Publications by authors named "Lukas Zimmermann"

11 Publications

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An MR-only acquisition and artificial intelligence based image-processing protocol for photon and proton therapy using a low field MR.

Z Med Phys 2021 Feb 15;31(1):78-88. Epub 2021 Jan 15.

Division of Medical Radiation Physics, Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Objective: Recent developments on synthetically generated CTs (sCT), hybrid MRI linacs and MR-only simulations underlined the clinical feasibility and acceptance of MR guided radiation therapy. However, considering clinical application of open and low field MR with a limited field of view can result in truncation of the patient's anatomy which further affects the MR to sCT conversion. In this study an acquisition protocol and subsequent MR image stitching is proposed to overcome the limited field of view restriction of open MR scanners, for MR-only photon and proton therapy.

Material And Methods: 12 prostate cancer patients scanned with an open 0.35T scanner were included. To obtain the full body contour an enhanced imaging protocol including two repeated scans after bilateral table movement was introduced. All required structures (patient contour, target and organ at risk) were delineated on a post-processed combined transversal image set (stitched MRI). The postprocessed MR was converted into a sCT by a pretrained neural network generator. Inversely planned photon and proton plans (VMAT and SFUD) were designed using the sCT and recalculated for rigidly and deformably registered CT images and compared based on D2%, D50%, V70Gy for organs at risk and based on D2%, D50%, D98% for the CTV and PTV. The stitched MRI and the untruncated MRI were compared to the CT, and the maximum surface distance was calculated. The sCT was evaluated with respect to delineation accuracy by comparing on stitched MRI and sCT using the DICE coefficient for femoral bones and the whole body.

Results: Maximum surface distance analysis revealed uncertainties in lateral direction of 1-3mm on average. DICE coefficient analysis confirms good performance of the sCT conversion, i.e. 92%, 93%, and 100% were obtained for femoral bone left and right and whole body. Dose comparison resulted in uncertainties below 1% between deformed CT and sCT and below 2% between rigidly registered CT and sCT in the CTV for photon and proton treatment plans.

Discussion: A newly developed acquisition protocol for open MR scanners and subsequent Sct generation revealed good acceptance for photon and proton therapy. Moreover, this protocol tackles the restriction of the limited FOVs and expands the capacities towards MR guided proton therapy with horizontal beam lines.
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http://dx.doi.org/10.1016/j.zemedi.2020.10.004DOI Listing
February 2021

MR-guided proton therapy: Impact of magnetic fields on the detector response.

Med Phys 2021 May 3;48(5):2572-2579. Epub 2021 Apr 3.

Division of Medical Physics, Department of Radiation Oncology, Medical University of Vienna, 1090, Vienna, Austria.

Purpose: To investigate the response of detectors for proton dosimetry in the presence of magnetic fields.

Material And Methods: Four ionization chambers (ICs), two thimble-type and two plane-parallel-type, and a diamond detector were investigated. All detectors were irradiated with homogeneous single-energy-layer fields, using 252.7 MeV proton beams. A Farmer IC was additionally irradiated in the same geometrical configuration, but with a lower nominal energy of 97.4 MeV. The beams were subjected to magnetic field strengths of 0, 0.25, 0.5, 0.75, and 1 T produced by a research dipole magnet placed at the room's isocenter. Detectors were positioned at 2 cm water equivalent depth, with their stem perpendicular to both the magnetic field lines and the proton beam's central axis, in the direction of the Lorentz force. Normality and two sample statistical Student's t tests were performed to assess the influence of the magnetic field on the detectors' responses.

Results: For all detectors, a small but significant magnetic field-dependent change of their response was found. Observed differences compared to the no magnetic field case ranged from +0.5% to -0.7%. The magnetic field dependence was found to be nonlinear and highest between 0.25 and 0.5 T for 252.7 MeV proton beams. A different variation of the Farmer chamber response with magnetic field strength was observed for irradiations using lower energy (97.4 MeV) protons. The largest magnetic field effects were observed for plane-parallel ionization chambers.

Conclusion: Small magnetic field-dependent changes in the detector response were identified, which should be corrected for dosimetric applications.
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http://dx.doi.org/10.1002/mp.14660DOI Listing
May 2021

Hybrid low-voltage physical unclonable function based on inkjet-printed metal-oxide transistors.

Nat Commun 2020 Nov 2;11(1):5543. Epub 2020 Nov 2.

Institute of Nanotechnology, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, Eggenstein-Leopoldshafen, 76344, Germany.

Modern society is striving for digital connectivity that demands information security. As an emerging technology, printed electronics is a key enabler for novel device types with free form factors, customizability, and the potential for large-area fabrication while being seamlessly integrated into our everyday environment. At present, information security is mainly based on software algorithms that use pseudo random numbers. In this regard, hardware-intrinsic security primitives, such as physical unclonable functions, are very promising to provide inherent security features comparable to biometrical data. Device-specific, random intrinsic variations are exploited to generate unique secure identifiers. Here, we introduce a hybrid physical unclonable function, combining silicon and printed electronics technologies, based on metal oxide thin film devices. Our system exploits the inherent randomness of printed materials due to surface roughness, film morphology and the resulting electrical characteristics. The security primitive provides high intrinsic variation, is non-volatile, scalable and exhibits nearly ideal uniqueness.
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http://dx.doi.org/10.1038/s41467-020-19324-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608659PMC
November 2020

OpenPepXL: An Open-Source Tool for Sensitive Identification of Cross-Linked Peptides in XL-MS.

Mol Cell Proteomics 2020 12 16;19(12):2157-2168. Epub 2020 Oct 16.

Biomolecular Interactions, Max Planck Institute for Developmental Biology, Tübingen, Germany; Institute for Bioinformatics and Medical Informatics, University of Tübingen, Tübingen, Germany; Applied Bioinformatics, Dept. of Computer Science, University of Tübingen, Tübingen, Germany; Institute for Translational Bioinformatics, University Hospital Tübingen, Tübingen, Germany; Quantitative Biology Center, University of Tübingen, Tübingen, Germany. Electronic address:

Cross-linking MS (XL-MS) has been recognized as an effective source of information about protein structures and interactions. In contrast to regular peptide identification, XL-MS has to deal with a quadratic search space, where peptides from every protein could potentially be cross-linked to any other protein. To cope with this search space, most tools apply different heuristics for search space reduction. We introduce a new open-source XL-MS database search algorithm, OpenPepXL, which offers increased sensitivity compared with other tools. OpenPepXL searches the full search space of an XL-MS experiment without using heuristics to reduce it. Because of efficient data structures and built-in parallelization OpenPepXL achieves excellent runtimes and can also be deployed on large compute clusters and cloud services while maintaining a slim memory footprint. We compared OpenPepXL to several other commonly used tools for identification of noncleavable labeled and label-free cross-linkers on a diverse set of XL-MS experiments. In our first comparison, we used a data set from a fraction of a cell lysate with a protein database of 128 targets and 128 decoys. At 5% FDR, OpenPepXL finds from 7% to over 50% more unique residue pairs (URPs) than other tools. On data sets with available high-resolution structures for cross-link validation OpenPepXL reports from 7% to over 40% more structurally validated URPs than other tools. Additionally, we used a synthetic peptide data set that allows objective validation of cross-links without relying on structural information and found that OpenPepXL reports at least 12% more validated URPs than other tools. It has been built as part of the OpenMS suite of tools and supports Windows, macOS, and Linux operating systems. OpenPepXL also supports the MzIdentML 1.2 format for XL-MS identification results. It is freely available under a three-clause BSD license at https://openms.org/openpepxl.
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http://dx.doi.org/10.1074/mcp.TIR120.002186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710140PMC
December 2020

The natural course of urinalysis after urinary diversion.

World J Urol 2021 May 13;39(5):1559-1567. Epub 2020 Jul 13.

Department of Urology, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Objective: To evaluate the impact of urinary diversion on regular features of urinalysis and to screen for risk factors of infection-related complications.

Methods: We conducted a retrospective, single-centre study of 429 patients who underwent open radical cystectomy. Patients were followed for 12 months and data of the complete urinalyses were analysed at three pre-defined time points.

Results: Two weeks after surgery, dipstick testing with positive reactions for leukocyte esterase and haemoglobin were confirmed in 80.7% and 80% after ileal conduit (IC) and orthotopic ileal neobladder (NB), respectively. Every patient was positive for these parameters 12 months after surgery. Correspondingly, the microscopic examination detected leukocytes (84% vs. 85.4%), erythrocytes (82.8% vs. 83.8%) and bacteria (94.3% vs. 96.8%) following IC and NB reconstruction. After 12 months, all parameters were positive irrespective of the type of urinary diversion. Two weeks after surgery positive urine cultures were obtained in more than 50% of cases after IC (52.5%) and NB (60.5%) (p > 0.05). All urine cultures were positive after 12 months with significantly more poly-microbial results found after NB (81.3%) compared with IC (67.2%) (p = 0.018). In univariate and multivariate logistic regression analysis the presence of hydronephrosis was independently associated with the occurrence of infectious complications (OR 4.2; CI 95% 1.525-11.569; p = 0.006).

Conclusion: A positive urinalysis is a common finding after urinary diversion. Hydronephrosis is a serious risk factor with respect to infection-related complications. The simple fact of a positive urinalysis does not warrant antimicrobial treatment.
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http://dx.doi.org/10.1007/s00345-020-03355-0DOI Listing
May 2021

Enabling ad-hoc reuse of private data repositories through schema extraction.

J Biomed Semantics 2020 07 8;11(1). Epub 2020 Jul 8.

Informatik 5, RWTH Aachen University, Ahornstr. 55, Aachen, 52062, Germany.

Background: Sharing sensitive data across organizational boundaries is often significantly limited by legal and ethical restrictions. Regulations such as the EU General Data Protection Rules (GDPR) impose strict requirements concerning the protection of personal and privacy sensitive data. Therefore new approaches, such as the Personal Health Train initiative, are emerging to utilize data right in their original repositories, circumventing the need to transfer data.

Results: Circumventing limitations of previous systems, this paper proposes a configurable and automated schema extraction and publishing approach, which enables ad-hoc SPARQL query formulation against RDF triple stores without requiring direct access to the private data. The approach is compatible with existing Semantic Web-based technologies and allows for the subsequent execution of such queries in a safe setting under the data provider's control. Evaluation with four distinct datasets shows that a configurable amount of concise and task-relevant schema, closely describing the structure of the underlying data, was derived, enabling the schema introspection-assisted authoring of SPARQL queries.

Conclusions: Automatically extracting and publishing data schema can enable the introspection-assisted creation of data selection and integration queries. In conjunction with the presented system architecture, this approach can enable reuse of data from private repositories and in settings where agreeing upon a shared schema and encoding a priori is infeasible. As such, it could provide an important step towards reuse of data from previously inaccessible sources and thus towards the proliferation of data-driven methods in the biomedical domain.
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http://dx.doi.org/10.1186/s13326-020-00223-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341611PMC
July 2020

ClinVAP: a reporting strategy from variants to therapeutic options.

Bioinformatics 2020 04;36(7):2316-2317

Department of Computer Science, Applied Bioinformatics, Tübingen 72076, Germany.

Motivation: Next-generation sequencing has become routine in oncology and opens up new avenues of therapies, particularly in personalized oncology setting. An increasing number of cases also implies a need for a more robust, automated and reproducible processing of long lists of variants for cancer diagnosis and therapy. While solutions for the large-scale analysis of somatic variants have been implemented, existing solutions often have issues with reproducibility, scalability and interoperability.

Results: Clinical Variant Annotation Pipeline (ClinVAP) is an automated pipeline which annotates, filters and prioritizes somatic single nucleotide variants provided in variant call format. It augments the variant information with documented or predicted clinical effect. These annotated variants are prioritized based on driver gene status and druggability. ClinVAP is available as a fully containerized, self-contained pipeline maximizing reproducibility and scalability allowing the analysis of larger scale data. The resulting JSON-based report is suited for automated downstream processing, but ClinVAP can also automatically render the information into a user-defined template to yield a human-readable report.

Availability And Implementation: ClinVAP is available at https://github.com/PersonalizedOncology/ClinVAP.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btz924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141851PMC
April 2020

A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core.

J Mol Biol 2018 07 16;430(15):2237-2243. Epub 2017 Dec 16.

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen D-72076, Germany. Electronic address:

The MPI Bioinformatics Toolkit (https://toolkit.tuebingen.mpg.de) is a free, one-stop web service for protein bioinformatic analysis. It currently offers 34 interconnected external and in-house tools, whose functionality covers sequence similarity searching, alignment construction, detection of sequence features, structure prediction, and sequence classification. This breadth has made the Toolkit an important resource for experimental biology and for teaching bioinformatic inquiry. Recently, we replaced the first version of the Toolkit, which was released in 2005 and had served around 2.5 million queries, with an entirely new version, focusing on improved features for the comprehensive analysis of proteins, as well as on promoting teaching. For instance, our popular remote homology detection server, HHpred, now allows pairwise comparison of two sequences or alignments and offers additional profile HMMs for several model organisms and domain databases. Here, we introduce the new version of our Toolkit and its application to the analysis of proteins.
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http://dx.doi.org/10.1016/j.jmb.2017.12.007DOI Listing
July 2018

[Modalities of acupuncture treatments in assisted reproductive technology--a comparison of treatment practice in Swiss, German, and Austrian fertility centers with findings from randomized controlled trials].

Forsch Komplementmed 2013 12;20(2):112-8. Epub 2013 Apr 12.

Universität Bern, Kollegiale Instanz für Komplementärmedizin KIKOM, Bern, Schweiz.

Background: One in 5 couples is affected by infertility. To increase the effectiveness of assisted reproductive technology (ART) adjuvant acupuncture treatments are frequently administered. However, little is known about acupuncture treatment modalities employed in fertility centers. The aim of our study was to assess modalities of acupuncture treatments in fertility centers and compare them with investigated acupuncture treatments in randomized controlled trials (RCTs) related to ART.

Methods: Referring to fertility centers listed on the websites of the Swiss, German, and Austrian national fertility associations, 180 centers were invited to participate in an online survey assessing the provision of acupuncture in ART. Survey results were compared with data from 17 RCTs.

Results: Acupuncture was offered by 33 (38.4%) of all responding fertility centers (n = 86; responder rate = 47.8%). In 39.4% the selection of acupuncture points is standardized or semi-standardized (24.2%) and in 27.3% based on individual TCM-diagnosis. Body acupuncture using needle stimulation was mentioned most frequently (84.8%). Some clinics reported additional use of auricular acupuncture (24.2%) and moxibustion (21.2%). Treatment providers were mainly physician-acupuncturists (84.8%). Compared to the RCTs, we found strong differences in point selection, mode of stimulation, and professional background of treatment providers.

Conclusions: Less than 40% of all fertility centres in Switzerland, Germany, and Austria offering acupuncture employ standardized acupuncture treatment protocols. To increase external validity of acupuncture research in ART, and to investigate clinical effectiveness of this adjuvant intervention, semi-standardized and individualized point selection should be considered, and treatment provision by non-acupuncturists should be omitted in future trials.
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http://dx.doi.org/10.1159/000350717DOI Listing
February 2014

Mast fruiting of large ectomycorrhizal African rain forest trees: importance of dry season intensity, and the resource-limitation hypothesis.

New Phytol 2006 ;170(3):561-79

Institute of Plant Sciences, University of Bern, Altenbergrain 21, CH-3013 Bern, Switzerland.

Mast fruiting is a distinctive reproductive trait in trees. This rain forest study, at a nutrient-poor site with a seasonal climate in tropical Africa, provides new insights into the causes of this mode of phenological patterning. At Korup, Cameroon, 150 trees of the large, ectomycorrhizal caesalp, Microberlinia bisulcata, were recorded almost monthly for leafing, flowering and fruiting during 1995-2000. The series was extended to 1988-2004 with less detailed data. Individual transitions in phenology were analysed. Masting occurred when the dry season before fruiting was drier, and the one before that was wetter, than average. Intervals between events were usually 2 or 3 yr. Masting was associated with early leaf exchange, followed by mass flowering, and was highly synchronous in the population. Trees at higher elevation showed more fruiting. Output declined between 1995 and 2000. Mast fruiting in M. bisulcata appears to be driven by climate variation and is regulated by internal tree processes. The resource-limitation hypothesis was supported. An 'alternative bearing' system seems to underlie masting. That ectomycorrhizal habit facilitates masting in trees is strongly implied.
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http://dx.doi.org/10.1111/j.1469-8137.2006.01691.xDOI Listing
June 2006

Intra-annual radial growth and water relations of trees: implications towards a growth mechanism.

J Exp Bot 2006 23;57(6):1445-59. Epub 2006 Mar 23.

Institute of Plant Sciences, University of Bern, Altenbergrain 21, CH-3013 Bern, Switzerland.

There is a missing link between tree physiological and wood-anatomical knowledge which makes it impossible mechanistically to explain and predict the radial growth of individual trees from climate data. Empirical data of microclimatic factors, intra-annual growth rates, and tree-specific ratios between actual and potential transpiration (T PET(-1)) of trees of three species (Quercus pubescens, Pinus sylvestris, and Picea abies) at two dry sites in the central Wallis, Switzerland, were recorded from 2002 to 2004 at a 10 min resolution. This included the exceptionally hot and dry summer of 2003. These data were analysed in terms of direct (current conditions) and indirect impacts (predispositions of the past year) on growth. Rain was found to be the only factor which, to a large extent, consistently explained the radial increment for all three tree species at both sites and in the short term as well. Other factors had some explanatory power on the seasonal time-scale only. Quercus pubescens built up much of its tree ring before bud break. Pinus sylvestris and Picea abies started radial growth 1-2 weeks after Quercus pubescens and this was despite the fact that they had a high T PET(-1) before budburst and radial growth started. A high T PET(-1) was assumed to be related to open stomata, a very high net CO2 assimilation rate, and thus a potential carbon (C)-income for the tree. The main period of radial growth covered about 30-70% of the productive days of a year. In terms of C-allocation, these results mean that Quercus pubescens depended entirely on internal C-stores in the early phase of radial growth and that for all three species there was a long time period of C-assimilation which was not used for radial growth in above-ground wood. The results further suggest a strong dependence of radial growth on the current tree water relations and only secondarily on the C-balance. A concept is discussed which links radial growth over a feedback loop to actual tree water-relations and long-term affected C-storage to microclimate.
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http://dx.doi.org/10.1093/jxb/erj125DOI Listing
August 2006