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3. Digital high-pass filter deconvolution by means of an infinite impulse response filter

Author

Födisch, P., Wohsmann, J., Lange, B., Schönherr, J., Enghardt, W., and Kaever, P.

Subjects
Physics - Instrumentation and Detectors
Abstract

In the application of semiconductor detectors, the charge-sensitive amplifier is widely used in front-end electronics. The output signal is shaped by a typical exponential decay. Depending on the feedback network, this type of front-end electronics suffers from the ballistic deficit problem, or an increased rate of pulse pile-ups. Moreover, spectroscopy applications require a correction of the pulse-height, while a shortened pulse-width is desirable for high-throughput applications. For both objectives, digital deconvolution of the exponential decay is convenient. With a general method and the signals of our custom charge-sensitive amplifier for cadmium zinc telluride detectors, we show how the transfer function of an amplifier is adapted to an infinite impulse response (IIR) filter. This paper investigates different design methods for an IIR filter in the discrete-time domain and verifies the obtained filter coefficients with respect to the equivalent continuous-time frequency response. Finally, the exponential decay is shaped to a step-like output signal that is exploited by a forward-looking pulse processing.

Published
2016
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4. ELSI: A unified software interface for Kohn–Sham electronic structure solvers

Author

Yu, VWZ, Corsetti, F, García, A, Huhn, WP, Jacquelin, M, Jia, W, Lange, B, Lin, L, Lu, J, Mi, W, Seifitokaldani, A, Vázquez-Mayagoitia, Á, Yang, C, Yang, H, and Blum, V

Subjects
Density-functional theory, Kohn-Sham eigenvalue problem, Parallel computing, physics.comp-ph, cond-mat.mtrl-sci, Nuclear & Particles Physics, Mathematical Sciences, Physical Sciences, Information and Computing Sciences
Abstract

Solving the electronic structure from a generalized or standard eigenproblem is often the bottleneck in large scale calculations based on Kohn–Sham density-functional theory. This problem must be addressed by essentially all current electronic structure codes, based on similar matrix expressions, and by high-performance computation. We here present a unified software interface, ELSI, to access different strategies that address the Kohn–Sham eigenvalue problem. Currently supported algorithms include the dense generalized eigensolver library ELPA, the orbital minimization method implemented in libOMM, and the pole expansion and selected inversion (PEXSI) approach with lower computational complexity for semilocal density functionals. The ELSI interface aims to simplify the implementation and optimal use of the different strategies, by offering (a) a unified software framework designed for the electronic structure solvers in Kohn–Sham density-functional theory; (b) reasonable default parameters for a chosen solver; (c) automatic conversion between input and internal working matrix formats, and in the future (d) recommendation of the optimal solver depending on the specific problem. Comparative benchmarks are shown for system sizes up to 11,520 atoms (172,800 basis functions) on distributed memory supercomputing architectures. Program summary Program title: ELSI Interface Program Files doi: http://dx.doi.org/10.17632/y8vzhzdm62.1 Licensing provisions: BSD 3-clause Programming language: Fortran 2003, with interface to C/C++ External routines/libraries: MPI, BLAS, LAPACK, ScaLAPACK, ELPA, libOMM, PEXSI, ParMETIS, SuperLU_DIST Nature of problem: Solving the electronic structure from a generalized or standard eigenvalue problem in calculations based on Kohn–Sham density functional theory (KS-DFT). Solution method: To connect the KS-DFT codes and the KS electronic structure solvers, ELSI provides a unified software interface with reasonable default parameters, hierarchical control over the interface and the solvers, and automatic conversions between input and internal working matrix formats. Supported solvers are: ELPA (dense generalized eigensolver), libOMM (orbital minimization method), and PEXSI (pole expansion and selected inversion method). Restrictions: The ELSI interface requires complete information of the Hamiltonian matrix.

Published
2018

5. Charge-sensitive front-end electronics with operational amplifiers for CdZnTe detectors

Author

Födisch, P., Berthel, M., Lange, B., Kirschke, T., Enghardt, W., and Kaever, P.

Subjects
Physics - Instrumentation and Detectors
Abstract

Cadmium zinc telluride (CdZnTe, CZT) radiation detectors are suitable for a variety of applications, due to their high spatial resolution and spectroscopic energy performance at room temperature. However, state-of-the-art detector systems require high-performance readout electronics. Though an application-specific integrated circuit (ASIC) is an adequate solution for the readout, requirements of high dynamic range and high throughput are not available in any commercial circuit. Consequently, the present study develops the analog front-end electronics with operational amplifiers for an 8x8 pixelated CZT detector. For this purpose, we modeled an electrical equivalent circuit of the CZT detector with the associated charge-sensitive amplifier (CSA). Based on a detailed network analysis, the circuit design is completed by numerical values for various features such as ballistic deficit, charge-to-voltage gain, rise time, and noise level. A verification of the performance is carried out by synthetic detector signals and a pixel detector. The experimental results with the pixel detector assembly and a 22Na radioactive source emphasize the depth dependence of the measured energy. After pulse processing with depth correction based on the fit of the weighting potential, the energy resolution is 2.2% (FWHM) for the 511 keV photopeak.

Published
2016
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6. A synchronous Gigabit Ethernet protocol stack for high-throughput UDP/IP applications

Author

Födisch, P., Lange, B., Sandmann, J., Büchner, A., Enghardt, W., and Kaever, P.

Subjects
Physics - Instrumentation and Detectors
Abstract

State of the art detector readout electronics require high-throughput data acquisition (DAQ) systems. In many applications, e. g. for medical imaging, the front-end electronics are set up as separate modules in a distributed DAQ. A standardized interface between the modules and a central data unit is essential. The requirements on such an interface are varied, but demand almost always a high throughput of data. Beyond this challenge, a Gigabit Ethernet interface is predestined for the broad requirements of Systems-on-a-Chip (SoC) up to large-scale DAQ systems. We have implemented an embedded protocol stack for a Field Programmable Gate Array (FPGA) capable of high-throughput data transmission and clock synchronization. A versatile stack architecture for the User Datagram Protocol (UDP) and Internet Control Message Protocol (ICMP) over Internet Protocol (IP) such as Address Resolution Protocol (ARP) as well as Precision Time Protocol (PTP) is presented. With a point-to-point connection to a host in a MicroTCA system we achieved the theoretical maximum data throughput limited by UDP both for 1000BASE-T and 1000BASE-KX links. Furthermore, we show that the random jitter of a synchronous clock over a 1000BASE-T link for a PTP application is below 60 ps.

Published
2015
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8. Outbreak of SARS-CoV-2 in a geriatric acute-care ward during summer 2023: current aspects of infection control in the postpandemic period

Author

Lange, B, Mesquita, G, Burkhardt, H, Gerigk, M, Heininger, A, Lange, B, Mesquita, G, Burkhardt, H, Gerigk, M, and Heininger, A

Abstract

Aim: Management of a SARS-CoV-2 outbreak in geriatric patients, taking into account the transition to the post-pandemic period. Methods: PCR tests were conducted to identify the scale of infection during the outbreak; no new patients were admitted to the ward until the availability of the PCR results. Based on the results and individual risk assessment, three cohorts were formed and treated as recommended by the RKI. After terminating the admissions stop, new admissions received PCR screening. Contact patients were retested on days 3 and 5. Employees carried out self-monitoring, and if symptoms developed, an antigen test was performed.Results: Nine of the 11 PCR-positive patients (6m, 5f), median age 85 years, were immunized. Eight patients were symptomatic, ten received antiviral therapy and two required intensive care. Three symptomatic employees had a positive antigen test. Patients without direct contact to the positive cases who initially tested negative and the 16 new admissions with a negative PCR test did not contract COVID-19. Outbreak management ended after 15 days without deaths from COVID-19.Conclusion: During the outbreak, PCR screening, the temporary stop in new admission until the availability of PCR results, and the risk-adapted cohorting of patients supplemented by consistent PCR tests of new admissions formed the basis for successful outbreak management. Treatment can be made possible despite high vulnerability. Close symptom monitoring and rapid implementation of measures reduce the risk. Repeated PCRs of direct-contact patients on day 3 can warrant pre-emptive antiviral therapy despite being asymptomatic; testing on day 5 makes it possible to shorten preventive isolation measures. The use of protective masks and self-monitoring by employees are fundamental to preventing further infections., Hintergrund: Management eines SARS-CoV-2-Ausbruchs bei geriatrischen Patienten unter Berücksichtigung des Übergangs in die endemische Situation.Methoden: Im Ausbruch erfolgte zur Klärung der Infektionssituation ein PCR-Screening und bis zum Vorliegen der Ergebnisse ein kurzer Aufnahme-Stopp. Anhand der PCR-Ergebnisse wurden drei risikoadaptierte Kohorten gebildet, die gemäß RKI behandelt wurden. Mit Ende des Aufnahme-Stopps erhielten Neuaufnahmen ein PCR-Screening. Kontaktpatienten wurden an Tag 3 und 5 erneut getestet. Mitarbeiter führten ein Selbstmonitoring und bei Symptomen einen Antigentest durch.Ergebnisse: Neun der 11 PCR-positiven Patienten (6m, 5w), Altersmedian 85 Jahre, waren grundimmunisiert. Symptomatisch waren acht, eine antivirale Therapie erhielten 10 Patienten. Zwei wurden intensivmedizinisch behandelt. Drei symptomatische Mitarbeiter hatten einen positiven Antigentest. Alle initial PCR-negativ getesteten Patienten ohne direkten Kontakt und 16 PCR-negativ getestete Neuaufnahmen erkrankten nicht an COVID-19. Das Ausbruchmanagement endete nach 15 Tagen. Kein Patient verstarb an COVID-19.Diskussion: Im Ausbruch sind PCR-Screening, ein passagerer Aufnahme-Stopp bis zum Vorliegen der Ergebnisse und die risikoadaptierte Kohortierung der Patienten die Basis für ein erfolgreiches Ausbruchmanagement. Ergänzt durch ein konsequentes Aufnahmescreening kann die Behandlung trotz hoher Vulnerabilität ermöglicht werden. Engmaschige Symptombeobachtung und zeitnahes Handeln senken das Risiko. Die PCR-Testung direkter Kontaktpatienten an Tag 3 dient bei positivem Resultat der Veranlassung einer präemptiven antiviralen Therapie begründen; Testung an Tag 5 dient der Verkürzung der Quarantäne. Mitarbeiter sollten Schutzmasken tragen, um - ergänzt durch ein Selbstmonitoring - weitere Ansteckungen zu verhindern.

Published
2024

9. Compositional clusters in the nasal microbiome as predictors of SARS-CoV-2 infection - results from the German National Cohort (NAKO) study

Author

Kleine Bardenhorst, S, Six-Merker, J, Peters, A, Krist, L, Keil, T, Nimptsch, K, Pischon, T, Gastell, S, Schulze, MB, Wolters, M, Günther, K, Schikowski, T, Schmidt, B, Stang, A, Michels, KB, Klee, B, Mikolajczyk, R, Harth, V, Obi, N, Lange, B, Klett-Tammen, CJ, Lieb, W, Becher, H, Kaaks, R, Karch, A, Berger, K, Nauck, M, Khattak M, N, Baurecht, H, Leitzmann, M, Holleczek, B, Brenner, H, Kemmling, Y, Panreck, L, Vital, M, Rübsamen, N, Kleine Bardenhorst, S, Six-Merker, J, Peters, A, Krist, L, Keil, T, Nimptsch, K, Pischon, T, Gastell, S, Schulze, MB, Wolters, M, Günther, K, Schikowski, T, Schmidt, B, Stang, A, Michels, KB, Klee, B, Mikolajczyk, R, Harth, V, Obi, N, Lange, B, Klett-Tammen, CJ, Lieb, W, Becher, H, Kaaks, R, Karch, A, Berger, K, Nauck, M, Khattak M, N, Baurecht, H, Leitzmann, M, Holleczek, B, Brenner, H, Kemmling, Y, Panreck, L, Vital, M, and Rübsamen, N

Published
2024

16. Assessing effects of Cannabis on various neuropathologies: A systematic review

Author

Pathak, S, Jeyabalan, JB, Liu, K, Cook, P, Lange, B, Kim, S, Nadar, R, Ward, K, Watts Alexander, CS, Kumar, A, Dua, K, Moore, T, Govindasamy, J, Dhanasekaran, M, Pathak, S, Jeyabalan, JB, Liu, K, Cook, P, Lange, B, Kim, S, Nadar, R, Ward, K, Watts Alexander, CS, Kumar, A, Dua, K, Moore, T, Govindasamy, J, and Dhanasekaran, M

Published
2024

19. Factorization and Shape-Function Effects in Inclusive B-Meson Decays

Author

Bosch, S. W., Lange, B. O., Neubert, M., and Paz, G.

Subjects
High Energy Physics - Phenomenology
Abstract

Using methods of effective field theory, factorized expressions for arbitrary B -> X_u l nu decay distributions in the shape-function region of large hadronic energy and moderate hadronic invariant mass are derived. Large logarithms are resummed at next-to-leading order in renormalization-group improved perturbation theory. The operator product expansion is employed to relate moments of the renormalized shape function with HQET parameters such as m_b, Lambda(bar) and lambda_1 defined in a new physical subtraction scheme. An analytic expression for the asymptotic behavior of the shape function is obtained, which reveals that it is not positive definite. Explicit expressions are presented for the charged-lepton energy spectrum, the hadronic invariant mass distribution, and the spectrum in the hadronic light-cone momentum P_+ = E_H - P_H. A new method for a precision measurement of |V_{ub}| is proposed, which combines good theoretical control with high efficiency and a powerful discrimination against charm background., Comment: 51 pages, 10 figures; minor corrections, version to appear in Nuclear Physics B

Published
2004
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20. Factorization and Sudakov Resummation in Leptonic Radiative B Decay

Author

Bosch, S. W., Hill, R. J., Lange, B. O., and Neubert, M.

Subjects
High Energy Physics - Phenomenology
Abstract

Soft-collinear effective theory is used to prove factorization of the B->gamma+l+nu decay amplitude at leading power in Lambda/m_b, including a demonstration of the absence of non-valence Fock states and of the finiteness of the convolution integral in the factorization formula. Large logarithms entering the hard-scattering kernel are resummed by performing a two-step perturbative matching onto the low-energy effective theory, and by solving evolution equations derived from the renormalization properties of the leading-order B-meson light-cone distribution amplitude. As a byproduct, the evolution equation for heavy-collinear current operators in soft-collinear effective theory is derived., Comment: 20 pages, 5 figures; several references added or updated, extended discussion of the new elements of the factorization proof, typo in eq.(6) fixed; version to appear in Phys. Rev. D

Published
2003
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23. Bridging the gap – estimation of 2022/2023 SARS-CoV-2 healthcare burden in Germany based on multidimensional data from a rapid epidemic panel

Author

Harries, M, primary, Jaeger, V.K, additional, Rodiah, I, additional, Hassenstein, M.J, additional, Ortmann, J, additional, Dreier, M, additional, von Holt, I, additional, Brinkmann, M, additional, Dulovic, A, additional, Gornyk, D, additional, Hovardovska, O, additional, Kuczewski, C, additional, Kurosinski, MA, additional, Schlotz, M, additional, Schneiderhan-Marra, N, additional, Strengert, M, additional, Krause, G, additional, Sester, M, additional, Klein, F, additional, Petersmann, A, additional, Karch, A, additional, and Lange, B, additional

Published
2023
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25. Proteomic Survey of Metabolic Pathways in Rice

Author

Koller, Antonius, Washburn, Michael P., Lange, B. Markus, Andon, Nancy L., Deciu, Cosmin, Haynes, Paul A., Hays, Lara, Schieltz, David, Ulaszek, Ryan, Wei, Jing, Wolters, Dirk, and Yates, John R.

Published
2002

32. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations

Author

Sherratt, K., Gruson, H., Grah, R., Johnson, H., Niehus, R., Prasse, B., Sandmann, F., Deuschel, J., Wolffram, D., Abbott, S., Ullrich, A., Gibson, G., Ray, E. L., Reich, N. G., Sheldon, D., Wang, Y., Wattanachit, N., Wang, L., Trnka, J., Obozinski, G., Sun, T., Thanou, D., Pottier, L., Krymova, E., Meinke, J. H., Barbarossa, M. V., Leithäuser, N., Mohring, J., Schneider, J., Wlazlo, J., Fuhrmann, J., Lange, B., Rodiah, I., Baccam, P., Gurung, H., Stage, S., Suchoski, B., Budzinski, J., Walraven, R., Villanueva, I., Tucek, V., Smíd, M., Zajícek, M., Pérez Alvarez, C., Reina, B., Bosse, N. I., Meakin, S., Castro, L., Fairchild, G., Michaud, I., Osthus, D., Alaimo Di Loro, P., Maruotti, A., Eclerová, V., Kraus, A., Kraus, D., Pribylova, L., Dimitris, B., Li, M. L., Saksham, S., Dehning, J., Mohr, S., Priesemann, V., Redlarski, G., Bejar, B., Ardenghi, G., Parolini, N., Ziarelli, G., Bock, Wolfgang, Heyder, S., Hotz, T., E. Singh, D., Guzman-Merino, M., Aznarte, J. L., Moriña, D., Alonso, S., Alvarez, E., López, D., Prats, C., Burgard, J. P., Rodloff, A., Zimmermann, T., Kuhlmann, A., Zibert, J., Pennoni, F., Divino, F., Català, M., Lovison, G., Giudici, P., Tarantino, B., Bartolucci, F., Jona Lasinio, G., Mingione, M., Farcomeni, A., Srivastava, A., Montero-Manso, P., Adiga, A., Hurt, B., Lewis, B., Marathe, M., Porebski, P., Venkatramanan, S., Bartczuk, R., Dreger, F., Gambin, A., Gogolewski, K., Gruziel-S?omka, M., Krupa, B., Moszynski, A., Niedzielewski, K., Nowosielski, J., Radwan, M., Rakowski, F., Semeniuk, M., Szczurek, E., Zieli?ski, J., Kisielewski, J., Pabjan, B., Kheifetz, Y., Kirsten, H., Scholz, M., Biecek, P., Bodych, M., Filinski, M., Idzikowski, R., Krueger, T., Ozanski, T., Bracher, J., Funk, S., Sherratt, K., Gruson, H., Grah, R., Johnson, H., Niehus, R., Prasse, B., Sandmann, F., Deuschel, J., Wolffram, D., Abbott, S., Ullrich, A., Gibson, G., Ray, E. L., Reich, N. G., Sheldon, D., Wang, Y., Wattanachit, N., Wang, L., Trnka, J., Obozinski, G., Sun, T., Thanou, D., Pottier, L., Krymova, E., Meinke, J. H., Barbarossa, M. V., Leithäuser, N., Mohring, J., Schneider, J., Wlazlo, J., Fuhrmann, J., Lange, B., Rodiah, I., Baccam, P., Gurung, H., Stage, S., Suchoski, B., Budzinski, J., Walraven, R., Villanueva, I., Tucek, V., Smíd, M., Zajícek, M., Pérez Alvarez, C., Reina, B., Bosse, N. I., Meakin, S., Castro, L., Fairchild, G., Michaud, I., Osthus, D., Alaimo Di Loro, P., Maruotti, A., Eclerová, V., Kraus, A., Kraus, D., Pribylova, L., Dimitris, B., Li, M. L., Saksham, S., Dehning, J., Mohr, S., Priesemann, V., Redlarski, G., Bejar, B., Ardenghi, G., Parolini, N., Ziarelli, G., Bock, Wolfgang, Heyder, S., Hotz, T., E. Singh, D., Guzman-Merino, M., Aznarte, J. L., Moriña, D., Alonso, S., Alvarez, E., López, D., Prats, C., Burgard, J. P., Rodloff, A., Zimmermann, T., Kuhlmann, A., Zibert, J., Pennoni, F., Divino, F., Català, M., Lovison, G., Giudici, P., Tarantino, B., Bartolucci, F., Jona Lasinio, G., Mingione, M., Farcomeni, A., Srivastava, A., Montero-Manso, P., Adiga, A., Hurt, B., Lewis, B., Marathe, M., Porebski, P., Venkatramanan, S., Bartczuk, R., Dreger, F., Gambin, A., Gogolewski, K., Gruziel-S?omka, M., Krupa, B., Moszynski, A., Niedzielewski, K., Nowosielski, J., Radwan, M., Rakowski, F., Semeniuk, M., Szczurek, E., Zieli?ski, J., Kisielewski, J., Pabjan, B., Kheifetz, Y., Kirsten, H., Scholz, M., Biecek, P., Bodych, M., Filinski, M., Idzikowski, R., Krueger, T., Ozanski, T., Bracher, J., and Funk, S.

Abstract

Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance. Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast mod

Published
2023
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34. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.

Author

Domínguez, J., Boeree, M.J., Cambau, E., Chesov, D., Conradie, F., Cox, V., Dheda, K., Dudnyk, A., Farhat, M.R., Gagneux, S., Grobusch, M.P., Gröschel, M.I., Guglielmetti, L., Kontsevaya, I., Lange, B., Leth, F. van, Lienhardt, C., Mandalakas, A.M., Maurer, F.P., Merker, M., Miotto, P., Molina-Moya, B., Morel, F., Niemann, S., Veziris, N., Whitelaw, A., Horsburgh CR, J.r., Lange, C de, Domínguez, J., Boeree, M.J., Cambau, E., Chesov, D., Conradie, F., Cox, V., Dheda, K., Dudnyk, A., Farhat, M.R., Gagneux, S., Grobusch, M.P., Gröschel, M.I., Guglielmetti, L., Kontsevaya, I., Lange, B., Leth, F. van, Lienhardt, C., Mandalakas, A.M., Maurer, F.P., Merker, M., Miotto, P., Molina-Moya, B., Morel, F., Niemann, S., Veziris, N., Whitelaw, A., Horsburgh CR, J.r., and Lange, C de

Abstract

01 april 2023, Item does not contain fulltext, Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing. Review and the search for evidence included hand-searching journals and searching electronic databases. The panel identified studies that linked mutations in genomic regions of M tuberculosis with treatment outcome data. Implementation of molecular testing for the prediction of drug resistance in M tuberculosis is key. Detection of mutations in clinical isolates has implications for the clinical management of patients with multidrug-resistant or rifampicin-resistant tuberculosis, especially in situations when phenotypic drug susceptibility testing is not available. A multidisciplinary team including clinicians, microbiologists, and laboratory scientists reached a consensus on key questions relevant to molecular prediction of drug susceptibility or resistance to M tuberculosis, and their implications for clinical practice. This consensus document should help clinicians in the management of patients with tuberculosis, providing guidance for the design of treatment regimens and optimising outcomes.

Published
2023

37. TIBUSSII - the first triple beam single ion implantation setup for quantum applications

Author

(0000-0001-9539-5874) Klingner, N., (0000-0001-7192-716X) Hlawacek, G., (0000-0003-3698-3793) Facsko, S., Wedel, G., Grunze, S., Kirschke, T., Lange, B., Findeisen, S., Silvent, J., Delobbe, A., (0000-0001-9539-5874) Klingner, N., (0000-0001-7192-716X) Hlawacek, G., (0000-0003-3698-3793) Facsko, S., Wedel, G., Grunze, S., Kirschke, T., Lange, B., Findeisen, S., Silvent, J., and Delobbe, A.

Abstract

The ongoing miniaturization has reached a point where dopants, impurities or active impurities reach the quantum limit, making deterministic single ion implantation (SII) indispensable. Moreover, applications in quantum computing, spintronics, and magnonics require at the same time, a very precise spatial placement of these implants. Other requirements for such an implantation system would be a wide range of available ion species, the ability to implant at extremely low fluence as well as low voltage operation. Our new system, named Tibussii, is expected to address all of these requirements. It will be the first UHV system to include a liquid metal alloy ion source (LMAIS) focused ion beam (FIB) column, a plasma FIB, and a scanning electron microscope (SEM). The 4-nm SEM will be used for damage-free navigation, orientation and inspection. Both FIB columns are mass-separated columns with three Einzellenses, a chicane for neutral particles, and additional blankers and features optimized for single ion implantation. We will show the current status of the system, which is currently being installed and further developed by HZDR and Orsay Physics. To verify the implantation of single ions, we are currently developing a secondary electron (SE) detection system with a sensitivity close to unity. It will be based on a semiconductor detector and is expected to surpass the detection efficiency of existing systems based on electron multiplication, such as channeltrons or microchannel plates.

Published
2023

38. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations

Author

Sherratt, K, Gruson, H, Grah, R, Johnson, H, Niehus, R, Prasse, B, Sandmann, F, Deuschel, J, Wolffram, D, Abbott, S, Ullrich, A, Gibson, G, L Ray, E, G Reich, N, Sheldon, D, Wang, Y, Wattanachit, N, Wang, L, Trnka, J, Obozinski, G, Sun, T, Thanou, D, Pottier, L, Krymova, E, H Meinke, J, Vittoria Barbarossa, M, Leithäuser, N, Mohring, J, Schneider, J, Włazło, J, Fuhrmann, J, Lange, B, Rodiah, I, Baccam, P, Gurung, H, Stage, S, Suchoski, B, Budzinski, J, Walraven, R, Villanueva, I, Tucek, V, Smid, M, Zajíček, M, Pérez Álvarez, C, Reina, B, I Bosse, N, R Meakin, S, Castro, L, Fairchild, G, Michaud, I, Osthus, D, Alaimo Di Loro, P, Maruotti, A, Eclerová, V, Kraus, A, Kraus, D, Pribylova, L, Dimitris, B, Lingzhi Li, M, Saksham, S, Dehning, J, Mohr, S, Priesemann, V, Redlarski, G, Bejar, B, Ardenghi, G, Parolini, N, Ziarelli, G, Bock, W, Heyder, S, Hotz, T, E Singh, D, Guzman-Merino, M, L Aznarte, J, Moriña, D, Alonso, S, Álvarez, E, López, D, Prats, C, Pablo Burgard, J, Rodloff, A, Zimmermann, T, Kuhlmann, A, Zibert, J, Pennoni, F, Divino, F, Català, M, Lovison, G, Giudici, P, Tarantino, B, Bartolucci, F, Jona Lasinio, G, Mingione, M, Farcomeni, A, Srivastava, A, Montero-Manso, P, Adiga, A, Hurt, B, Lewis, B, Marathe, M, Porebski, P, Venkatramanan, S, P Bartczuk, R, Dreger, F, Gambin, A, Gogolewski, K, Gruziel-Słomka, M, Krupa, B, Moszyński, A, Niedzielewski, K, Nowosielski, J, Radwan, M, Rakowski, F, Semeniuk, M, Szczurek, E, Zieliński, J, Kisielewski, J, Pabjan, B, Kirsten, H, Kheifetz, Y, Scholz, M, Biecek, P, Bodych, M, Filinski, M, Idzikowski, R, Krueger, T, Ozanski, T, Bracher, J, Funk, S, Katharine Sherratt, Hugo Gruson, Rok Grah, Helen Johnson, Rene Niehus, Bastian Prasse, Frank Sandmann, Jannik Deuschel, Daniel Wolffram, Sam Abbott, Alexander Ullrich, Graham Gibson, Evan L Ray, Nicholas G Reich, Daniel Sheldon, Yijin Wang, Nutcha Wattanachit, Lijing Wang, Jan Trnka, Guillaume Obozinski, Tao Sun, Dorina Thanou, Loic Pottier, Ekaterina Krymova, Jan H Meinke, Maria Vittoria Barbarossa, Neele Leithäuser, Jan Mohring, Johanna Schneider, Jaroslaw Włazło, Jan Fuhrmann, Berit Lange, Isti Rodiah, Prasith Baccam, Heidi Gurung, Steven Stage, Bradley Suchoski, Jozef Budzinski, Robert Walraven, Inmaculada Villanueva, Vit Tucek, Martin Smid, Milan Zajíček, Cesar Pérez Álvarez, Borja Reina, Nikos I Bosse, Sophie R Meakin, Lauren Castro, Geoffrey Fairchild, Isaac Michaud, Dave Osthus, Pierfrancesco Alaimo Di Loro, Antonello Maruotti, Veronika Eclerová, Andrea Kraus, David Kraus, Lenka Pribylova, Bertsimas Dimitris, Michael Lingzhi Li, Soni Saksham, Jonas Dehning, Sebastian Mohr, Viola Priesemann, Grzegorz Redlarski, Benjamin Bejar, Giovanni Ardenghi, Nicola Parolini, Giovanni Ziarelli, Wolfgang Bock, Stefan Heyder, Thomas Hotz, David E Singh, Miguel Guzman-Merino, Jose L Aznarte, David Moriña, Sergio Alonso, Enric Álvarez, Daniel López, Clara Prats, Jan Pablo Burgard, Arne Rodloff, Tom Zimmermann, Alexander Kuhlmann, Janez Zibert, Fulvia Pennoni, Fabio Divino, Marti Català, Gianfranco Lovison, Paolo Giudici, Barbara Tarantino, Francesco Bartolucci, Giovanna Jona Lasinio, Marco Mingione, Alessio Farcomeni, Ajitesh Srivastava, Pablo Montero-Manso, Aniruddha Adiga, Benjamin Hurt, Bryan Lewis, Madhav Marathe, Przemyslaw Porebski, Srinivasan Venkatramanan, Rafal P Bartczuk, Filip Dreger, Anna Gambin, Krzysztof Gogolewski, Magdalena Gruziel-Słomka, Bartosz Krupa, Antoni Moszyński, Karol Niedzielewski, Jedrzej Nowosielski, Maciej Radwan, Franciszek Rakowski, Marcin Semeniuk, Ewa Szczurek, Jakub Zieliński, Jan Kisielewski, Barbara Pabjan, Holger Kirsten, Yuri Kheifetz, Markus Scholz, Przemyslaw Biecek, Marcin Bodych, Maciej Filinski, Radoslaw Idzikowski, Tyll Krueger, Tomasz Ozanski, Johannes Bracher, Sebastian Funk, Sherratt, K, Gruson, H, Grah, R, Johnson, H, Niehus, R, Prasse, B, Sandmann, F, Deuschel, J, Wolffram, D, Abbott, S, Ullrich, A, Gibson, G, L Ray, E, G Reich, N, Sheldon, D, Wang, Y, Wattanachit, N, Wang, L, Trnka, J, Obozinski, G, Sun, T, Thanou, D, Pottier, L, Krymova, E, H Meinke, J, Vittoria Barbarossa, M, Leithäuser, N, Mohring, J, Schneider, J, Włazło, J, Fuhrmann, J, Lange, B, Rodiah, I, Baccam, P, Gurung, H, Stage, S, Suchoski, B, Budzinski, J, Walraven, R, Villanueva, I, Tucek, V, Smid, M, Zajíček, M, Pérez Álvarez, C, Reina, B, I Bosse, N, R Meakin, S, Castro, L, Fairchild, G, Michaud, I, Osthus, D, Alaimo Di Loro, P, Maruotti, A, Eclerová, V, Kraus, A, Kraus, D, Pribylova, L, Dimitris, B, Lingzhi Li, M, Saksham, S, Dehning, J, Mohr, S, Priesemann, V, Redlarski, G, Bejar, B, Ardenghi, G, Parolini, N, Ziarelli, G, Bock, W, Heyder, S, Hotz, T, E Singh, D, Guzman-Merino, M, L Aznarte, J, Moriña, D, Alonso, S, Álvarez, E, López, D, Prats, C, Pablo Burgard, J, Rodloff, A, Zimmermann, T, Kuhlmann, A, Zibert, J, Pennoni, F, Divino, F, Català, M, Lovison, G, Giudici, P, Tarantino, B, Bartolucci, F, Jona Lasinio, G, Mingione, M, Farcomeni, A, Srivastava, A, Montero-Manso, P, Adiga, A, Hurt, B, Lewis, B, Marathe, M, Porebski, P, Venkatramanan, S, P Bartczuk, R, Dreger, F, Gambin, A, Gogolewski, K, Gruziel-Słomka, M, Krupa, B, Moszyński, A, Niedzielewski, K, Nowosielski, J, Radwan, M, Rakowski, F, Semeniuk, M, Szczurek, E, Zieliński, J, Kisielewski, J, Pabjan, B, Kirsten, H, Kheifetz, Y, Scholz, M, Biecek, P, Bodych, M, Filinski, M, Idzikowski, R, Krueger, T, Ozanski, T, Bracher, J, Funk, S, Katharine Sherratt, Hugo Gruson, Rok Grah, Helen Johnson, Rene Niehus, Bastian Prasse, Frank Sandmann, Jannik Deuschel, Daniel Wolffram, Sam Abbott, Alexander Ullrich, Graham Gibson, Evan L Ray, Nicholas G Reich, Daniel Sheldon, Yijin Wang, Nutcha Wattanachit, Lijing Wang, Jan Trnka, Guillaume Obozinski, Tao Sun, Dorina Thanou, Loic Pottier, Ekaterina Krymova, Jan H Meinke, Maria Vittoria Barbarossa, Neele Leithäuser, Jan Mohring, Johanna Schneider, Jaroslaw Włazło, Jan Fuhrmann, Berit Lange, Isti Rodiah, Prasith Baccam, Heidi Gurung, Steven Stage, Bradley Suchoski, Jozef Budzinski, Robert Walraven, Inmaculada Villanueva, Vit Tucek, Martin Smid, Milan Zajíček, Cesar Pérez Álvarez, Borja Reina, Nikos I Bosse, Sophie R Meakin, Lauren Castro, Geoffrey Fairchild, Isaac Michaud, Dave Osthus, Pierfrancesco Alaimo Di Loro, Antonello Maruotti, Veronika Eclerová, Andrea Kraus, David Kraus, Lenka Pribylova, Bertsimas Dimitris, Michael Lingzhi Li, Soni Saksham, Jonas Dehning, Sebastian Mohr, Viola Priesemann, Grzegorz Redlarski, Benjamin Bejar, Giovanni Ardenghi, Nicola Parolini, Giovanni Ziarelli, Wolfgang Bock, Stefan Heyder, Thomas Hotz, David E Singh, Miguel Guzman-Merino, Jose L Aznarte, David Moriña, Sergio Alonso, Enric Álvarez, Daniel López, Clara Prats, Jan Pablo Burgard, Arne Rodloff, Tom Zimmermann, Alexander Kuhlmann, Janez Zibert, Fulvia Pennoni, Fabio Divino, Marti Català, Gianfranco Lovison, Paolo Giudici, Barbara Tarantino, Francesco Bartolucci, Giovanna Jona Lasinio, Marco Mingione, Alessio Farcomeni, Ajitesh Srivastava, Pablo Montero-Manso, Aniruddha Adiga, Benjamin Hurt, Bryan Lewis, Madhav Marathe, Przemyslaw Porebski, Srinivasan Venkatramanan, Rafal P Bartczuk, Filip Dreger, Anna Gambin, Krzysztof Gogolewski, Magdalena Gruziel-Słomka, Bartosz Krupa, Antoni Moszyński, Karol Niedzielewski, Jedrzej Nowosielski, Maciej Radwan, Franciszek Rakowski, Marcin Semeniuk, Ewa Szczurek, Jakub Zieliński, Jan Kisielewski, Barbara Pabjan, Holger Kirsten, Yuri Kheifetz, Markus Scholz, Przemyslaw Biecek, Marcin Bodych, Maciej Filinski, Radoslaw Idzikowski, Tyll Krueger, Tomasz Ozanski, Johannes Bracher, and Sebastian Funk

Abstract

Background: Short-term forecasts of infectious disease contribute to situational awareness and capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise forecasts’ predictive performance by combining independent models into an ensemble. Here we report the performance of ensemble predictions of COVID-19 cases and deaths across Europe from March 2021 to March 2022. Methods: We created the European COVID-19 Forecast Hub, an online open-access platform where modellers upload weekly forecasts for 32 countries with results publicly visualised and evaluated. We created a weekly ensemble forecast from the equally-weighted average across individual models’ predictive quantiles. We measured forecast accuracy using a baseline and relative Weighted Interval Score (rWIS). We retrospectively explored ensemble methods, including weighting by past performance. Results: We collected weekly forecasts from 48 models, of which we evaluated 29 models alongside the ensemble model. The ensemble had a consistently strong performance across countries over time, performing better on rWIS than 91% of forecasts for deaths (N=763 predictions from 20 models), and 83% forecasts for cases (N=886 predictions from 23 models). Performance remained stable over a 4-week horizon for death forecasts but declined with longer horizons for cases. Among ensemble methods, the most influential choice came from using a median average instead of the mean, regardless of weighting component models. Conclusions: Our results support combining independent models into an ensemble forecast to improve epidemiological predictions, and suggest that median averages yield better performance than methods based on means. We highlight that forecast consumers should place more weight on incident death forecasts than case forecasts at horizons greater than two weeks. Funding: European Commission, Ministerio de Ciencia, Innovación y Universidades, FEDER; Ag

Published
2023

39. Characterization of a Unique Pair of Ferredoxin and Ferredoxin NADP + Reductase Isoforms That Operates in Non-Photosynthetic Glandular Trichomes.

Author

Polito, Joshua T., Lange, Iris, Barton, Kaylie E., Srividya, Narayanan, and Lange, B. Markus

Subjects
FERREDOXINS, MONOTERPENES, TRICHOMES, NICOTINAMIDE adenine dinucleotide phosphate, ELECTROPHILES, REDUCTION potential, PEPPERMINT, PHOTOREDUCTION
Abstract

Our recent investigations indicated that isoforms of ferredoxin (Fd) and ferredoxin NADP+ reductase (FNR) play essential roles for the reductive steps of the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway of terpenoid biosynthesis in peppermint glandular trichomes (GTs). Based on an analysis of several transcriptome data sets, we demonstrated the presence of transcripts for a leaf-type FNR (L-FNR), a leaf-type Fd (Fd I), a root-type FNR (R-FNR), and two root-type Fds (Fd II and Fd III) in several members of the mint family (Lamiaceae). The present study reports on the biochemical characterization of all Fd and FNR isoforms of peppermint (Mentha × piperita L.). The redox potentials of Fd and FNR isoforms were determined using photoreduction methods. Based on a diaphorase assay, peppermint R-FNR had a substantially higher specificity constant (kcat/Km) for NADPH than L-FNR. Similar results were obtained with ferricyanide as an electron acceptor. When assayed for NADPH–cytochrome c reductase activity, the specificity constant with the Fd II and Fd III isoforms (when compared to Fd I) was slightly higher for L-FNR and substantially higher for R-FNR. Based on real-time quantitative PCR assays with samples representing various peppermint organs and cell types, the Fd II gene was expressed very highly in metabolically active GTs (but also present at lower levels in roots), whereas Fd III was expressed at low levels in both roots and GTs. Our data provide evidence that high transcript levels of Fd II, and not differences in the biochemical properties of the encoded enzyme when compared to those of Fd III, are likely to support the formation of copious amounts of monoterpene via the MEP pathway in peppermint GTs. This work has laid the foundation for follow-up studies to further investigate the roles of a unique R-FNR–Fd II pair in non-photosynthetic GTs of the Lamiaceae. [ABSTRACT FROM AUTHOR]

Published
2024
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45. A framework for validating AI in precision medicine: considerations from the European ITFoC consortium

Author

Tsopra, R, Fernandez, X, Luchinat, C, Alberghina, L, Lehrach, H, Vanoni, M, Dreher, F, Sezerman, O, Cuggia, M, de Tayrac, M, Miklasevics, E, Itu, L, Geanta, M, Ogilvie, L, Godey, F, Boldisor, C, Campillo-Gimenez, B, Cioroboiu, C, Ciusdel, C, Coman, S, Hijano Cubelos, O, Itu, A, Lange, B, Le Gallo, M, Lespagnol, A, Mauri, G, Soykam, H, Rance, B, Turano, P, Tenori, L, Vignoli, A, Wierling, C, Benhabiles, N, Burgun, A, Tsopra R., Fernandez X., Luchinat C., Alberghina L., Lehrach H., Vanoni M., Dreher F., Sezerman O. U., Cuggia M., de Tayrac M., Miklasevics E., Itu L. M., Geanta M., Ogilvie L., Godey F., Boldisor C. N., Campillo-Gimenez B., Cioroboiu C., Ciusdel C. F., Coman S., Hijano Cubelos O., Itu A., Lange B., Le Gallo M., Lespagnol A., Mauri G., Soykam H. O., Rance B., Turano P., Tenori L., Vignoli A., Wierling C., Benhabiles N., Burgun A., Tsopra, R, Fernandez, X, Luchinat, C, Alberghina, L, Lehrach, H, Vanoni, M, Dreher, F, Sezerman, O, Cuggia, M, de Tayrac, M, Miklasevics, E, Itu, L, Geanta, M, Ogilvie, L, Godey, F, Boldisor, C, Campillo-Gimenez, B, Cioroboiu, C, Ciusdel, C, Coman, S, Hijano Cubelos, O, Itu, A, Lange, B, Le Gallo, M, Lespagnol, A, Mauri, G, Soykam, H, Rance, B, Turano, P, Tenori, L, Vignoli, A, Wierling, C, Benhabiles, N, Burgun, A, Tsopra R., Fernandez X., Luchinat C., Alberghina L., Lehrach H., Vanoni M., Dreher F., Sezerman O. U., Cuggia M., de Tayrac M., Miklasevics E., Itu L. M., Geanta M., Ogilvie L., Godey F., Boldisor C. N., Campillo-Gimenez B., Cioroboiu C., Ciusdel C. F., Coman S., Hijano Cubelos O., Itu A., Lange B., Le Gallo M., Lespagnol A., Mauri G., Soykam H. O., Rance B., Turano P., Tenori L., Vignoli A., Wierling C., Benhabiles N., and Burgun A.

Abstract

Background: Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods: The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results: This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions: The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

Published
2021

46. Preparing for future waves and pandemics: a global hospital survey on infection control measures and infection rates in COVID-19

Author

Matoori, S, Kuritzkes, D, Goh, Y, Quek, S, Wang, L, Sun, Z, di Marco, F, Borleri, D, Buoro, S, Fagiuoli, S, Ferrari, T, Rizzi, M, Raimondi, F, Cesa, S, Koh, D, Froehlich, J, Janssen, S, Lange, B, Egle, A, Erb, S, Mossdorf, E, Gutzeit, A, Matoori S., Kuritzkes D. R., Goh Y., Quek S. T., Wang L., Sun Z., di Marco F., Borleri D., Buoro S., Fagiuoli S., Ferrari T., Rizzi M., Raimondi F., Cesa S., Koh D. -M., Froehlich J. M., Janssen S., Lange B., Egle A., Erb S., Mossdorf E., Gutzeit A., Matoori, S, Kuritzkes, D, Goh, Y, Quek, S, Wang, L, Sun, Z, di Marco, F, Borleri, D, Buoro, S, Fagiuoli, S, Ferrari, T, Rizzi, M, Raimondi, F, Cesa, S, Koh, D, Froehlich, J, Janssen, S, Lange, B, Egle, A, Erb, S, Mossdorf, E, Gutzeit, A, Matoori S., Kuritzkes D. R., Goh Y., Quek S. T., Wang L., Sun Z., di Marco F., Borleri D., Buoro S., Fagiuoli S., Ferrari T., Rizzi M., Raimondi F., Cesa S., Koh D. -M., Froehlich J. M., Janssen S., Lange B., Egle A., Erb S., Mossdorf E., and Gutzeit A.

Abstract

A survey of hospitals on three continents was performed to assess their infection control preparedness and measures, and their infection rate in hospital health care workers during the COVID-19 pandemic. All surveyed hospitals used similar PPE but differences in preparedness, PPE shortages, and infection rates were reported.

Published
2021

47. Essays on partiality: special cases and new areas

Author

Lange, B, Bader, R, and Crisp, R

Subjects
Ethics, Philosophy
Abstract

The leitmotif of this thesis is the examination of special cases and new areas in the ethics of partiality. ‘Partiality’ refers to the special concern that we display for ourselves and other people with whom we stand in some special personal relationship. The first essay provides a thematic backdrop to the ethics of partiality. I trace the main themes in the debate on the ethics of partiality through a focus on permissible partiality (options) and required partiality (associative duties). The second essay considers one of the most special cases: the justification of parental partiality. I defend a new account of the right to parent that appeals to the special value of engaging in parental projects. These are a distinctive kind of valuable creative pursuit. The third essay extends the theme of permissible partiality, but with a twist. I defend the existence of what I call other-sacrificing options, which are permissions to act sub-optimally by making choices that discount the interests of people with whom we stand in an adversarial personal relationship. The fourth essay digs deeper into the question of what distinguishes pursuits that can justify permissible partiality from those that cannot. I develop a meaning-based view according to which those endeavours that can justify permissible partiality are meaningful. The fifth essay moves from the domain of permissible to the domain of required partiality. I explore the revisionist thesis that there can also be associative duties to give less moral priority to our adversaries. These duties turn out to be duties that we owe to ourselves. The sixth essay concludes by considering structural questions about the relationship between positive and negative partiality. Four symmetries between positive partiality to intimates and negative partiality to adversaries are defended. These, in turn, help point us to a more fundamental principle of morality: its propensity to dissolve negative personal relationships while preserving positive ones.

Published
2022

50. 847P Precision oncology for resistant acral, mucosal and cutaneous melanomas: A prospective broad high throughput genomics feasibility study

Author

Leyvraz, S., primary, Schütte, M., additional, Kessler, T., additional, Lamping, M., additional, Burock, S., additional, Ochsenreither, S., additional, Amstislavskiy, V., additional, Risch, T., additional, Jelas, I., additional, Ulrich, C., additional, Dobos, G., additional, Klauschen, F., additional, Schäfer, R., additional, Lange, B., additional, Klinghammer, K., additional, Yaspo, M-L., additional, and Keilholz, U., additional

Published
2022
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