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6. Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial

Author

Hovorka, R, Acerini, C L, Thankamony, A, Allen, J M, Boughton, C K, Dovc, K, Dunger, D B, Ware, J, Musolino, G, Tauschmann, M, Wilinska, M E, Hayes, J F, Hartnell, S, Slegtenhorst, S, Ruan, Y, Haydock, M, Mangat, J, Denvir, L, Kanthagnany, SK, Law, J, Randell, T, Sachdev, P, Saxton, M, Coupe, A, Stafford, S, Ball, A, Keeton, R, Cresswell, R, Crate, L, Cripps, H, Fazackerley, H, Looby, L, Navarra, H, Saddington, C, Smith, V, Verhoeven, V, Bratt, S, Khan, N, Moyes, L, Sandhu, K, West, C, Wadwa, R P, Alonso, G, Forlenza, G, Slover, R, Towers, L, Berget, C, Coakley, A, Escobar, E, Jost, E, Lange, S, Messer, L, Thivener, K, Campbell, F M, Yong, J, Metcalfe, E, Allen, M, Ambler, S, Waheed, S, Exall, J, Tulip, J, Buckingham, B A, Ekhlaspour, L, Maahs, D, Norlander, L, Jacobson, T, Twon, M, Weir, C, Leverenz, B, Keller, J, Davis, N, Kumaran, A, Trevelyan, N, Dewar, H, Price, G, Crouch, G, Ensom, R, Haskell, L, Lueddeke, LM, Mauras, N, Benson, M, Bird, K, Englert, K, Permuy, J, Ponthieux, K, Marrero-Hernandez, J, DiMeglio, L A, Ismail, H, Jolivette, H, Sanchez, J, Woerner, S, Kirchner, M, Mullen, M, Tebbe, M, Besser, R EJ, Basu, S, London, R, Makaya, T, Ryan, F, Megson, C, Bowen-Morris, J, Haest, J, Law, R, Stamford, I, Ghatak, A, Deakin, M, Phelan, K, Thornborough, K, Shakeshaft, J, Weinzimer, S A, Cengiz, E, Sherr, J L, Van Name, M, Weyman, K, Carria, L, Steffen, A, Zgorski, M, Sibayan, J, Beck, R W, Borgman, S, Davis, J, Rusnak, J, Hellman, A, Cheng, P, Kanapka, L, Kollman, C, McCarthy, C, Chalasani, S, Hood, K K, Hanes, S, Viana, J, Lanning, M, Fox, D S, Arreaza-Rubin, G, Eggerman, T, Green, N, Janicek, R, Gabrielson, D, Belle, S H, Castle, J, Green, J, Legault, L, Willi, S M, Wysham, C, Ware, Julia, Boughton, Charlotte K, Allen, Janet M, Wilinska, Malgorzata E, Tauschmann, Martin, Denvir, Louise, Thankamony, Ajay, Campbell, Fiona M, Wadwa, R Paul, Buckingham, Bruce A, Davis, Nikki, DiMeglio, Linda A, Mauras, Nelly, Besser, Rachel E J, Ghatak, Atrayee, Weinzimer, Stuart A, Hood, Korey K, Fox, D Steven, Kanapka, Lauren, Kollman, Craig, Sibayan, Judy, Beck, Roy W, and Hovorka, Roman

Published
2022
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8. The immune microenvironment in EGFR- and ERBB2-mutated lung adenocarcinoma

Author

Kirchner, M., Kluck, K., Brandt, R., Volckmar, A.-L., Penzel, R., Kazdal, D., Endris, V., Neumann, O., Seker-Cin, H., Goldschmid, H., Glade, J., Allgäuer, M., Kriegsmann, M., Winter, H., Muley, T., Perner, S., Frost, N., Reck, M., Fröhling, S., Schirmacher, P., Thomas, M., Budczies, J., Christopoulos, P., and Stenzinger, A.

Published
2021
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11. Technische Zusammenfassung

Author

Jandl, R., Tappeiner, U., Foldal, C., Erb, K., Erb, K.-H., Anderl, M., Baumgarten, A., Bohner, A., Borsky, S., Bruckman, V., Bruckner, M., Díaz-Pinés, E., Dobernig, K., Dumke, H., Eitzinger, J., Fischer, T., Formayer, H., Freudenschuss, A., Gaube, V., Getzner, M., Gingrich, S., Glatzel, S., Gratzer, G., Haas, W., Jäger, J., Kirchner, M., Kitzler, B., Koch, A., Kottusch, C., Kraxner, F., Lapin, K., Leitinger, G., Lexer, M., Lindenthal, T., Loibl, W., Mehdi-Schulz, B., Meyer, I., Miloczki, J., Obrovsky, M., Penker, M., Sandén, T., Scharler, M., Schauberger, G., Mag. Dr. MSc. Schaumberger, A., Schinko, T., Shinozaki, K., Schirpke, U., Schmid, C., Schneider, S., Schöner, W., Schüler, S., Sinabell, F., Spiegel, H., Stöglehner, G., Stumpp, C., Sturmbauer, C., Tasser, E., Thaler, T., Theurl, M., Tötzer, T., Voigt, A., Weber, K., Weber, G., Weiss, P., Wenzel, W., Zessner, M., Zoboli, O., Zollitsch, W., Zuvela-Aloise, M., Jandl, R., Tappeiner, U., Foldal, C., Erb, K., Erb, K.-H., Anderl, M., Baumgarten, A., Bohner, A., Borsky, S., Bruckman, V., Bruckner, M., Díaz-Pinés, E., Dobernig, K., Dumke, H., Eitzinger, J., Fischer, T., Formayer, H., Freudenschuss, A., Gaube, V., Getzner, M., Gingrich, S., Glatzel, S., Gratzer, G., Haas, W., Jäger, J., Kirchner, M., Kitzler, B., Koch, A., Kottusch, C., Kraxner, F., Lapin, K., Leitinger, G., Lexer, M., Lindenthal, T., Loibl, W., Mehdi-Schulz, B., Meyer, I., Miloczki, J., Obrovsky, M., Penker, M., Sandén, T., Scharler, M., Schauberger, G., Mag. Dr. MSc. Schaumberger, A., Schinko, T., Shinozaki, K., Schirpke, U., Schmid, C., Schneider, S., Schöner, W., Schüler, S., Sinabell, F., Spiegel, H., Stöglehner, G., Stumpp, C., Sturmbauer, C., Tasser, E., Thaler, T., Theurl, M., Tötzer, T., Voigt, A., Weber, K., Weber, G., Weiss, P., Wenzel, W., Zessner, M., Zoboli, O., Zollitsch, W., and Zuvela-Aloise, M.

Abstract

Die Technische Zusammenfassung des APCC-Sonderberichts ″Landnutzung und Klimawandel in Österreich″ umfasst die Kernbotschaften der Kapitel 1–9. In ihr sind die Hauptaussagen zu den sozioökonomischen und klimatischen Treibern der Landnutzungsänderungen, zu den Auswirkungen von Landnutzung und -bewirtschaftung auf den Klimawandel, zu Minderungs- und Anpassungsoptionen im Kontext nachhaltiger Entwicklungsziele sowie zu Synergien, Zielkonflikten und Umsetzungsbarrieren von Klimamaßnahmen enthalten.

Published
2024
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12. Kapitel 3. Sozioökonomische und klimatische Treiber der Änderung der Landnutzung in Österreich

Author

Jandl, R., Tappeiner, U., Foldal, C., Erb, K., Gaube, V., Schneider, S., Thaler, T., Borsky, S., Kirchner, M., Loibl, W., Mehdi-Schulz, B., Schirpke, U., Zuvela-Aloise, M., Jandl, R., Tappeiner, U., Foldal, C., Erb, K., Gaube, V., Schneider, S., Thaler, T., Borsky, S., Kirchner, M., Loibl, W., Mehdi-Schulz, B., Schirpke, U., and Zuvela-Aloise, M.

Abstract

Dieses Kapitel beschäftigt sich mit den klimatischen, ökologischen und sozioökonomischen treibenden Kräften, welche die Landnutzung in Österreich in der Vergangenheit und der Gegenwart maßgeblich bestimmt haben und die zukünftigen Entwicklungen beeinflussen werden. Es behandelt die in der Vergangenheit beobachteten und in der Zukunft erwarteten treibenden Kräfte von Landnutzungsänderungen in der Landwirtschaft (Abschn. 3.2), der Forstwirtschaft (Abschn. 3.3) und der Siedlungs- und Infrastrukturentwicklung (Abschn. 3.4). Abschließend werden die möglichen und erwarteten Auswirkungen dieser treibenden Kräfte auf die Bereitstellung der Ökosystemleistungen (ÖSL) beschrieben (Abschn. 3.5). Der Abbau von Mineralien wie Schotter oder Metalle wird aus Platzgründen nicht in diesem Kapitel behandelt, wenngleich es unumstritten ist, dass es sich auch dabei um landnutzungsrelevante Aktivitäten handelt. Kap. 3 unterscheidet zwischen natürlichen und anthropogenen Faktoren und wie sich diese auf die Landnutzung ausgewirkt haben und auswirken. Die sozioökonomischen Auswirkungen berücksichtigen dabei allerdings nicht die möglichen Anpassungs- oder Minderungsstrategien der einzelnen Sektoren, da diese in den Kap. 4 und 5 gesondert dargestellt werden.

Published
2024
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14. Ultralow phase noise microwave generation with an Er:fiber-based optical frequency divider

Author

Quinlan, F., Fortier, T. M., Kirchner, M. S., Taylor, J. A., Thorpe, M. J., Lemke, N., Ludlow, A. D., Jiang, Y., Oates, C. W., and Diddams, S. A.

Subjects
Physics - Optics
Abstract

We present an optical frequency divider based on a 200 MHz repetition rate Er:fiber mode-locked laser that, when locked to a stable optical frequency reference, generates microwave signals with absolute phase noise that is equal to or better than cryogenic microwave oscillators. At 1 Hz offset from a 10 GHz carrier, the phase noise is below -100 dBc/Hz, limited by the optical reference. For offset frequencies > 10 kHz, the phase noise is shot noise limited at -145 dBc/Hz. An analysis of the contribution of the residual noise from the Er:fiber optical frequency divider is also presented., Comment: 4 pages, 3 figures

Published
2011
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15. The thermal QCD transition with two flavours of twisted mass fermions

Author

Burger, F., Ilgenfritz, E. -M., Kirchner, M., Lombardo, M. P., Muller-Preussker, M., Philipsen, O., Pinke, C., Urbach, C., and Zeidlewicz, L.

Subjects
High Energy Physics - Lattice
Abstract

We investigate the thermal QCD transition with two flavors of maximally twisted mass fermions for a set of pion masses, 300 MeV \textless $m_\pi$ \textless 500 MeV, and lattice spacings $a$ \textless 0.09 fm. We determine the pseudo-critical temperatures and discuss their extrapolation to the chiral limit using scaling forms for different universality classes, as well as the scaling form for the magnetic equation of state. For all pion masses considered we find resonable consistency with O(4) scaling plus leading corrections. However, a true distinction between the O(4) scenario and a first order scenario in the chiral limit requires lighter pions than are currently in use in simulations of Wilson fermions., Comment: 11 pages, 11 figures

Published
2011
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16. Generation of Ultrastable Microwaves via Optical Frequency Division

Author

Fortier, T. M., Kirchner, M. S., Quinlan, F., Taylor, J., Bergquist, J. C., Rosenband, T., Lemke, N., Ludlow, A., Jiang, Y., Oates, C. W., and Diddams, S. A.

Subjects
Physics - Optics, Physics - Instrumentation and Detectors
Abstract

There has been increased interest in the use and manipulation of optical fields to address challenging problems that have traditionally been approached with microwave electronics. Some examples that benefit from the low transmission loss, agile modulation and large bandwidths accessible with coherent optical systems include signal distribution, arbitrary waveform generation, and novel imaging. We extend these advantages to demonstrate a microwave generator based on a high-Q optical resonator and a frequency comb functioning as an optical-to-microwave divider. This provides a 10 GHz electrical signal with fractional frequency instability <8e-16 at 1 s, a value comparable to that produced by the best microwave oscillators, but without the need for cryogenic temperatures. Such a low-noise source can benefit radar systems, improve the bandwidth and resolution of communications and digital sampling systems, and be valuable for large baseline interferometry, precision spectroscopy and the realization of atomic time.

Published
2011
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17. On the phase structure of lattice QCD with twisted-mass Wilson fermions at non-zero temperature

Author

Muller-Preussker, M., Ilgenfritz, E. -M., Jansen, K., Lombardo, M. P., Philipsen, O., Zeidlewicz, L., Kirchner, M., Petschlies, M., Schulze, D., and Urbach, C.

Subjects
High Energy Physics - Lattice
Abstract

In this talk we give an overview of the 3D phase diagram of two-flavour non-zero temperature lattice QCD with twisted-mass Wilson fermions and a tree-level Symanzik-improved gauge action. We present a first feasibility study at maximal twist and, for the quenched case, we demonstrate automatic O(a)-improvement to work., Comment: 7 pages, 12 figures. To appear in the Proceedings of 27th International Symposium on Lattice Field Theory (Lattice 2009), Beijing, China, July 26-31, 2009

Published
2009

19. 178 Longitudinal effects of elexacaftor-tezacaftor-ivacaftor therapy on viscoelastic properties of sputum in people with cystic fibrosis

Author

Kuppe, A., primary, Addante, A., additional, Voller, M., additional, Schaupp, L., additional, Fentker, K., additional, Bardua, M., additional, Duerr, J., additional, Piehler, L., additional, Rohmel, J., additional, Thee, S., additional, Kirchner, M., additional, Ziehm, M., additional, Lauster, D., additional, Haag, R., additional, Gradzielski, M., additional, Stahl, M., additional, Mertins, P., additional, Boutin, S., additional, Graeber, S., additional, and Mall, M., additional

Published
2023
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20. 66 Longitudinal effects of elexacaftor-tezacaftor-ivacaftor therapy on airway infection and inflammation in people with cystic fibrosis

Author

Schaupp, L., primary, Addante, A., additional, Voller, M., additional, Fentker, K., additional, Bardua, M., additional, Kuppe, A., additional, Duerr, J., additional, Piehler, L., additional, Rohmel, J., additional, Thee, S., additional, Kirchner, M., additional, Ziehm, M., additional, Lauster, D., additional, Haag, R., additional, Gradzielski, M., additional, Stahl, M., additional, Mertins, P., additional, Boutin, S., additional, Graeber, S., additional, and Mall, M., additional

Published
2023
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21. Astronomical spectrograph calibration with broad-spectrum frequency combs

Author

Braje, D. A., Kirchner, M. S., Osterman, S., Fortier, T., and Diddams, S. A.

Subjects
Quantum Physics, Astrophysics
Abstract

Broadband femtosecond-laser frequency combs are filtered to spectrographically resolvable frequency-mode spacing, and the limitations of using cavities for spectral filtering are considered. Data and theory are used to show implications to spectrographic calibration of high-resolution, astronomical spectrometers.

Published
2008
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24. In vivo conditions to identify Prkci phosphorylation targets using the analog-sensitive kinase method in zebrafish

Author

Shokat, Kevan, Uhalte, E, Kirchner, M, Hellwig, N, Allen, JJ, Donat, S, Shokat, KM, Selbach, M, and Abdelilah-Seyfried, S

Abstract

Protein kinase C iota is required for various cell biological processes including epithelial tissue polarity and organ morphogenesis. To gain mechanistic insight into different roles of this kinase, it is essential to identify specific substrate proteins i

Published
2012

25. The Impact of Distributed Generation on Power Transmission Grid Dynamics

Author

Newman, D. E., Carreras, B. A., Kirchner, M., and Dobson, I.

Abstract

Implemented monitoring technologies to produce real-time ratings (RTR) of transmission lines and evaluated the use of RTR to mitigate both the power transfer into a large multi-utility transmission area and the voltage constraints within a large area.

Published
2011

26. Carrion converging: Skull shape predicts feeding ecology in vultures.

Author

Steinfield, K. R., Felice, R. N., Kirchner, M. E., and Knapp, A.

Subjects
ANIMAL feeds, FISHER discriminant analysis, SKULL, VULTURES, ANIMAL carcasses, BEHAVIORAL assessment
Abstract

The link between skull shape and dietary ecology in birds at macroevolutionary scales has recently been called into question by analyses of 3D shape that reveal that cranial anatomy is mainly influenced by other factors such as allometry. It is still unknown whether this form‐function disconnect also exists at smaller evolutionary scales, for example within specialized ecological guilds. Vultures are a diverse guild of 23 extant species in two families (Accipitridae and Cathartidae) that exhibit evolutionary convergence as a result of highly specialized feeding ecology. Vultures are the only known obligate scavengers among vertebrates and are usually grouped together under this single dietary category, but within this specialized diet there are three distinct, species‐specific feeding strategies termed ripper, gulper, and scrapper. We use three‐dimensional geometric morphometrics to quantify the relative contributions of feeding ecology, allometry, and phylogeny on vulture skull shape, along with several non‐vulture raptors of similar size, range and ecology. Families show clear separation in shape, but phylogenetic signal is comparatively weak (Kmult = 0.33). Taking into account the influence of phylogeny, skull shape is not significantly correlated with either skull size or feeding type, but there are examples of strong, significant convergence and parallel shape evolution across feeding groups. Furthermore, skull shape performs strongly in predicting feeding ecology in a phylogenetic discriminant function analysis. These findings highlight the importance of detailed assessment of feeding behavior in studies of ecomorphology, rather than broader dietary categories alone, and reveal that ecology can be readily inferred from form given appropriate information. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN

Author

Fuchs, S., Danßmann, C., Klironomos, F., Winkler, A., Fallmann, J., Kruetzfeldt, L.M., Szymansky, A., Naderi, J., Bernhart, S.H., Grunewald, L., Helmsauer, K., Rodriguez-Fos, E., Kirchner, M., Mertins, P., Astrahantseff, K., Suenkel, C., Toedling, J., Meggetto, F., Remke, M., Stadler, P.F., Hundsdoerfer, P., Deubzer, H.E., Künkele, A., Lang, P., Fuchs, J., Henssen, A.G., Eggert, A., Rajewsky, N., Hertwig, F., and Schulte, J.H.

Subjects
Cancer Research, Cardiovascular and Metabolic Diseases, Technology Platforms
Abstract

Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.

Published
2023

30. Improvement of the Welfare Quality scoring model for dairy cows to fit experts' opinion

Author

Lardy, R, Botreau, R, de Boyer des Roches, A, van Eerdenburg, F J C M, de Graaf, S, Haskell, M J, Kirchner, M K, Mounier, L, Kjosevski, M, Tuyttens, F A M, Veissier, I, Lardy, R, Botreau, R, de Boyer des Roches, A, van Eerdenburg, F J C M, de Graaf, S, Haskell, M J, Kirchner, M K, Mounier, L, Kjosevski, M, Tuyttens, F A M, and Veissier, I

Abstract

After several years of implementation, the original Welfare Quality scoring model for dairy cows appears to be highly sensitive to the number and cleanliness of drinkers and not enough to the prevalence of diseases, and as a consequence may not fit the opinion of some animal welfare experts. The present paper aims to improve the Welfare Quality calculations for the criteria 'Absence of prolonged thirst' and 'Absence of disease' in dairy cows, so that the results are more sensitive to input data and better fit experts' opinion. First, we modified the calculation of 'Absence of prolonged thirst' by linearising the calculation for drinkers' availability to avoid threshold effects. Second, we modified the calculation of 'Absence of disease' by applying a Choquet integral on the three lowest spline-based scores for each health disorder to limit compensation between health disorders. Third, we performed a global sensitivity analysis of the original and the alternative scoring models. Fourth, we compared the results obtained with the original and the alternative models with eight experts' opinions on two subsets composed of 44 and 60 farms, respectively, inspected using the Welfare Quality protocol and on which experts gave their opinion on the overall level of animal welfare. Results show that the alternative model significantly reduced the 'threshold effects' related to the number of drinkers and the compensation between health disorders. On the first subset, the alternative model fits the experts' opinion slightly better than the original model (P = 0.061). On the second subset, the models performed equally. In conclusion, the proposed refinements for calculating scores are validated since they significantly reduced 'threshold effects' and the influence of measures related to drinkers. It also reduced the compensation between health disorders by considering only the three lowest scores and thus increasing the influence of measures related to health disorders, and sli

Published
2023

32. Past and future impacts of land-use changes on ecosystem services in Austria

Author

Schirpke, U., Tasser, E., Borsky, S., Braun, M., Eitzinger, J., Gaube, V., Getzner, M., Glatzel, S., Gschwantner, T., Kirchner, M., Leitinger, G., Mehdi-Schulz, B., Mitter, H., Scheifinger, H., Thaler, S., Thom, D., Thaler, T., Schirpke, U., Tasser, E., Borsky, S., Braun, M., Eitzinger, J., Gaube, V., Getzner, M., Glatzel, S., Gschwantner, T., Kirchner, M., Leitinger, G., Mehdi-Schulz, B., Mitter, H., Scheifinger, H., Thaler, S., Thom, D., and Thaler, T.

Abstract

Environmental and socio-economic developments induce land-use changes with potentially negative impacts on human well-being. To counteract undesired developments, a profound understanding of the complex relationships between drivers, land use, and ecosystem services is needed. Yet, national studies examining extended time periods are still rare. Based on the Special Report on land use, land management and climate change by the Austrian Panel on Climate Change (APCC), we use the Driver-Pressure-State-Impact-Response (DPSIR) framework to (1) identify the main drivers of land-use change, (2) describe past and future land-use changes in Austria between 1950 and 2100, (3) report related impacts on ecosystem services, and (4) discuss management responses. Our findings indicate that socio-economic drivers (e.g., economic growth, political systems, and technological developments) have influenced past land-use changes the most. The intensification of agricultural land use and urban sprawl have primarily led to declining ecosystem services in the lowlands. In mountain regions, the abandonment of mountain grassland has prompted a shift from provisioning to regulating services. However, simulations indicate that accelerating climate change will surpass socio-economic drivers in significance towards the end of this century, particularly in intensively used agricultural areas. Although climate change-induced impacts on ecosystem services remain uncertain, it can be expected that the range of land-use management options will be restricted in the future. Consequently, policymaking should prioritize the development of integrated land-use planning to safeguard ecosystem services, accounting for future environmental and socio-economic uncertainties.

Published
2023
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33. Improvement of the Welfare Quality scoring model for dairy cows to fit experts' opinion

Author

FAH veterinaire epidemiologie, Lardy, R, Botreau, R, de Boyer des Roches, A, van Eerdenburg, F J C M, de Graaf, S, Haskell, M J, Kirchner, M K, Mounier, L, Kjosevski, M, Tuyttens, F A M, Veissier, I, FAH veterinaire epidemiologie, Lardy, R, Botreau, R, de Boyer des Roches, A, van Eerdenburg, F J C M, de Graaf, S, Haskell, M J, Kirchner, M K, Mounier, L, Kjosevski, M, Tuyttens, F A M, and Veissier, I

Published
2023

34. Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators

Author

Kühnisch, J., Theisen, S., Dartsch, J., Fritsche-Guenther, R., Kirchner, M., Obermayer, B., Bauer, A., Kahlert, A.K., Rothe, M., Beule, D., Heuser, A., Mertins, P., Kirwan, J.A., Berndt, N., MacRae, C.A., Hubner, N., and Klaassen, S.

Subjects
Cardiovascular and Metabolic Diseases, Technology Platforms
Abstract

BACKGROUND: Mutation of the PRDM16 gene has been associated with human cardiomyopathy. The PRDM16 protein is a transcriptional regulator affecting cardiac development via Tbx5 and Hand1 regulating myocardial structure. Biallelic Prdm16 inactivation induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. Early pathological events upon Prdm16 inactivation have not been explored. METHODS: This study performed in depth pathophysiological and molecular analysis of male and female Prdm16csp1/wt mice carrying systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes with transcriptomics, proteomics, and metabolomics. Kinetic modelling of the cardiac metabolism was undertaken in silico with CARDIOKIN. RESULTS: Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt hearts demonstrate moderate alterations of specific transcripts and protein levels with consistent upregulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre B-cell leukemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional upregulation was detected for Prdm16 itself probably by an autoregulatory mechanism. Prdm16csp1/wt cardiac tissue showed reduction of metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and tricarboxylic acid cycle. Global lipid metabolism was also affected with accumulation of triacylglycerides detected in male Prdm16csp1/wt hearts. In addition, Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. Metabolic modelling in silico suggested lowered fatty acid utilization in male and reduced glucose utilization in female Prdm16csp1/wt cardiac tissue. CONCLUSIONS: Monoallelic Prdm16 mutation restricts cardiac performance in Prdm16csp1/wt mice.Metabolic alterations precede transcriptional dysregulation in Prdm16csp1/wt cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype indicating a sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in PRDM16 associated cardiac pathology.

Published
2023

37. EP08.01-031 Blood Gene Expression Changes in Metastatic Lung Cancer under second-line Immunotherapy according to Clinical Response

Author

Lusky, F., primary, Schindler, H., additional, Elshiaty, M., additional, Gaissmaier, L., additional, Daniello, L., additional, Bozorgmehr, F., additional, Kuon, J., additional, Shah, R., additional, Schneider, M.A., additional, Eichhorn, F., additional, Trudzinski, F., additional, Angeles, A., additional, Janke, F., additional, Kirchner, M., additional, Kazdal, D., additional, Stenzinger, A., additional, Sültmann, H., additional, Thomas, M., additional, and Christopoulos, P., additional

Published
2022
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38. 1505P Exploratory biomarker analysis of the NEONAX trial for response prediction to perioperative (PO) and adjuvant (A) Gem-nabPac chemotherapy (CTX) in resectable PDAC patients (rPDAC Pts)

Author

Lahusen, A., Ettrich, T.J., Kirchner, M., Kluck, K., Wisser, S., Uhl, W., Kornmann, M., Algül, H., Friess, H., Koenig, A.O., Kleger, A., Schuhbaur, J., Perkhofer, L., Budczies, J., Tempero, M.A., Reinacher-Schick, A., Stenzinger, A., Tannapfel, A., Eiseler, T., and Seufferlein, T.

Published
2024
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41. S101: GENETIC AND EPIGENETIC FACTORS DRIVING PRIMARY MEDIASTINAL B-CELL LYMPHOMA PATHOGENESIS AND OUTCOME

Author

Noerenberg, D., primary, Briest, F., additional, Hennch, C., additional, Yoshida, K., additional, Nimo, J., additional, Hablesreiter, R., additional, Takeuchi, Y., additional, Sasca, D., additional, Ueno, H., additional, Mansouri, L., additional, Inoue, Y., additional, Wiegand, L., additional, Staiger, A. M., additional, Casadei, B., additional, Ziepert, M., additional, Asmar, F., additional, Korkolopoulou, P., additional, Kirchner, M., additional, Mertins, P., additional, Weiner, J., additional, Toth, E., additional, Weber, T., additional, Warth, A., additional, Schneider, T., additional, Amini, R.-M., additional, Klapper, W., additional, Hummel, M., additional, Poeschel, V., additional, Kanellis, G., additional, Rosenwald, A., additional, Held, G., additional, Campo, E., additional, Stamatopoulos, K., additional, Anagnostopoulos, I., additional, Bullinger, L., additional, Goldschmidt, N., additional, Zinzani, P. L., additional, Bödor, C., additional, Rosenquist, R., additional, Vassilakopoulos, T. P., additional, Ott, G., additional, Ogawa, S., additional, and Damm, F., additional

Published
2022
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43. ROBOCOP II: eine randomisiert-kontrollierte Studie zur offenen versus roboter-assistierten Nierenteilresektion

Author

Kowalewski, K., Sidoti Abata, M., Neuberger, M., Kirchner, M., Krisam, R., Egen, L., Haney, C., Siegel, F., Michel, M., Honeck, P., Nuhn, P., Westhoff, N., and Kriegmair, M.

Subjects
ddc: 610, Medicine and health
Abstract

Einleitung: Die Nierenteilresektion (PN) stellt den Goldstandard zur Behandlung des lokalisierten Nierenzellkarzinom in kurativer Intention dar. Bisher gibt es keine Daten aus randomisiert-kontrollierten Studien (RCT), die die roboter-assistierte partielle Nephrektomie (RAPN) mit der offenen PN (OPN) [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022
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46. The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Author

Enginyeria Electrònica, Elèctrica i Automàtica, Universitat Rovira i Virgili, Taha, HM; Aalizadeh, R; Alygizakis, N; Antignac, JP; Arp, HPH; Bade, R; Baker, N; Belova, L; Bijlsma, L; Bolton, EE; Brack, W; Celma, A; Chen, WL; Cheng, TJ; Chirsir, P; Cirka, L; D'Agostino, LA; Feunang, YD; Dulio, V; Fischer, S; Gago-Ferrero, P; Galani, A; Geueke, B; Glowacka, N; Gluge, J; Groh, K; Grosse, S; Haglund, P; Hakkinen, PJ; Hale, SE; Hernandez, F; Janssen, EML; Jonkers, T; Kiefer, K; Kirchner, M; Koschorreck, J; Krauss, M; Krier, J; Lamoree, MH; Letzel, M; Letzel, T; Li, QL; Little, J; Liu, YN; Lunderberg, DM; Martin, JW; McEachran, AD; McLean, JA; Meier, C; Meijer, J; Menger, F; Merino, C; Muncke, J; Muschket, M; Neumann, M; Neveu, V; Ng, K; Oberacher, H; O'Brien, J; Oswald, P; Oswaldova, M; Picache, JA; Postigo, C; Ramirez, N; Reemtsma, T; Renaud, J; Rostkowski, P; Rudel, H; Salek, RM; Samanipour, S; Scheringer, M; Schliebner, I; Schulz, W; Schulze, T; Sengl, M; Shoemaker, BA; Sims, K; Singer, H; Singh, RR; Sumarah, M; Thiessen, PA; Thomas, KV; Torres, S; Trier, X; van Wezel, AP; Vermeulen, RCH; Vlaanderen, JJ; von der Ohe, PC; Wang, ZY; Williams, AJ; Willighagen, EL; Wishart, DS; Zhang, J; Thomaidis, NS; Hollender, J; Slobodnik, J; Schymanski, EL, Enginyeria Electrònica, Elèctrica i Automàtica, Universitat Rovira i Virgili, and Taha, HM; Aalizadeh, R; Alygizakis, N; Antignac, JP; Arp, HPH; Bade, R; Baker, N; Belova, L; Bijlsma, L; Bolton, EE; Brack, W; Celma, A; Chen, WL; Cheng, TJ; Chirsir, P; Cirka, L; D'Agostino, LA; Feunang, YD; Dulio, V; Fischer, S; Gago-Ferrero, P; Galani, A; Geueke, B; Glowacka, N; Gluge, J; Groh, K; Grosse, S; Haglund, P; Hakkinen, PJ; Hale, SE; Hernandez, F; Janssen, EML; Jonkers, T; Kiefer, K; Kirchner, M; Koschorreck, J; Krauss, M; Krier, J; Lamoree, MH; Letzel, M; Letzel, T; Li, QL; Little, J; Liu, YN; Lunderberg, DM; Martin, JW; McEachran, AD; McLean, JA; Meier, C; Meijer, J; Menger, F; Merino, C; Muncke, J; Muschket, M; Neumann, M; Neveu, V; Ng, K; Oberacher, H; O'Brien, J; Oswald, P; Oswaldova, M; Picache, JA; Postigo, C; Ramirez, N; Reemtsma, T; Renaud, J; Rostkowski, P; Rudel, H; Salek, RM; Samanipour, S; Scheringer, M; Schliebner, I; Schulz, W; Schulze, T; Sengl, M; Shoemaker, BA; Sims, K; Singer, H; Singh, RR; Sumarah, M; Thiessen, PA; Thomas, KV; Torres, S; Trier, X; van Wezel, AP; Vermeulen, RCH; Vlaanderen, JJ; von der Ohe, PC; Wang, ZY; Williams, AJ; Willighagen, EL; Wishart, DS; Zhang, J; Thomaidis, NS; Hollender, J; Slobodnik, J; Schymanski, EL

Abstract

Background: The NORMAN Association (https://www.norman-.network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-.network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo.org/communities/norman-.sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN

Published
2022

49. Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial

Author

Ware, Julia, primary, Boughton, Charlotte K, additional, Allen, Janet M, additional, Wilinska, Malgorzata E, additional, Tauschmann, Martin, additional, Denvir, Louise, additional, Thankamony, Ajay, additional, Campbell, Fiona M, additional, Wadwa, R Paul, additional, Buckingham, Bruce A, additional, Davis, Nikki, additional, DiMeglio, Linda A, additional, Mauras, Nelly, additional, Besser, Rachel E J, additional, Ghatak, Atrayee, additional, Weinzimer, Stuart A, additional, Hood, Korey K, additional, Fox, D Steven, additional, Kanapka, Lauren, additional, Kollman, Craig, additional, Sibayan, Judy, additional, Beck, Roy W, additional, Hovorka, Roman, additional, Hovorka, R, additional, Acerini, C L, additional, Thankamony, A, additional, Allen, J M, additional, Boughton, C K, additional, Dovc, K, additional, Dunger, D B, additional, Ware, J, additional, Musolino, G, additional, Tauschmann, M, additional, Wilinska, M E, additional, Hayes, J F, additional, Hartnell, S, additional, Slegtenhorst, S, additional, Ruan, Y, additional, Haydock, M, additional, Mangat, J, additional, Denvir, L, additional, Kanthagnany, SK, additional, Law, J, additional, Randell, T, additional, Sachdev, P, additional, Saxton, M, additional, Coupe, A, additional, Stafford, S, additional, Ball, A, additional, Keeton, R, additional, Cresswell, R, additional, Crate, L, additional, Cripps, H, additional, Fazackerley, H, additional, Looby, L, additional, Navarra, H, additional, Saddington, C, additional, Smith, V, additional, Verhoeven, V, additional, Bratt, S, additional, Khan, N, additional, Moyes, L, additional, Sandhu, K, additional, West, C, additional, Wadwa, R P, additional, Alonso, G, additional, Forlenza, G, additional, Slover, R, additional, Towers, L, additional, Berget, C, additional, Coakley, A, additional, Escobar, E, additional, Jost, E, additional, Lange, S, additional, Messer, L, additional, Thivener, K, additional, Campbell, F M, additional, Yong, J, additional, Metcalfe, E, additional, Allen, M, additional, Ambler, S, additional, Waheed, S, additional, Exall, J, additional, Tulip, J, additional, Buckingham, B A, additional, Ekhlaspour, L, additional, Maahs, D, additional, Norlander, L, additional, Jacobson, T, additional, Twon, M, additional, Weir, C, additional, Leverenz, B, additional, Keller, J, additional, Davis, N, additional, Kumaran, A, additional, Trevelyan, N, additional, Dewar, H, additional, Price, G, additional, Crouch, G, additional, Ensom, R, additional, Haskell, L, additional, Lueddeke, LM, additional, Mauras, N, additional, Benson, M, additional, Bird, K, additional, Englert, K, additional, Permuy, J, additional, Ponthieux, K, additional, Marrero-Hernandez, J, additional, DiMeglio, L A, additional, Ismail, H, additional, Jolivette, H, additional, Sanchez, J, additional, Woerner, S, additional, Kirchner, M, additional, Mullen, M, additional, Tebbe, M, additional, Besser, R EJ, additional, Basu, S, additional, London, R, additional, Makaya, T, additional, Ryan, F, additional, Megson, C, additional, Bowen-Morris, J, additional, Haest, J, additional, Law, R, additional, Stamford, I, additional, Ghatak, A, additional, Deakin, M, additional, Phelan, K, additional, Thornborough, K, additional, Shakeshaft, J, additional, Weinzimer, S A, additional, Cengiz, E, additional, Sherr, J L, additional, Van Name, M, additional, Weyman, K, additional, Carria, L, additional, Steffen, A, additional, Zgorski, M, additional, Sibayan, J, additional, Beck, R W, additional, Borgman, S, additional, Davis, J, additional, Rusnak, J, additional, Hellman, A, additional, Cheng, P, additional, Kanapka, L, additional, Kollman, C, additional, McCarthy, C, additional, Chalasani, S, additional, Hood, K K, additional, Hanes, S, additional, Viana, J, additional, Lanning, M, additional, Fox, D S, additional, Arreaza-Rubin, G, additional, Eggerman, T, additional, Green, N, additional, Janicek, R, additional, Gabrielson, D, additional, Belle, S H, additional, Castle, J, additional, Green, J, additional, Legault, L, additional, Willi, S M, additional, and Wysham, C, additional

Published
2022
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50. HHG at the Carbon K-edge directly driven by SRS red-shifted pulses from an Yb amplifier

Author

Kirchner, M., Shumakova, V., Coccia, G., Kaksis, E., Schmidt, B., Pervak, V., Pugzlys, A., Zeiler, M., Baltuska, A., and Paolo Antonio Carpeggiani

Abstract

HHG in gases is driven with pulses from an Yb:CaF2 amplifier post-compressed and redshifted in a nitrogen-filled stretched hollow core fiber. With this driving scheme, we experimentally demonstrated the extension of the HHG cut-off to the Carbon K-edge without the need for laser frequency conversion via parametric processes.

Published
2022

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