih C-H and Wang L-H (2013) Design, modeling and stability control for an actuated dynamic walking planar bipedal robot Journal of Vibration and Control 19 (3): 376-384. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429476 Liu K-C, Liu Y-W, Chen C-Y and Huang W-C (2013) Nonlinear vibration of structural deterioration in reinforced concrete columns: experimental and theoretical investigation Journal of Vibration and Control 19 (3): 323-335. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429477 Chen C-Y, Shih B-Y and Ma J-m (2013) Development for low-cost and cross-platform robot control environment Journal of Vibration and Control 19 (2): 228-233. Epub ahead of print 11 January 2012. doi: 10.1177/1077546311430107 Shih B-Y, Chang H and Chen C-Y (2013) Path planning for autonomous robots – a comprehensive analysis by a greedy algorithm Journal of Vibration and Control 19 (1): 130-142. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429841 Liu T-Y, Chiang W-L, Chen C-W, Hsu W-K, Lin C-W, Chiou D-J and Huang P-C (2012) Structural system identification for vibration bridges using the Hilbert–Huang transform Journal of Vibration and Control 18 (13): 1939-1956. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311428347 Chen C-W (2012) Applications of the fuzzy Lyapunov linear matrix inequality criterion to a chaotic structural system Journal of Vibration and Control 18 (13): 1925-1938. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311428346 Chen C-W (2012) Applications of linear differential inclusion-based criterion to a nonlinear chaotic system: a critical review Journal of Vibration and Control 18 (12): 1886-1899. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311428345 Shih B-Y, Chen C-Y and Chou W (2012) An enhanced obstacle avoidance and path correction mechanism for an autonomous intelligent robot with multiple sensors Journal of Vibration and Control 18 (12): 1855-1864. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311426734 Chen C-W, Yeh K, Liu KFR and Lin M-L (2012) Applications of fuzzy control to nonlinear time-delay systems using the linear matrix inequality fuzzy Lyapunov method Journal of Vibration and Control 18 (10): 1561-1574. Epub ahead of print 18 October 2011. doi: 10.1177/1077546311410765 Chen C-Y (2012) A critical review of internal wave dynamics. Part 2 – Laboratory experiments and theoretical physics Journal of Vibration and Control 18 (7): 983-1008. Epub ahead of print 21 September 2011. doi: 10.1177/1077546310397561 Chen C-Y and Huang P-H (2012) Review of an autonomous humanoid robot and its mechanical control Journal of Vibration and Control 18 (7): 973-982. Epub ahead of print 21 September 2011. doi: 10.1177/1077546310395974 Shih B-Y, Chen C-Y, Chang H and Ma J-m (2012) Dynamics and control for robotic manipulators using a greedy algorithm approach Journal of Vibration and Control 18 (6): 859-866. Epub ahead of print 25 August 2011. doi: 10.1177/1077546311407649 Yeh K, Chen C-W, Lo DC and Liu KFR (2012) Neural-network fuzzy control for chaotic tuned mass damper systems with time delays Journal of Vibration and Control 18 (6): 785-795. Epub ahead of print 15 August 2011. doi: 10.1177/1077546311407538 Chen C-Y, Shih B-Y, Shih C-H and Chou W-C (2012) The development of autonomous low-cost biped mobile surveillance robot by intelligent bricks Journal of Vibration and Control 18 (5): 577-586. Epub ahead of print 21 April 2011. doi: 10.1177/1077546310371349 Chen C-Y (2012) A critical review of internal wave dynamics. Part 1 – Remote sensing and in-situ observations Journal of Vibration and Control 18 (3): 417-436. Epub ahead of print 13 July 2011. doi: 10.1177/1077546310395971 Tseng C-P, Chen C-W and Liu KFR (2012) Risk control allocation model for pressure vessels and piping project Journal of Vibration and Control 18 (3): 385-394. Epub ahead of print 13 July 2011. doi: 10.1177/1077546311403182 Lin M-L and Chen C-W (2011) Stability analysis of community and ecosystem hierarchies using the Lyapunov method Journal of Vibration and Control 17 (13): 1930-1937. Epub ahead of print 9 December 2010. doi: 10.1177/1077546310385737 Chen C-Y, Shih B-Y, Chou W-C, Li Y-J and Chen Y-H (2011) Obstacle avoidance design for a humanoid intelligent robot with ultrasonic sensors Journal of Vibration and Control 17 (12): 1798-1804. Epub ahead of print 26 November 2010. doi: 10.1177/1077546310381101 Chen C-W (2011) Fuzzy control of interconnected structural systems using the fuzzy Lyapunov method Journal of Vibration and Control 17 (11): 1693-1702. Epub ahead of print 23 November 2010. doi: 10.1177/1077546310379625 Shih B-Y, Chen C-Y and Chou W-C (2011) Obstacle avoidance using a path correction method for autonomous control of a biped intelligent robot Journal of Vibration and Control 17 (10): 1567-1573. Epub ahead of print 22 November 2010. doi: 10.1177/1077546310372004 Tang J-P, Chiou D-J, Chen C-W, Chiang W-L, Hsu W-K, Chen C-Y and Liu T-Y (2011) A case study of damage detection in benchmark buildings using a Hilbert-Huang Transform-based method Journal of Vibration and Control 17 (4): 623-636. Epub ahead of print 8 November 2010. doi: 10.1177/1077546309360053 Liu TY, Chiang WL, Chen CW, Hsu WK, Lu LC and Chu TJ (2011) Identification and monitoring of bridge health from ambient vibration data Journal of Vibration and Control 17 (4): 589-603. Epub ahead of print 12 November 2010. doi: 10.1177/1077546309360049 Lin JW, Huang CW, Shih CH and Chen CY (2011) Fuzzy Lyapunov Stability Analysis and NN Modeling for Tension Leg Platform Systems Journal of Vibration and Control 17 (1): 151-158. Epub ahead of print 25 August 2010. doi: 10.1177/1077546309350477 Lee WI, Chen CY, Kuo HM and Sui YC (2010) The Development of Half-circle Fuzzy Numbers and Application in Fuzzy Control Journal of Vibration and Control 16 (13): 1977-1987. Epub ahead of print 22 April 2010. doi: 10.1177/1077546309349849

In 2013 the Editor of Journal of Vibration and Control and SAGE became aware of a peer review ring involving assumed and fabricated identities that appeared to centre around Peter Chen at National Pingtung University of Education, Taiwan (NPUE). SAGE and the Editor then began a complex investigation into the case during the rest of 2013 and 2014. Following an unsatisfactory response from Peter Chen, NPUE was notified. NPUE were serious in addressing the Journal and SAGE’s concerns. NPUE confirmed that the institution was investigating Peter Chen. SAGE subsequently uncovered a citation ring involving the above mentioned author and others. We regret that individual authors have compromised the academic record by perverting the peer review process and apologise to readers. On uncovering problems with peer review and citation SAGE immediately put steps in place to avoid similar vulnerability of the Journal to exploitation in the future. More information may be found at www.sagepub.co.uk/JVC_Statement_2014 . The Journal and SAGE understand from NPUE that Peter Chen has resigned his post at NPUE. The following articles are retracted because after thorough investigation evidence points towards them having at least one author or being reviewed by at least one reviewer who has been implicated in the peer review ring and/or citation ring. All authors have had an opportunity to respond to the allegations and proposed actions. OnlineFirst articles (these articles will not be published in an issue) Chen CY, Chen T-H, Chen Y-H, Yu S-E and Chung P-Y (2013) Information technology system modeling an integrated C-TAM-TPB model to the validation of ocean tidal analyses Journal of Vibration and Control Epub ahead of print 7 May 2013. doi: 10.1177/1077546312472924 Chang R-F, Chen CY, Su F-P and Lin H-C (2013) A two-step approach for broadband digital signal processing technique Journal of Vibration and Control Epub ahead of print 26 April 2013. doi: 10.1177/1077546312472925 Chen TH, Chang CJ, Yu SE, Chung PY and Liu C-K (2013) Nonlinear information analysis and system management technique: the influence of design experience and control complexity Journal of Vibration and Control Epub ahead of print 12 April 2013. doi: 10.1177/1077546312473321 Chen CY, Shih BY, Chen YH, Yu SE and Liu YC (2013) The exploration of a 3T flow model using vibrating NXT: II. Model validation Journal of Vibration and Control Epub ahead of print 10 April 2013. doi: 10.1177/1077546312470481 Chen CY, Shih BY, Chen YH, Yu SE and Liu YC (2013) The exploration of 3T flow model using vibrating NXT: I. model formulation Journal of Vibration and Control Epub ahead of print 6 February 2013. doi: 10.1177/1077546312467360 Lin M-L and Chen C-W (2013) Stability analysis of fuzzy-based NN modeling for ecosystems using fuzzy Lyapunov methods Journal of Vibration and Control Epub ahead of print 6 February 2013. doi: 10.1177/1077546312466687 Chen CY, Chen TH, Chen YH and Chiu J (2012) A multi-stage method for deterministic-statistical analysis: a mathematical case and measurement studies Journal of Vibration and Control Epub ahead of print 20 December 2012. doi: 10.1177/1077546312466579 Shih BY, Lin MC and Chen CY (2012) Autonomous navigation system for radiofrequency identification mobile robot e-book reader Journal of Vibration and Control Epub ahead of print 13 December 2012. doi: 10.1177/1077546312466578 Chang RF, Chen CY, Su FP, Lin HC and Lu C-K (2012) Multiphase SUMO robot based on an agile modeling-driven process for a small mobile robot Journal of Vibration and Control Epub ahead of print 13 December 2012. doi: 10.1177/1077546312464993 Shih B-Y, Lin Y-K, Cheng M-H, Chen C-Y and Chiu C-P (2012) The development of an application program interactive game-based information system Journal of Vibration and Control Epub ahead of print 12 December 2012. doi: 10.1177/1077546312464682 Chen C-Y, Chang C-J and Lin C-H (2012) On dynamic access control in web 2.0 and cloud interactive information hub: technologies Journal of Vibration and Control Epub ahead of print 12 December 2012. doi: 10.1177/1077546312464992 Shin BY, Chen CY and Hsu KH (2012) Robot cross platform system using innovative interactive theory and selection algorithms for Android application Journal of Vibration and Control Epub ahead of print 13 November 2012. doi: 10.1177/1077546312463757 Articles published in an issue Chen C-W (2014) Applications of neural-network-based fuzzy logic control to a nonlinear time-delay chaotic system Journal of Vibration and Control 20 (4): 589-605. Epub ahead of print 5 November 2012. doi: 10.1177/1077546312461370 Chen C-W (2014) A review of intelligent algorithm approaches and neural-fuzzy stability criteria for time-delay tension leg platform systems Journal of Vibration and Control 20 (4): 561-575. Epub ahead of print 5 November 2012. doi: 10.1177/1077546312463759 Chen C-Y, Chang C-J and Lin C-H (2014) On dynamic access control in web 2.0 and cloud interactive information hub: trends and theories Journal of Vibration and Control 20 (4): 548-560. Epub ahead of print 5 November 2012. doi: 10.1177/1077546312463762 Lin M-L and Chen C-W (2014) Stability conditions for ecosystem modeling using the fuzzy Lyapunov method Journal of Vibration and Control 20 (2): 290-302. Epub ahead of print 23 October 2012. doi: 10.1177/1077546312451301 Chen C-H, Kuo C-M, Hsieh S-H and Chen C-Y (2014) Highly efficient very-large-scale integration (VLSI) implementation of probabilistic neural network image interpolator Journal of Vibration and Control 20 (2): 218-224. Epub ahead of print 22 October 2012. doi: 10.1177/1077546312458822 Chen C-Y (2014) Wave vibration and simulation in dissipative media described by irregular boundary surfaces: a mathematical formulation Journal of Vibration and Control 20 (2): 191-203. Epub ahead of print 22 October 2012. doi: 10.1177/1077546312464258 Chen C-H, Yao T-K, Dai J-H and Chen C-Y (2014) A pipelined multiprocessor system- on-a-chip (SoC) design methodology for streaming signal processing Journal of Vibration and Control 20 (2): 163-178. Epub ahead of print 16 October 2012. doi: 10.1177/1077546312458821 Lin M-L and Chen C-W (2014) Fuzzy neural modeling for n-degree ecosystems using the linear matrix inequality approach Journal of Vibration and Control 20 (1): 82-93. Epub ahead of print 8 October 2012. doi: 10.1177/1077546312458533 Chen C-H, Wu W-X and Chen C-Y (2013) Ant-inspired collective problem-solving systems Journal of Vibration and Control 19 (16): 2481-2490. Epub ahead of print 18 September 2012. doi: 10.1177/1077546312456231 Chen C-H, Yao T-K, Kuo C-M and Chen C-Y (2013) Evolutionary design of constructive multilayer feedforward neural network Journal of Vibration and Control 19 (16): 2413-2420. Epub ahead of print 12 September 2012. doi: 10.1177/1077546312456726 Chen C-W (2013) Applications of the fuzzy-neural Lyapunov criterion to multiple time-delay systems Journal of Vibration and Control 19 (13): 2054-2067. Epub ahead of print 16 August 2012. doi: 10.1177/1077546312451034 Chung P-Y, Chen Y-H, Walter L and Chen C-Y (2013) Influence and dynamics of a mobile robot control on mechanical components Journal of Vibration and Control 19 (13): 1923-1935. Epub ahead of print 20 July 2012. doi: 10.1177/1077546312452184 Chen C-W (2013) Neural network-based fuzzy logic parallel distributed compensation controller for structural system Journal of Vibration and Control 19 (11): 1709-1727. Epub ahead of print 22 June 2012. doi: 10.1177/1077546312442233 Chen C-W, Yeh K, Yang H-C, Liu KFR and Liu C-C (2013) A critical review of structural system control by the large-scaled neural network linear-deferential-inclusion-based criterion Journal of Vibration and Control 19 (11): 1658-1673. Epub ahead of print 18 June 2012. doi: 10.1177/1077546312443377 Chen C-H, Kuo C-M, Chen C-Y and Dai J-H (2013) The design and synthesis using hierarchical robotic discrete-event modeling Journal of Vibration and Control 19 (11): 1603-1613. Epub ahead of print 27 June 2012. doi: 10.1177/1077546312449645 Chang CJ, Chen CY and Chou I-T (2013) The design of information and communication technologies: telecom MOD strength machines Journal of Vibration and Control 19 (10): 1499-1513. Epub ahead of print 27 June 2012. doi: 10.1177/1077546312449644 Shih B-Y, Chen C-Y, Li K-H, Wu T-Y, Chen G-Y (2013) A novel NXT control method for implementing force sensing and recycling in a training robot Journal of Vibration and Control 19 (10): 1443-1459. Epub ahead of print 1 June 2012. doi: 10.1177/1077546312446361 Chen C-W, Chen P-C and Chiang W-L (2013) Modified intelligent genetic algorithm-based adaptive neural network control for uncertain structural systems Journal of Vibration and Control 19 (9): 1333-1347. Epub ahead of print 31 May 2012. doi: 10.1177/1077546312442232 Chen C-Y, Shih B-Y, Shih C-H and Wang L-H (2013) Enhancing robust and stability control of a humanoid biped robot: system identification approach. Journal of Vibration and Control 19 (8): 1199-1207. Epub ahead of print 26 April 2012. doi: 10.1177/1077546312442947 Chang C-J, Chen C-Y and Huang C-W (2013) Applications for medical recovery using wireless control of a bluetooth ball with a hybrid G-sensor and human-computer interface technology Journal of Vibration and Control 19 (8): 1139-1151. Epub ahead of print 24 April 2012. doi: 10.1177/1077546312442948 Hsu W-K, Chiou D-J, Chen C-W, Liu M-Y, Chiang W-L and Huang P-C (2013) Sensitivity of initial damage detection for steel structures using the Hilbert-Huang transform method Journal of Vibration and Control 19 (6): 857-878. Epub ahead of print 29 February 2012. doi: 10.1177/1077546311434794 Chen C-Y, Shih B-Y, Shih C-H and Wang L-H (2013) Human–machine interface for the motion control of humanoid biped robots using a graphical user interface Motion Editor Journal of Vibration and Control 19 (6): 814-820. Epub ahead of print 23 February 2012. doi: 10.1177/1077546312437804 Chen C-Y (2013) Internal wave transport, nonlinear manifestation, and mixing in a stratified shear layer - technical briefs Journal of Vibration and Control 19 (3): 429-438. Epub ahead of print 18 January 2012. doi: 10.1177/1077546311429337 Chen C-W (2013) Delay independent criterion for multiple time-delay systems and its application in building structure control systems Journal of Vibration and Control 19 (3): 395-414. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429341 Chen C-Y, Shih B-Y, Shih C-H and Wang L-H (2013) Design, modeling and stability control for an actuated dynamic walking planar bipedal robot Journal of Vibration and Control 19 (3): 376-384. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429476 Liu K-C, Liu Y-W, Chen C-Y and Huang W-C (2013) Nonlinear vibration of structural deterioration in reinforced concrete columns: experimental and theoretical investigation Journal of Vibration and Control 19 (3): 323-335. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429477 Chen C-Y, Shih B-Y and Ma J-m (2013) Development for low-cost and cross-platform robot control environment Journal of Vibration and Control 19 (2): 228-233. Epub ahead of print 11 January 2012. doi: 10.1177/1077546311430107 Shih B-Y, Chang H and Chen C-Y (2013) Path planning for autonomous robots – a comprehensive analysis by a greedy algorithm Journal of Vibration and Control 19 (1): 130-142. Epub ahead of print 17 January 2012. doi: 10.1177/1077546311429841 Liu T-Y, Chiang W-L, Chen C-W, Hsu W-K, Lin C-W, Chiou D-J and Huang P-C (2012) Structural system identification for vibration bridges using the Hilbert–Huang transform Journal of Vibration and Control 18 (13): 1939-1956. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311428347 Chen C-W (2012) Applications of the fuzzy Lyapunov linear matrix inequality criterion to a chaotic structural system Journal of Vibration and Control 18 (13): 1925-1938. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311428346 Chen C-W (2012) Applications of linear differential inclusion-based criterion to a nonlinear chaotic system: a critical review Journal of Vibration and Control 18 (12): 1886-1899. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311428345 Shih B-Y, Chen C-Y and Chou W (2012) An enhanced obstacle avoidance and path correction mechanism for an autonomous intelligent robot with multiple sensors Journal of Vibration and Control 18 (12): 1855-1864. Epub ahead of print 14 December 2011. doi: 10.1177/1077546311426734 Chen C-W, Yeh K, Liu KFR and Lin M-L (2012) Applications of fuzzy control to nonlinear time-delay systems using the linear matrix inequality fuzzy Lyapunov method Journal of Vibration and Control 18 (10): 1561-1574. Epub ahead of print 18 October 2011. doi: 10.1177/1077546311410765 Chen C-Y (2012) A critical review of internal wave dynamics. Part 2 – Laboratory experiments and theoretical physics Journal of Vibration and Control 18 (7): 983-1008. Epub ahead of print 21 September 2011. doi: 10.1177/1077546310397561 Chen C-Y and Huang P-H (2012) Review of an autonomous humanoid robot and its mechanical control Journal of Vibration and Control 18 (7): 973-982. Epub ahead of print 21 September 2011. doi: 10.1177/1077546310395974 Shih B-Y, Chen C-Y, Chang H and Ma J-m (2012) Dynamics and control for robotic manipulators using a greedy algorithm approach Journal of Vibration and Control 18 (6): 859-866. Epub ahead of print 25 August 2011. doi: 10.1177/1077546311407649 Yeh K, Chen C-W, Lo DC and Liu KFR (2012) Neural-network fuzzy control for chaotic tuned mass damper systems with time delays Journal of Vibration and Control 18 (6): 785-795. 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alpha-Interferon (alpha IFN) ist derzeit die Grundlage jeder Behandlung der chronischen Hepatitis C. Zu den unerwünschten Effekten von alpha-IFN gehört die Entwicklung psychiatrischer Nebenwirkungen, die sich häufig als Depressivität äussern. Deren Häufigkeit, Schweregrad und Behandlungsbedarf wurden jedoch bisher nur unzureichend erforscht. 66 Patienten mit chronischer Hepatitis C wurden in einer Pilotstudie mit alpha-IFN als Monotherapie (3x3 MU/ Woche) oder in Kombination mit Ribavirin (1000-1200 mg/ Woche) behandelt. Sämtliche Patienten wurden vor, während und nach der Therapie hinsichtlich ihrer Depressivität beurteilt. Dies geschah sowohl im persönlichen Gespräch als auch mit Hilfe der Selbstbeurteilungsinstrumente ADS (Allgemeine Depressions Skala) und BDI (Beck Depressions Inventar). Die Ausgangsdepressivität der Hepatitispatienten entsprach dem gesunden Eichkollektiv. Im Gesamtdurchschnitt stieg die Depressivität innerhalb der ersten drei Behandlungsmonate um 5,15 (+/-8,94) Punkte auf der ADS und um 3,85 (+/-6,94) Punkte im BDI an. Weniger als ein Drittel der Patienten erlebte keine Zunahme der Depressivität. Patienten, die vor Therapiebeginn eine geringe Depressivität aufwiesen, beschrieben eine stärkere Zunahme depressiver Symptome als Patienten, die initial als depressiv beurteilt wurden. Letztere blieben während des Therapieverlaufs jedoch weiterhin depressiver als die anfangs nicht-depressiven Patienten. Vier Patienten wurden wegen schwerster depressiver Nebenwirkungen stationär psychiatrisch behandelt. Es wurde kein signifikanter Zusammenhang zwischen Ausgangsdepressivität und Behandlungserfolg festgestellt. Um stark gefährdete Patienten frühzeitig zu erkennen, wird vorgeschlagen, sowohl ADS als auch BDI vor und während der Therapie zu verwenden. Anhand eines ADS-Grenzwertes von > 17 vor und >= 30 während der Behandlung konnten 75% derjenigen Patienten, die im Verlauf der Therapie mit alpha-IFN schwerste depressive Symptome entwickelten, identifiziert werden.
Interferon-alpha (alpha-IFN) is presently the mainstay of the treatment of chronic hepatitis C. Side effects include a range of psychiatric symptoms, most frequently the development of depressive symptoms. Their incidence, severity and necessity for therapeutic intervention has not yet been sufficiently studied. 66 patients with chronic hepatitis C were enrolled in a pilot study and treated with either alpha-IFN alone (3x3 MU/ week) or in combination with Ribavirin (1000-1200 mg/ week). All patients went through repeated evaluations concerning their depressive symptoms before, during, and after treatment. Apart from individual interviews with the psychosomatic staff, the psychometric instruments used were the ADS (Allgemeine Depressions Skala, the German version of the Center for Epidemiological Studies Depression Scale, CES-D) and the BDI (Beck Depression Inventory). The initial depression score of the hepatitis C patients was comparable to that of a healthy population. On average, depression scores increased by 5,15 points (+/-8,94) on the ADS and 3,85 points (+/-6,94) on the BDI during the first 3 months of treatment. Less than a third of all patients did not show an increase of depressive symptoms. Patients with an initially low depression score experienced a greater increase of depressive symptoms than patients initially diagnosed as depressive. Nevertheless, the latter patients remained more depressive throughout the study period. Four patients developed severe depressions that necessitated admission to a psychiatric clinic. There was no significant correlation between the initial depression score and the treatment response. In order to recognize those patients at high risk for the development of severe depressions at an early stage, the author proposes the use of ADS and BDI both before and during treatment with alpha-IFN. Using a cut-off score of more than 17 points on the ADS before, and >=30 points during treatment, 75% of all patients developing severe depressions during treatment with alpha-IFN could be identified.

In Anbetracht der enormen Verbesserung der HCV-Therapie durch die Entwicklung hochwirksamer und direkt wirkender Virostatika (DAA) dient diese Studie der Analyse von HCV-Koinfektionen unter den gemeldeten HIV-Neudiagnosen in Deutschland. Zunächst wurde die Eignung zweier kommerzieller HCV Ag/Ab ELISAs, dem Murex (Abbott) und dem Monolisa (Bio-Rad), zum Nachweis von HCV in getrockneten Serumspots (DSS) verglichen. Der Murex-ELISA zeigte sich sensitiver bei Antigen-positiven Plasma-HCV-Serokonversionsproben während der Monolisa eine höhere Sensitivität bei HCV-Antikörper-positiven DSS-Eluaten. Des Weiteren wurde ein Aviditätstest zur Unterscheidung von neuen und bereits länger bestehenden Infektionen bei einem Aviditätsindex Cut-off von 40% und einem Zeitraum von 364 Tagen etabliert. Von den insgesamt 6.097 untersuchten Proben der Jahre 2015-2017 waren 396 HCV-ELISA-reaktiv (6,5%). Von diesen wurden 256 (64,6%) als aktive und 140 (35,4%) als ausgeheilte Infektionen identifiziert. Ein hoher Anteil der HCV-Koinfektionen wurde bei intra-venösen Drogenkonsumenten (77,8%, n=168/216), in der Altersgruppe der 30-39 Jährigen (9%, n=179/1.978) und bei Menschen osteuropäischer Herkunft (38,3%, n=124/324) beobachtet. Im Vergleich zum Jahr 2016 hat sich der Anteil der ausgeheilten Infektionen im Jahr 2017 bei der Gesamtzahl der Patienten (p<0,01) sowie insbesondere bei Personen ausländischer (p<0,01) und osteuropäischer (p<0,05) Herkunft erhöht. Die HCV Subtypen (St)-1a, St-3a und St-1b waren mit 33,9% (n=79/233), 33,5% (n=78/233) und 23,3% (n=52/233) vorherrschend. Der Anteil der St-1a- und St-1b-Proben, deren HCV-Sequenz gegen DAAs resistent ist, war in allen untersuchten Jahren hoch (25%-42,9%). Der beobachtete Anstieg des Anteils der ausgeheilten HCV-Koinfektionen kann auf die DAA-Therapie zurückgeführt werden. Es sind jedoch weitere Anstrengungen erforderlich, damit Gruppen mit weiterhin hoher HCV-Prävalenz von dieser Behandlung profitieren.
In light of the major shift in HCV therapy resulting from the availability of highly potent direct acting antivirals (DAA), this study performed a surveillance of HCV coinfections among reported HIV new diagnoses in Germany. First the suitability of two HCV Ag/Ab ELISAs, Murex (Abbott) and Monolisa (Bio-Rad) for dried serum spots (DSS) was compared. The Murex was more sensitive in antigen positive plasma HCV seroconversion samples while the Monolisa showed a higher sensitivity in HCV antibody positive DSS eluates. Furthermore, an avidity test was established to distinguish between new and already longer existing infections at an avidity index cut-off of 40% and a period of 364 days. Of the total of 6,097 samples examined for the years 2015-2017, 396 were HCV ELISA reactive (6.5%). Of these, 256 (64.6%) were identified as active and 140 (35.4%) as resolved infections. A high proportion of HCV coinfections were observed in intravenous drug users (77.8%, n=168/216), in the age group 30-39 years (9%, n=179/1,978) and in people of Eastern European origin (38.3%, n=124/324). Compared to 2016, the proportion of resolved infections in 2017 has increased in the total number of patients (p<0.01) and especially in people of foreign (p<0.01) and Eastern European (p<0.05) origin. HCV subtypes (St)-1a, St-3a, and St-1b were predominant with 33.9% (n=79/233), 33.5% (n=78/233) and 23.3% (n=52/233), respectively. The proportion of St-1a and St-1b samples whose HCV sequence has resistance to DAAs was high in all diagnoses years (25%-42.9%). The observed increase in the proportion of resolved HCV coinfections can be attributed to DAA therapy. However, further efforts are needed to ensure that groups with continued high HCV prevalence benefit from this treatment.

Für den Zusammenbau des HBV-Partikels ist die Interaktion zwischen Oberflächenproteinen und dem Nukleokapsid notwendig. Sich überlappende synthetische Peptide aus dem Bereich der HBcAg-Bindungsdomäne im C-Terminus der PreS1-Region und dem TLM, sind nach Internalisierung vor allem im Kern lokalisiert. Die Aminosäuren 101-115 der PreS1-Region interagieren mit dem Nukleokapsid, während die PreS2-Domäne keine Interaktion mit dem Nukleokapsid eingeht. Mit den synthetischen Peptiden konnte Einfluss auf die Sekretion viraler Partikel genommen werden. Die Lokalisation von HBcAg als Interaktionspartner in HBV-produzierenden Zellen verändert sich bei Inkubation mit den synthetischen Peptiden, es tritt vermehrt im Kern auf. Rekombinante Proteine ähnlich den synthetischen Peptiden aber mit der vollständigen PreS2-Region, sind nach Internalisierung im Zytosol nachweisbar. Die Sekretion viraler Partikel wurde partiell inhibiert. Das HBV-Genom kodiert zwei virale Aktivatoren, das HBx und die PreS2-Region im LHBs. Beide aktivieren den c-Raf-1/MEK-Signalweg. Durch die selektive Inhibierung der Effektoren (Ras oder Proteinkinase C) von HBx oder PreS2 im LHBs konnte kein Effekt auf die Genexpression/ Sekretion nachgewiesen werden. Durch simultane Inhibierung der Signalkaskade so kommt die Virussekretion fast vollständig zum Erliegen. Die Ursache hierfür ist in einer reduzierten Neusynthese von viralen Proteinen zu finden und nicht in der Akkumulation der Proteine in der Zelle. Zur Untersuchung des Einflusses der Funktionalität der beiden Aktivatoren wurden HBx- bzw. PreS2- und HBx/PreS2-defiziente HBV-Expressionsplasmide generiert. Die Einzelmutanten zeigten nur einen geringen reduzierenden Einfluss auf die Genexpression/Virussekretion. Beim Einsatz der Doppelmutante wurde die Genexpression/Virussekretion fast vollständig inhibiert. HBx und PreS2 im LHBs sind für die Virusreplikation von Bedeutung aber sie können einander ersetzen.
Assembly of HBV particles and subsequent secretion of mature virus requires the interaction of the nucleocapsid with defined domains of the surface proteins. Overlapping synthetic peptides covering the C-terminal part of the PreS1 domain and the cell permeable domain of PreS2 (TLM) were shown to localize most of all in the nucleus. Based on these peptides aa 101-115 of PreS1 were found to be essential for the interaction with the nucleocapsid, while the PreS2 domain does not interact with the nucleus. Presence of the peptides that compete the nucleocapsid surface protein interaction a block of HBV and antigen secretion was achieved. HBcAg as natural interaction partner of the surface proteins then arises increased in the nucleus. Recombinant proteins similar to the synthetic peptides but with the whole PreS2 domain localize in the cytoplasm and block HBV and antigen secretion. The genome of HBV encodes two transcriptional activators: the HBx protein and the PreS2 activator LHBs. Both trigger activation of c-Raf-1/MEK kinase cascade. To evaluate the importance of both activators for viral replication selective inhibitions of signal transduction cascades were performed and do not result in a decrease of viral replication. Simultaneous inhibition of both activators abolished viral secretion. It is due to a reduced de novo synthesis and not to an accumulation of viral proteins in cells. The relevance of activator function was tested by mutated HBV genome defective for HBx and / or PreS2 activator function. After transfection single mutants show no significant reduced HBV expression whereas at the double mutated HBV genome a strong reduced virus expression could be observed. The HBx protein and the PreS2 activator LHBs are important for viral replication but they can replace each other.

Kohlenhydrat-bindende Module (CBMs) sind die bekanntesten nicht-katalytischen Module, die mit Enzymen assoziiert sind, welche die pflanzliche Zellwand hydrolysieren. Die beta-Mannanase 26 von Caldicellulosiruptor saccharolyticus, Stamm Rt8B.4, ist eine thermostabile modulare Glycosidhydrolase, die N-terminal zwei dicht aufeinander folgende nicht-katalytische kohlenhydratbindende Module besitzt. Diese spezifisch beta-Mannan bindenden CBMs wurden kürzlich als Mitglieder der CBM-Familie 27 klassifiziert. Im ersten Teil dieser Arbeit wird die Kristallisation und Strukturanalyse des ersten kohlenhydratbindenden Moduls der ß-Mannanase aus C. saccharolyticus (CsCBM27-1) mit einer gebundenen Mannohexaose und in ligandfreier Form beschrieben. Grundlage für diese Arbeit waren Daten aus der isothermen Titrationskalorimetrie zur Quantifizierung der Affinität von CsCBM27-1 für lösliche Mannooligosaccharide. Die hier präsentierte hochaufgelöste Kristallstruktur des ungebundenen und Mannohexaose gebundenen CsCBM27-1 erlaubt weitere Einblicke in die Interaktion ß-Mannan bindender CBMs mit ihren entsprechenden Liganden. CsCBM27-1 zeigt eine typische ß-sandwich jellyroll-Struktur mit gebundenen Kalziumion. Die Mannohexaosebindung wird durch drei dem Lösungsmittel zugängliche Tryptophanreste und einige direkte Wasserstoffbrückenbindungen vermittelt. Der zweite Teil der Arbeit beschäftigt sich mit der Reinigung und Kristallisation der ATPase Virb11 HP0525 aus Helicobacter pylori. Das native Protein HP0525 ließ sich gut rekombinant herstellen und reinigen. Es wurde aus einer von mehreren Kristallisationsbedingungen durch Optimierung der Kristallisationskomponenten ausreichend große Kristalle erhalten, die gute Diffraktionseigenschaften zeigten. Neben dem nativen Protein wurde Selenomethionin-substituiertes Protein synthetisiert und gereinigt. Von diesem Protein SeMet-HP0525, resultierten hexagonale Kristalle. Zur Derivat-Datensatzsammlung ist es aufgrund der Publikation der Kristallstruktur dieser hexameren ATPase HP0525 nicht mehr gekommen. Weitere strukturelle Untersuchungen an diesem Protein wurden als nicht mehr erforderlich angesehen.
Carbohydrate-binding modules (CBMs) are the most common non-catalytic modules associated with enzymes active in plant cell-wall hydrolysis. Caldicellulosiruptor saccharolyticus strain Rt8B.4 Man26 is a thermostable modular glycoside hydrolase beta-mannanase which contains two non-catalytic modules in tandem at its N-terminus. These modules were recently shown to function primarily as ß-mannan-binding modules and have accordingly been classified as members of a novel family of CBMs, family 27. In the first part of this study, the crystallization and crystal structure analysis of the first carbohydrate binding module (CsCBM27-1) of the beta-mannanase from C. saccharolyticus in native and mannohexaose-bound form is described. The basis for this study were data from isothermal titration calorimetry for quantifying the binding affinity of CsCBM27-1 for soluble mannooligosaccharidesBoth structures permit further insights into the interaction of beta-mannan binding CBMs with their corresponding ligands. CsCBM27-1 shows the typical beta-sandwich jellyroll fold observed in other CBMs with a single calcium ion bound opposite to the ligand binding site. This arrangement is similar to topologies of other CBM families. The crystal structures reveal that the overall fold of CsCBM27-1 remains virtually unchanged upon sugar binding and that binding is mediated by three solvent-exposed tryptophan residues and few direct hydrogen bonds. The second part of this study addressed the purification and crystallization of the VirB11 ATPase HP0525 of Helicobacter pylori. The native HP0525 protein was produced in recombinant Escherichia coli and purified for crystallization. One of several crystallization experiments yielded large crystals by optimization of the concentration of the crystallization components. The crystals revealed good diffraction behavior. In addition to the native protein, selenomethionine-substituted HP0525 was produced and purified. Hexagonal crystals were obtained from the SeMet-HP0525. No derivative datasets were collected, because the crystal structure of the hexameric ATPase HP0525 was published by Yeo et al. (2000). Further structural investigations for the protein HP0525 were judged unnecessary.

Bei 22 Patienten mit Leberzirrhose wurde prospektiv der Ernährungszustand mit seinen Komponenten Energieverbrauch, Nahrungsaufnahme und Körperzusammensetzung sowohl vor Anlage eines TIPS, als auch 1, 6 und 12 Monate nach TIPS-Implantation untersucht und in Beziehung zu Daten gesunder Probanden gesetzt. Im Vergleich zu gesunden Kontrollpersonen waren bei Patienten vor TIPS-Anlage Körpergewicht und body-mass-index nicht vermindert, während Muskel- und Körperzellmasse (BCM) reduziert waren. Im Grundumsatz (REE) bestand kein Unterschied zu Kontrollen, wenn der gesamte Grundumsatz betrachtet wird. Dagegen war der spezifische, auf die Körperzellmasse bezogene Grundumsatz (REE/BCM) bei Patienten signifikant erhöht. Patienten wiesen also gegenüber Kontrollen einen hypermetabolen Status auf. Die Substratoxidation der Patienten war durch eine bevorzugte Verwendung von Lipiden gekennzeichnet. Nach TIPS-Anlage nahmen Körpergewicht und BMI der Patienten zu aufgrund einer Verbesserung in der Körperzusammensetzung mit signifikantem Anstieg von Muskelmasse, Körperzellmasse und dem Quotienten von Körperzellmasse und Körpermasse. Darüberhinaus war eine signifikante Abnahme der Aszitesmenge zu verzeichnen. Die Fettmasse blieb trotz Zunahme der Körpermasse unverändert. Entsprechend der Zunahme der Körpermasse stieg der Grundumsatz nach TIPS-Anlage signifikant an, die Betrachtung des spezifischen Energieumsatzes zeigte jedoch eine abnehmende Tendenz im Sinne einer Normalisierung des bei Zirrhosepatienten gegenüber Kontrollen erhöhten Energieumsatzes. Dieser Abnahme des spezifischen Energieverbrauchs stand eine zunehmende Nährstoffaufnahme gegenüber, so daß diese Verbesserung der Energiebilanz als eine der Ursachen für die Verbesserung des Ernährungzustandes zu sehen ist. Unbeeinflußt von der TIPS-Anlage blieb die Bevorzugung von Fett als oxidativem Substrat. Bezüglich der Organfunktionen war nach TIPS-Anlage eine partielle Verminderung der hepatischen Syntheseleistung (Quick, nicht aber Albumin) und eine signifikante Verbesserung der Nierenfunktion und psychometrisch gemessenen hirnorganischen Leistungsfähigkeit zu beobachten. Die Anlage und Funktionserhaltung eines TIPS war bei Patienten mit Leberzirrhose mit einer bedeutsamen Verbesserung des Ernährungszustandes und insbesondere des prognostisch relevanten Kompartiments Körperzellmasse und Muskelmasse verbunden. Bei unveränderten Ernährungsempfehlungen waren die Patienten in höherem Maße in der Lage, diese Empfehlungen zu realisieren und insbesondere eine höhere Eiweißmenge ohne Verschlechterung der Enzephalopathie zuzuführen. Welchen Einfluß die einzelnen Faktoren wie verminderte Aszitesmenge, Verbesserung der intestinalen Absorption oder Vermeidung erneuter kataboler Situationen (gastrointestinale Blutungen, Parazentese und Endotoxinämie durch Reduktion der portalen Hypertension) an diesem Ergebnis haben, muß durch weitere Untersuchungen geklärt werden.
22 patients with liver cirrhosis were examined prospectively regarding their nutritional state and its components energy expenditure, energy intake and body composition before and 1, 6 and 12 months after implantation of a transjugular intrahepatic portosystemic stent - shunt (TIPS). These data were compared to those corresponding of a group of healthy control subjects. Compared to these healthy individuals body weigth and body mass index (BMI) of the patients were not reduced while muscle mass and body cell mass (BCM) were impaired before TIPS-implantation. There was no difference in resting energy expenditure (REE) between both groups. The ratio REE/BCM is called specific resting energy expenditure. This ratio was found to be increased in the patient group which means that patients were hypermetabolic when compared to controls. Lipids turned out to be the prefered fuel in patients. After TIPS-insertion body weight and BMI increased in patients because muscle mass, BCM and BCM/body weight all increased significantly in the patient group. Meanwhile the amount of ascites was reduced significantly. Fat mass remained stable after TIPS. Because of this increase of body weight energy expenditure had to increase, too. On the contrary, the specific REE showed a decrease which means normalization of the pathological high results of this parameter. A decrease in specific REE and an increase in energiy intake lead to an improvement of energy balance. This is probably one min cause of the improvement in the nutritional state of the patients after TIPS. After TIPS lipids remained to be the main source of substrate for oxidation. Partly, the synthetical function of the liver was impaired after TIPS (thromboplastin time, but not Albumin) while renal function and mental performance measured by psychometric tests improved significantly. The implantation of TIPS and surveillance of its function in patients with liver cirrhosis was accompanied by an improvement of their nutritional state. Even more important, there was an improvement of body cell mass and of muscle mass which both are of significantly prognostic value in this kind of patients. Dietary recommendations were not changed after TIPS but patients were able to realize them in a better way and they tolerated an increased intake of protein without an increase in the rate of hepatic encephalopathy. Furthe studies will have to be performed in order to find out the influences of different factors as reduced amount of ascites, improvement of intestinal absorption or avoiding of catabolic periods (gastrointestinal bleeding, paracentesis and endotoxinaemia by reduction of portal hypertension).

Die vorliegende Habilitationsschrift befasst sich schwerpunktmäßig vor allem mit der Klinik und Therapie der Hepatitis C. Evaluiert wurden: 1. verschiedene therapeutische Strategien, 2. die Ursachen der "Non-Response" auf eine anti-virale Therapie sowie 3. die klinische Relevanz der neu entdeckten Hepatitis-assoziierten Viren und 4. ihre Bedeutung bei Patienten mit akuter bzw. chronischer Lebererkrankung unklarer Ätiologie sowie bei Patienten vor und nach Lebertransplantation. Ad 1. Aus dem Vergleich verschiedener Therapie-Konzepte wie der Kurzzeit- Kombinationstherapie, Triple-Therapie, Hochdosis-Interferon?-Therapie und der Anwendung antiviraler Substanzen wie Ribavirin und Amantadin ergaben sich neue Erkenntnisse hinsichtlich relevanter prognostischer Parameter für die Therapieresponse. Ad 2. Analysiert wurden die möglichen molekularen Mechanismen der Therapieresponse bzw. Non-Response sowie der Stellenwert von Interaktionen bestimmter HCV-Proteine (NS5A, E2, sogenannte PKR-eIF2a Phosphorylisations-Homologie-Domäne [PePHD]) mit den Interferon? induzierten Effektorproteinen. Es konnte gezeigt werden, daß die Anzahl der Mutationen innerhalb des NS5A Proteins einen prognostischen Parameter darstellen hinsichtlich der Response auf eine Interferon?-Therapie. Dagegen spielen Mutationen innerhalb der PePHD-Region keine Rolle. Ad 3. Aus den Untersuchungen zur klinischen Relevanz der neu entdeckten Hepatitis-assoziierten Viren GB Virus-C/Hepatitis G Virus (GBV-C/HGV) und TT-Virus (TTV) ergaben sich keine Hinweise bzgl. eines Einflusses von GBV-C/HGV bzw. TTV-Infektionen auf den Verlauf der chronischen Hepatitis C. Die durchgeführten Verlaufsuntersuchungen bei koinfizierten Patienten sprechen dafür, daß es sich um Interferon-sensitive Viren handelt; jedenfalls beeinflussen sie nicht die IFN?-induzierte Response. Ad 4. Untersucht wurden ferner die Prävalenz, Transmission und Relevanz der GBV-C/HGV und TTV-Infektion im Hinblick auf ihre Hepatitis-induzierenden Eigenschaften. Die Ergebnisse belegen, dass beide Viren parenteral übertragen werden, und dass sie eine hohe Prävalenz bei Patienten mit parenteralen Risikofaktoren besitzen. Eine Hepatitis-induzierende Potenz dieser Viren konnten wir nicht beobachten; bei der Mehrzahl aller chronisch infizierter Personen ließen sich keine Zeichen einer chronischen Hepatitis finden.
The major goal of this thesis is the analysis of the clinical outcome of patients with Hepatitis C virus (HCV) infection and the response to therapy. Analysed were 1. different types of therapeutic strategies 2. causes responsible for ineffective antiviral therapy (non-response) 3. clinical relevance of the newly discovered hepatitis-associated viruses and 4. the role of these viruses in patients with acute or chronic hepatitis of unknown causes and in those receiving liver grafts. Ad 1. Compared were different therapeutic concepts such as short-term combination therapy, triple-therapy, high dose IFN?-therapy and the use of antiviral substances such as ribavirin and amantadine. It emerged that relevant prognostic parameters can be deduced with respect to the therapeutic response rate. Ad 2. Analysed were possible molecular mechanisms, which may interfere with response or non-response to antiviral therapy. In this respect, we focussed on the interaction of certain HCV-proteins as NS5A, E2, so-called PKR-eIF2a phosphorylisation-homology-domain (PePHD). with the interferon-?-induced effector proteins. There is evidence, that number of mutations within the NS5A proteins are of prognostic relevance with respect to the response to interferon?-therapy. In contrast, mutations within the PePHD-region do not play any role in this respect. Ad 3. We also studied the clinical relevance of the newly discovered viruses GBV-C/HGV and TTV, and found, that they have no impact concerning the course of chronic hepatitis C. These viruses are interferon-sensitive and do not influence the IFNa-response as it could be documented by following the course of co-infected patients. Ad 4. Our studies also focused on the prevalence, transmission and relevance of GBV-C/HGV and TTV infections with respect to their role as hepatitis-inducing agents. We can show that both virus types are parenterally transmitted. There is a high prevalence for both types in patients confronted with risk factors for parenteral factors. From analysis of many patients being chronically infected with these viruses it became quite clear that they lack any important potency to provoke chronic liver disease.