TY - JOUR A1 - Almajhdi, Fahad N. A1 - Senger, Tilo A1 - Amer, Haitham M. A1 - Gissmann, Lutz A1 - Öhlschläger, Peter T1 - Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (Shuffling) JF - PLOS one N2 - Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0113461 SN - 1932-6203 VL - 11 IS - 9 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Alnemer, Momin Sami Mohammad A1 - Kotliar, Konstantin A1 - Neuhaus, Valentin A1 - Pape, Hans-Christoph A1 - Ciritsis, Bernhard D. T1 - Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model JF - Cost Effectiveness and Resource Allocation N2 - Background Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices. Methods This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare & Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results. Results With a 10% fracture risk reduction, model A costs between $8,850 and $46,940 per quality-adjusted life-year ($/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side’s prophylaxis, the patient’s age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between $11,000/QALY and $74,000/QALY, which is below the defined willingness to pay threshold. Conclusion Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks. KW - Hip fractures KW - Prevention KW - Geriatric KW - Cost-effectiveness KW - Prophylaxis Y1 - 2023 U6 - https://doi.org/10.1186/s12962-023-00482-4 SN - 1478-7547 N1 - Corresponding author: Momin S. Alnemer IS - 21, Article number: 77 PB - Springer Nature ER - TY - CHAP A1 - Alt, Helmut T1 - Energiewirtschaftliche Bedeutung der Windenergie T2 - Fortschrittliche Energiewandlung und -anwendung 2003 : Tagung Stuttgart, 11. und 12. März 2003. (VDI-Berichte ; 1746) Y1 - 2003 SN - 3-18-091746-6 SP - 447 EP - 459 ER - TY - CHAP A1 - Alt, Helmut T1 - Stand der Durchleitungspraxis auf Basis des neuen Energiewirtschaftsgesetzes T2 - Energie und Umwelt 2000 : Fachkongreß und Ausstellung mit DBU-Statuskolloquium der Deutschen Bundesstiftung Umwelt: In situ-Bodenreaktor-Technologie, 29. bis 30. März 2000 in Freiberg, Clemens-Winkler-Bau ; Tagungsband Y1 - 2000 SP - 86 EP - 88 ER - TY - THES A1 - Alt, Helmut T1 - Beitrag zur Spannungs-Blindleistungsregelung mit gesteuerten Netzkennlinien Y1 - 1975 N1 - Aachen, Techn. Hochsch., Diss., 1975 CY - Aachen ER - TY - JOUR A1 - Alt, Helmut T1 - Spannungs-Blindleistungs-Regelung mit gesteuerten Netzkennlinien JF - Elektrotechnische Zeitschrift : Ausgabe A, Zeitschrift für elektrische Energietechnik : ETZ Y1 - 1976 SN - 0302-265x VL - 97 IS - 7 SP - 441 EP - 446 PB - VDE-Verlag CY - Wuppertal ER - TY - JOUR A1 - Alt, Helmut T1 - Sechsunddreißig Spielarten der Verrechung : die Behandlung von Tilgungs- und Zinszahlungen JF - Frankfurter Zeitung : Blick durch die Wirtschaft : Zeitung für Finanzen, Steuern, Recht und Management Y1 - 1989 SP - vom 12.9.1989 ER - TY - CHAP A1 - Alt, Helmut T1 - Energiewirtschaftliche Bedeutung der Windenergie im Stromerzeugungsmix T2 - Innovationen für Menschen : VDE-Kongress 2004, 18. - 20. Oktober 2004 in Berlin ; Bd. 1: Fachtagungsberichte der ITG - ETG Y1 - 2004 SP - 551 EP - 559 PB - VDE-Verl. CY - Berlin [u.a.] ER - TY - JOUR A1 - Alt, Helmut T1 - Energie: Der harte Wettbewerb erfordert eine günstige Strombeschaffung - Billiger Atomstrom wird aus dem Ausland importiert - Der Strommix im Netz lässt sich nicht nach der Herkunft trennen "Grüner" Strom - ein Etikettenschwindel JF - VDI-Nachrichten vom 15.6.2001 Y1 - 2001 SP - 13 ER - TY - JOUR A1 - Alt, Helmut T1 - Leser: Es wurde nichts verschenkt JF - Handelsblatt : Deutschlands Wirtschafts- und Finanzzeitung vom 5.1.2007 Y1 - 2007 SP - 18 ER -