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2. New C3H KitN824K/WT cancer mouse model develops late-onset malignant mammary tumors with high penetrance

Author

Klein-Rodewald, T., Micklich, K., Sanz-Moreno, A., Tost, M., Calzada-Wack, J., Adler, T., Klaften, M., Sabrautzki, S., Aigner, B., Kraiger, M.J., Gailus-Durner, V., Fuchs, H., German Mouse Clinic Consortium (Aguilar-Pimentel, J.A., Becker, L., Garrett, L., Hölter, S.M., Prehn, C., Rácz, I., Rozman, J., Puk, O., Schrewe, A., Adamski, J., Esposito, I., Wurst, W., Stöger, C.), Gründer, A., Pahl, H., Wolf, E., Hrabě de Angelis, M., and Rathkolb, B.

Subjects
Multidisciplinary
Abstract

Gastro-intestinal stromal tumors and acute myeloid leukemia induced by activating stem cell factor receptor tyrosine kinase (KIT) mutations are highly malignant. Less clear is the role of KIT mutations in the context of breast cancer. Treatment success of KIT-induced cancers is still unsatisfactory because of primary or secondary resistance to therapy. Mouse models offer essential platforms for studies on molecular disease mechanisms in basic cancer research. In the course of the Munich N-ethyl-N-nitrosourea (ENU) mutagenesis program a mouse line with inherited polycythemia was established. It carries a base-pair exchange in the Kit gene leading to an amino acid exchange at position 824 in the activation loop of KIT. This KIT variant corresponds to the N822K mutation found in human cancers, which is associated with imatinib-resistance. C3H KitN824K/WT mice develop hyperplasia of interstitial cells of Cajal and retention of ingesta in the cecum. In contrast to previous Kit-mutant models, we observe a benign course of gastrointestinal pathology associated with prolonged survival. Female mutants develop mammary carcinomas at late onset and subsequent lung metastasis. The disease model complements existing oncology research platforms. It allows for addressing the role of KIT mutations in breast cancer and identifying genetic and environmental modifiers of disease progression.

Published
2022

6. Phenotypic and pathomorphological characteristics of a novel mutant mouse model for maturity-onset diabetes of the young type 2 (MODY 2)

Author

van Burck, L., Blutke, A., Kautz, S., Rathkolb, B., Klaften, M., Wagner, S., Kemter, E., de Angelis, M. Hrabe, Wolf, E., Aigner, B., Wanke, R., and Herbach, N.

Subjects
Gene mutations -- Health aspects, Gene mutations -- Research, Pancreatic beta cells -- Physiological aspects, Pancreatic beta cells -- Research, Type 2 diabetes -- Risk factors, Type 2 diabetes -- Genetic aspects, Type 2 diabetes -- Research, Biological sciences
Abstract

Several mutant mouse models for human diseases such as diabetes mellitus have been generated in the large-scale Munich ENU (N-ethyl-N-nitrosourea) mouse mutagenesis project. The aim of this study was to identify the causal mutation of one of these strains and to characterize the resulting diabetic phenotype. Mutants exhibit a T to G transversion mutation at nt 629 in the glucokinase (Gck) gene, leading to an amino acid exchange from methionine to arginine at position 210. Adult Munich [Gck.sup.M210R] mutant mice demonstrated a significant reduction of hepatic glucokinase enzyme activity but equal glucokinase mRNA and protein abundances. While homozygous mutant mice exhibited growth retardation and died soon after birth in consequence of severe hyperglycemia, heterozygous mutant mice displayed only slightly elevated blood glucose levels, present from birth, with development of disturbed glucose tolerance and glucose-induced insulin secretion. Additionally, insulin sensitivity and fasting serum insulin levels were slightly reduced in male mutant mice from an age of 90 days onward. While [beta]-cell mass was unaltered in neonate heterozygous and homozygous mutant mice, the total islet and [beta]-cell volumes and the total volume of isolated [beta]-cells were significantly decreased in 210-day-old male, but not female heterozygous mutant mice despite undetectable apoptosis. These findings indicate that reduced total islet and [beta]-cell volumes of male mutants might emerge from disturbed postnatal islet neogenesis. Considering the lack of knowledge about the pathomorphology of maturity-onset diabetes of the young type 2 (MODY 2), this glucokinase mutant model of reduced total islet and total [beta]-cell volume provides the opportunity to elucidate the impact of a defective glucokinase on development and maintenance of [beta]-cell mass and its relevance in MODY 2 patients. glucokinase; [beta]-cell; pancreas; Munich ENU mouse mutagenesis project doi:10.1152/ajpendo.00465.2009.

Published
2010

7. MICADO: Recent Developments of Models for Design and Evaluation of Electric Aircraft Propulsion Systems

Author

Aigner, B., Strathoff, P., and Stumpf, E.

Subjects
Conceptual aircraft design, ComputerApplications_COMPUTERSINOTHERSYSTEMS, Electric Propulsion, MICADO
Abstract

Deutscher Luft- und Raumfahrtkongress, DLRK, Aachen (online), Germany, 1 Sep 2020 - 3 Sep 2020; Deutsche Gesellschaft für Luft- und Raumfahrt - Lilienthal-Oberth e.V. (2021). doi:10.25967/530051, Published by Deutsche Gesellschaft für Luft- und Raumfahrt - Lilienthal-Oberth e.V.

Published
2021
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8. MICADO: Overview of Recent Developments within the Conceptual Aircraft Design and Optimization Environment

Author

Schültke, F., Aigner, B., Effing, T., Strathoff, P., and Stumpf, E.

Subjects
Conceptual aircraft design, MICADO
Abstract

This paper presents recent developments within the Multidisciplinary Integrated Conceptual Aircraft Design and Optimization environment (MICADO). MICADO has been developed at the Institute of Aerospace Systems of RWTH Aachen University since 2008; the last full status overview, however, was given in 2012. In the course of the last years, not only the underlying software architecture but also the level of detail in the different disciplines of conceptual aircraft design have been continuously improved. In the field of software architecture, the developer- and user-friendliness have increased. At the same time, improvements in methodology and modules have enabled re-designs of already existing aircraft and evaluation capabilities of different technologies. In addition, the design scope has been extended to smaller aircraft from the CS-23 sector, and the aircraft design analysis competencies have been expanded to economic, ecological, and sociological aspects. An overview of projects in which MICADO has been used shows the manifold applicability of the software.

Published
2021
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16. FEM computation of the forces on the arc of a DC-furnace

Author

Biro, O., Preis, K., Richter, K.R., Aigner, B., Schuchlenz, W.H., and Nix, E.

Subjects
Electric furnaces -- Design and construction, Magnetic fields -- Analysis, Steel, Electrical -- Magnetic properties, Finite element method -- Usage, Business, Electronics, Electronics and electrical industries
Abstract

A finite element model of a DC arc furnace is investigated in order to predict the forces acting on the arc due to the magnetic field. The currents have an a priori unknown distribution in the steel tank wall, in the anode, in the melt and in the cathode, so a current flow problem is analysed in the first step. Th current density is solved for in terms of a current vector potential whose edge element representation is used in the subsequent nonlinear magnetic field calculation to act as impressed magnetic field. The current dependence of the shielding provided by the steel tank is investigated. It is shown that by providing an asymmetrical feed of the current, the force on the arc can be reduced substantially.

Published
1994

19. Uromodulin retention in thick ascending limb of Henle's loop affects SCD1 in neighboring proximal tubule: Renal transcriptome studies in mouse models of uromodulin-associated kidney disease

Author

Horsch, M., Beckers, J., Fuchs, H., Gailus-Durner, V., Hrabě de Angelis, M., Rathkolb, B., Wolf, E., Aigner, B., and Kemter, E.

Abstract

Uromodulin-associated kidney disease (UAKD) is a hereditary progressive renal disease which can lead to renal failure and requires renal replacement therapy. UAKD belongs to the endoplasmic reticulum storage diseases due to maturation defect of mutant uromodulin and its retention in the enlarged endoplasmic reticulum in the cells of the thick ascending limb of Henle's loop (TALH). Dysfunction of TALH represents the key pathogenic mechanism of UAKD causing the clinical symptoms of this disease. However, the molecular alterations underlying UAKD are not well understood. In this study, transcriptome profiling of whole kidneys of two mouse models of UAKD, UmodA227T and UmodC93F, was performed. Genes differentially abundant in UAKD affected kidneys of both Umod mutant lines at different disease stages were identified and verified by RT-qPCR. Additionally, differential protein abundances of SCD1 and ANGPTL7 were validated by immunohistochemistry and Western blot analysis. ANGPTL7 expression was down-regulated in TALH cells of Umod mutant mice which is the site of the mutant uromodulin maturation defect. SCD1 was expressed selectively in the S3 segment of proximal tubule cells, and SCD1 abundance was increased in UAKD affected kidneys. This finding demonstrates that a cross talk between two functionally distinct tubular segments of the kidney, the TALH segment and the S3 segment of proximal tubule, exists.

Published
2014

20. Plantar Erythrodysesthesia Caused by Antiretroviral Treatment: A Case Report and Review of the Literature

Author

Aigner, B., Brockow, K., Darsow, U., Ring, J., and Plötz, S. G.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, stomatognathic diseases, Article Subject, otorhinolaryngologic diseases, skin and connective tissue diseases
Abstract

Palmoplantar erythrodysesthesia is an uncommon localised cutaneous reaction to certain chemotherapeutic agents and characterized by painful palmoplantar erythema and dysesthesia. To the best of our knowledge, we report the first case of plantar erythrodysesthesia in a 40-year-old male patient receiving an antiretroviral combination therapy for HIV.

Published
2013
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21. Educational measurement im dermatologischen e-learning: Eine Metaanalyse von 38 Studien und Literaturübersicht

Author

Aigner, B and Smolle, J

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund Seit Jahren findet e-learning im dermatologischen Bereich Anwendung. Es hat kein Institut bis jetzt eine Metaanalyse aller Studien von Beginn des e-learning bis heute durchgeführt, mit dem Fokus auf der Frage, welche Präsentationstechnik den größten Lernerfolg gewährt[for full text, please go to the a.m. URL], Evidenz und Entscheidung: System unter Druck; 10. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin

Published
2009
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23. Kutane Sarkome

Author

Aigner, B., primary, Ugurel, S., additional, Kaddu, S., additional, and Becker, J.C., additional

Published
2014
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24. Prediabetic phenotype in transgenic pigs expressing the mutant insulin C93S

Author

Braun-Reichhart, C, primary, Streckel, E, additional, Klymiuk, N, additional, Herbach, N, additional, Landbrecht-Schessl, C, additional, Wünsch, A, additional, Kessler, B, additional, Kurome, M, additional, Krebs, S, additional, Nagashima, H, additional, Blum, H, additional, Wanke, R, additional, Aigner, B, additional, Wolf, E, additional, and Renner, S, additional

Published
2014
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26. Genetic diseases and molecular genetics

Author

Legendre, C., primary, Cohen, D., additional, Delmas, Y., additional, Feldkamp, T., additional, Fouque, D., additional, Furman, R., additional, Gaber, O., additional, Greenbaum, L., additional, Goodship, T., additional, Haller, H., additional, Herthelius, M., additional, Hourmant, M., additional, Licht, C., additional, Moulin, B., additional, Sheerin, N., additional, Trivelli, A., additional, Bedrosian, C. L., additional, Loirat, C., additional, Legendre, C., additional, Babu, S., additional, Jungraithmayr, T., additional, Lebranchu, Y., additional, Riedl, M., additional, Gaber, A. O., additional, Bedrosian, C., additional, Muus, P., additional, Douglas, K., additional, Remuzzi, G., additional, Kourouklaris, A., additional, Ioannou, K., additional, Athanasiou, I., additional, Demetriou, K., additional, Panagidou, A., additional, Zavros, M., additional, Rodriguez C, N. Y., additional, Blasco, M., additional, Arcal, C., additional, Quintana, L. F., additional, Rodriguez de Cordoba, S., additional, Campistol, J. M., additional, Bachmann, N., additional, Eisenberger, T., additional, Decker, C., additional, Bolz, H. J., additional, Bergmann, C., additional, Pesce, F., additional, Cox, S. N., additional, Serino, G., additional, De Palma, G., additional, Sallustio, F. P., additional, Schena, F., additional, Falchi, M., additional, Pieri, M., additional, Stefanou, C., additional, Zaravinos, A., additional, Erguler, K., additional, Lapathitis, G., additional, Dweep, H., additional, Sticht, C., additional, Anastasiadou, N., additional, Zouvani, I., additional, Voskarides, K., additional, Gretz, N., additional, Deltas, C. C., additional, Ruiz, A., additional, Bonny, O., additional, Sallustio, F., additional, Curci, C., additional, Cox, S., additional, Kemter, E., additional, Sklenak, S., additional, Aigner, B., additional, Wanke, R., additional, Kitzler, T. M., additional, Moskowitz, J. L., additional, Piret, S. E., additional, Lhotta, K., additional, Tashman, A., additional, Velez, E., additional, Thakker, R. V., additional, Kotanko, P., additional, Leierer, J., additional, Rudnicki, M., additional, Perco, P., additional, Koppelstaetter, C., additional, Mayer, G., additional, Sa, M. J. N., additional, Alves, S., additional, Storey, H., additional, Flinter, F., additional, Willems, P. J., additional, Carvalho, F., additional, Oliveira, J., additional, Arsali, M., additional, Papazachariou, L., additional, Demosthenous, P., additional, Lazarou, A., additional, Hadjigavriel, M., additional, Stavrou, C., additional, Yioukkas, L., additional, Deltas, C., additional, Pierides, A., additional, Kkolou, M., additional, Toka, H. R., additional, Dibartolo, S., additional, Lanske, B., additional, Brown, E. M., additional, Pollak, M. R., additional, Familiari, A., additional, Zavan, B., additional, Sanna Cherchi, S., additional, Fabris, A., additional, Cristofaro, R., additional, Gambaro, G., additional, D'Angelo, A., additional, Anglani, F., additional, Toka, H., additional, Mount, D., additional, Pollak, M., additional, Curhan, G., additional, Sengoge, G., additional, Bajari, T., additional, Kupczok, A., additional, von Haeseler, A., additional, Schuster, M., additional, Pfaller, W., additional, Jennings, P., additional, Weltermann, A., additional, Blake, S., additional, Sunder-Plassmann, G., additional, Kerti, A., additional, Csohany, R., additional, Wagner, L., additional, Javorszky, E., additional, Maka, E., additional, Tulassay, T., additional, Tory, K., additional, Kingswood, J., additional, Nikolskaya, N., additional, Mbundi, J., additional, Jozwiak, S., additional, Belousova, E., additional, Frost, M., additional, Kuperman, R., additional, Bebin, M., additional, Korf, B., additional, Flamini, R., additional, Kohrman, M., additional, Sparagana, S., additional, Wu, J., additional, Brechenmacher, T., additional, Stein, K., additional, Bissler, J., additional, Franz, D., additional, Zonnenberg, B., additional, Cheung, W., additional, Wang, J., additional, Lam, D., additional, Budde, K., additional, Ivanitskiy, L., additional, Sowershaewa, E., additional, Krasnova, T., additional, Samokhodskaya, L., additional, Safarikova, M., additional, Jana, R., additional, Jitka, S., additional, Obeidova, L., additional, Kohoutova, M., additional, Tesar, V., additional, Evrengul, H., additional, Ertan, P., additional, Serdaroglu, E., additional, Yuksel, S., additional, Mir, S., additional, Yang n Ergon, E., additional, Berdeli, A., additional, Zawada, A., additional, Rogacev, K., additional, Rotter, B., additional, Winter, P., additional, Fliser, D., additional, Heine, G., additional, Bataille, S., additional, Moal, V., additional, Berland, Y., additional, Daniel, L., additional, Rosado, C., additional, Bueno, E., additional, Fraile, P., additional, Lucas, C., additional, Garcoa-Cosmes, P., additional, Tabernero, J. M., additional, Gonzalez, R., additional, Garcia-Cosmes, P., additional, Silska-Dittmar, M., additional, Zaorska, K., additional, Malke, A., additional, Musielak, A., additional, Ostalska-Nowicka, D., additional, Zachwieja, J., additional, K d r, V., additional, Uz, E., additional, Yigit, A., additional, Altuntas, A., additional, Yigit, B., additional, Inal, S., additional, Sezer, M., additional, Yilmaz, R., additional, Visciano, B., additional, Porto, C., additional, Acampora, E., additional, Russo, R., additional, Riccio, E., additional, Capuano, I., additional, Parenti, G., additional, Pisani, A., additional, Feriozzi, S., additional, Perrin, A., additional, West, M., additional, Nicholls, K., additional, Torras, J., additional, Cybulla, M., additional, Conti, M., additional, Angioi, A., additional, Floris, M., additional, Melis, P., additional, Asunis, A. M., additional, Piras, D., additional, Pani, A., additional, Warnock, D., additional, Guasch, A., additional, Thomas, C., additional, Wanner, C., additional, Campbell, R., additional, Vujkovac, B., additional, Okur, I., additional, Biberoglu, G., additional, Ezgu, F., additional, Tumer, L., additional, Hasanoglu, A., additional, Bicik, Z., additional, Akin, Y., additional, Mumcuoglu, M., additional, Ecder, T., additional, Paliouras, C., additional, Mattas, G., additional, Papagiannis, N., additional, Ntetskas, G., additional, Lamprianou, F., additional, Karvouniaris, N., additional, and Alivanis, P., additional

Published
2013
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27. Comparison of Two Sampling Methods for Assessing Halyomorpha halys (Hemiptera: Pentatomidae) Numbers in Soybean Fields.

Author

Aigner, B. L., Herbert, D. A., Dively, G. P., Venugopal, D., Whalen, J., Cissel, B., Kuhar, T. P., Brewster, C. C., Hogue, J. W., and Seymore, E.

Subjects
SOYBEAN diseases & pests, BROWN marmorated stink bug, STINKBUGS
Abstract

Sampling soybean fields for the brown marmorated stink bug, Halyomorpha halys Stål (Hemiptera: Pentatomidae), can be challenging. Both adults and nymphs have a "startle response" and drop to the ground with even the slightest disturbance. This behavior could reduce the effectiveness of the traditional sweep net and ground cloth sampling methods. In 2013 and 2014, in Virginia, Delaware, and Maryland, we evaluated a visual plant inspection method that consisted of counting the number of brown marmorated stink bug nymphs and adults seen on soybean plants in a 2-min inspection period while walking carefully between two rows. After a 30-min interval, which allowed the stink bugs to reposition in the canopy, the area was resampled using 15 sweeps with a 38-cm-diameter sweep net. In total, 76 soybean fields and 2,042 paired comparisons were used to determine a strong linear relationship between sampling methods (y = 0.984x + 0.4359, R2 = 0.6934, where y = brown marmorated stink bugs/2-min visual count and x = brown marmorated stink bugs/15 sweeps). An average visual count of 5.4 brown marmorated stink bugs in 2 min was estimated as being equivalent to the current economic threshold of 5 stink bugs per 15 sweeps. Visual inspection appears to be an effective method for assessing brown marmorated stink bug populations in soybeans. [ABSTRACT FROM AUTHOR]

Published
2016
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29. Intrinsic Josephson effects in Bi2Sr2CaCu2O8+x single crystals

Author

Aigner, B., Avenhaus, B., Kleiner, R., Kreuzer, C., Kunkel, G., Pospischil, P., Steinmeyer, F., Muller, P., and Andres, K.

Subjects
Josephson effect -- Research, Crystal detectors -- Research, Business, Electronics, Electronics and electrical industries
Abstract

The intrinsic Josephson effects in Bi2Sr2CaCu2O8+x (BSCCO) single crystals were investigated. BSCCO single crystals were grown from a stoichiometric mixture of the basic oxides and subsequently subjected to a preamplified signal at 10 gigahertz. The ouput noise power was then measured at a fixed detector frequency as a function of the voltage across the crystals. Results show that a single BSCCO crystal can function like a series array of more than 2000 Josephson junctions.

Published
1993

49. Dominant-negative effects of a novel mutated Ins2 allele causes early-onset diabetes and severe beta-cell loss in Munich Ins2C95S mutant mice.

Author

Herbach N, Rathkolb B, Kemter E, Pichl L, Klaften M, de Angelis MH, Halban PA, Wolf E, Aigner B, and Wanke R

Abstract

The novel diabetic mouse model Munich Ins2(C95S) was discovered within the Munich N-ethyl-N-nitrosourea mouse mutagenesis screen. These mice exhibit a T-->A transversion in the insulin 2 (Ins2) gene at nucleotide position 1903 in exon 3, which leads to the amino acid exchange C95S and loss of the A6-A11 intrachain disulfide bond. From 1 month of age onwards, blood glucose levels of heterozygous Munich Ins2(C95S) mutant mice were significantly increased compared with controls. The fasted and postprandial serum insulin levels of the heterozygous mutants were indistinguishable from those of wild-type littermates. However, serum insulin levels after glucose challenge, pancreatic insulin content, and homeostasis model assessment (HOMA) beta-cell indices of heterozygous mutants were significantly lower than those of wild-type littermates. The initial blood glucose decrease during an insulin tolerance test was lower and HOMA insulin resistance indices were significantly higher in mutant mice, indicating the development of insulin resistance in mutant mice. The total islet volume, the volume density of beta-cells in the islets, and the total beta-cell volume of heterozygous male mutants was significantly reduced compared with wild-type mice. Electron microscopy of the beta-cells of male mutants showed virtually no secretory insulin granules, the endoplasmic reticulum was severely enlarged, and mitochondria appeared swollen. Thus, Munich Ins2(C95S) mutant mice are considered a valuable model to study the mechanisms of beta-cell dysfunction and death during the development of diabetes. [ABSTRACT FROM AUTHOR]

Published
2007
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50. Myoclonus: Clinical Significance and an Approach to Classification

Author

AIGNER, B. ROBERT and MULDER, DONALD W.

Abstract

Myoclonus, colloquially known as "the jerks," has remained an enigmatic clinical entity for more than 70 years, despite the frequent use of this term by neurologists. During this time, little emphasis has been placed on this symptom with regard to its clinical implications and prognostic signifiicance. It is the purpose of this paper to review the records of patients exhibiting myoclonus, exclusive of patients with the rhythmic type involving the velum palatinum and the pharynx, and to report on follow-up studies on these patients. The pertinent literature will be reviewed, and the clinical and prognostic significance of myoclonus will be elaborated. DEFINITION Myoclonus may be defined as an involuntary, repetitive, desultory, instantaneous, irregular contraction of a group of muscles or, occasionally, a single muscle. Such contractions must be differentiated from the fasciculations seen clinically and in electromyographic studies. It may be difficult to recognize this clinical symptom, and the diagnosis

Published
1960
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