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  1. Book ; Thesis: Die Pankreatektomie mit Arterienresektion bei Pankreaskarzinom

    Kester, Tobias / Loos, Martin

    eine Analyse des perioperativen Outcomes

    2021  

    Institution Universität Heidelberg
    Author's details vorgelegt von Tobias Kester ; Doktorvater: Herr Priv.-Doz. Dr. med. Martin Loos
    Subject code 616.994 ; 610
    Language German
    Size 76 Seiten, Diagramme
    Publishing place Heidelberg
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Ruprecht-Karls-Universität Heidelberg, 2022
    HBZ-ID HT030351985
    Database Catalogue ZB MED Medicine, Health

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    2023 E 1208 order for loan Magazin

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  2. Article ; Online: Robust calibration of hierarchical population models for heterogeneous cell populations.

    Loos, Carolin / Hasenauer, Jan

    Journal of theoretical biology

    2019  Volume 488, Page(s) 110118

    Abstract: Cellular heterogeneity is known to have important effects on signal processing and cellular decision making. To understand these processes, multiple classes of mathematical models have been introduced. The hierarchical population model builds a novel ... ...

    Abstract Cellular heterogeneity is known to have important effects on signal processing and cellular decision making. To understand these processes, multiple classes of mathematical models have been introduced. The hierarchical population model builds a novel class which allows for the mechanistic description of heterogeneity and explicitly takes into account subpopulation structures. However, this model requires a parametric distribution assumption for the cell population and, so far, only the normal distribution has been employed. Here, we incorporate alternative distribution assumptions into the model, assess their robustness against outliers and evaluate their influence on the performance of model calibration in a simulation study and a real-world application example. We found that alternative distributions provide reliable parameter estimates even in the presence of outliers, and can in fact increase the convergence of model calibration.
    MeSH term(s) Calibration ; Computer Simulation ; Models, Statistical ; Models, Theoretical ; Normal Distribution
    Language English
    Publishing date 2019-12-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2019.110118
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  3. Article ; Online: Dissecting the antibody-OME: past, present, and future.

    Loos, Carolin / Lauffenburger, Douglas A / Alter, Galit

    Current opinion in immunology

    2020  Volume 65, Page(s) 89–96

    Abstract: Humoral immunity is key to protection for nearly all licensed vaccines. Yet, the design of vaccines has been more difficult for some of our most deadly killers (e.g. HIV, influenza, Dengue virus, etc.), likely due to our incomplete understanding of the ... ...

    Abstract Humoral immunity is key to protection for nearly all licensed vaccines. Yet, the design of vaccines has been more difficult for some of our most deadly killers (e.g. HIV, influenza, Dengue virus, etc.), likely due to our incomplete understanding of the precise immunological mechanisms associated with protection. Humoral immunity is governed both by B-cells and their bi-functional secreted antibodies, all of which have a unique capacity to evolve during an immune response. Current OMIC technologies capture individual features of the humoral immune response, providing a glimpse into humoral components (Fab/Fc/B-cell-omic), but fail to provide a wholistic view of the humoral response as a collective functional arm. Here, we dissect current OMIC strategies reviewing experimental and computational approaches, that if integrated could provide a true systems-level view of the humoral immune response.
    MeSH term(s) Animals ; Antibodies, Viral/immunology ; Humans ; Immunity, Humoral/immunology
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2020-08-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2020.06.003
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  4. Article ; Online: Comparison of null models for combination drug therapy reveals Hand model as biochemically most plausible.

    Sinzger, Mark / Vanhoefer, Jakob / Loos, Carolin / Hasenauer, Jan

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 3002

    Abstract: Null models for the effect of combination therapies are widely used to evaluate synergy and antagonism of drugs. Due to the relevance of null models, their suitability is continuously discussed. Here, we contribute to the discussion by investigating the ... ...

    Abstract Null models for the effect of combination therapies are widely used to evaluate synergy and antagonism of drugs. Due to the relevance of null models, their suitability is continuously discussed. Here, we contribute to the discussion by investigating the properties of five null models. Our study includes the model proposed by David J. Hand, which we refer to as Hand model. The Hand model has been introduced almost 20 years ago but hardly was used and studied. We show that the Hand model generalizes the principle of dose equivalence compared to the Loewe model and resolves the ambiguity of the Tallarida model. This provides a solution to the persisting conflict about the compatibility of two essential model properties: the sham combination principle and the principle of dose equivalence. By embedding several null models into a common framework, we shed light in their biochemical validity and provide indications that the Hand model is biochemically most plausible. We illustrate the practical implications and differences between null models by examining differences of null models on published data.
    MeSH term(s) Computer Simulation/standards ; Drug Interactions ; Drug Therapy, Combination/adverse effects ; Drug Therapy, Combination/methods ; Models, Theoretical
    Language English
    Publishing date 2019-02-28
    Publishing country England
    Document type Comparative Study ; Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-38907-x
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  5. Book ; Online: Mathematical modeling of variability in intracellular signaling

    Loos, Carolin / Hasenauer, Jan

    2019  

    Abstract: Cellular signaling is essential in information processing and decision making. Therefore, a variety of experimental approaches have been developed to study signaling on bulk and single-cell level. Single-cell measurements of signaling molecules ... ...

    Abstract Cellular signaling is essential in information processing and decision making. Therefore, a variety of experimental approaches have been developed to study signaling on bulk and single-cell level. Single-cell measurements of signaling molecules demonstrated a substantial cell-to-cell variability, raising questions about its causes and mechanisms and about how cell populations cope with or exploit cellular heterogeneity. To gain insights from single-cell signaling data, analysis and modeling approaches have been introduced. This review discusses these modeling approaches, with a focus on recent advances in the development and calibration of mechanistic models. Additionally, it outlines current and future challenges.
    Keywords Quantitative Biology - Quantitative Methods
    Publishing date 2019-04-17
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Systems serology-based comparison of antibody effector functions induced by adjuvanted vaccines to guide vaccine design.

    Loos, Carolin / Coccia, Margherita / Didierlaurent, Arnaud M / Essaghir, Ahmed / Fallon, Jonathan K / Lauffenburger, Douglas / Luedemann, Corinne / Michell, Ashlin / van der Most, Robbert / Zhu, Alex Lee / Alter, Galit / Burny, Wivine

    NPJ vaccines

    2023  Volume 8, Issue 1, Page(s) 34

    Abstract: The mechanisms by which antibodies confer protection vary across vaccines, ranging from simple neutralization to functions requiring innate immune recruitment via Fc-dependent mechanisms. The role of adjuvants in shaping the maturation of antibody- ... ...

    Abstract The mechanisms by which antibodies confer protection vary across vaccines, ranging from simple neutralization to functions requiring innate immune recruitment via Fc-dependent mechanisms. The role of adjuvants in shaping the maturation of antibody-effector functions remains under investigated. Using systems serology, we compared adjuvants in licensed vaccines (AS01
    Language English
    Publishing date 2023-03-08
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-023-00613-1
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  7. Article ; Online: Comparison of null models for combination drug therapy reveals Hand model as biochemically most plausible

    Mark Sinzger / Jakob Vanhoefer / Carolin Loos / Jan Hasenauer

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 15

    Abstract: Abstract Null models for the effect of combination therapies are widely used to evaluate synergy and antagonism of drugs. Due to the relevance of null models, their suitability is continuously discussed. Here, we contribute to the discussion by ... ...

    Abstract Abstract Null models for the effect of combination therapies are widely used to evaluate synergy and antagonism of drugs. Due to the relevance of null models, their suitability is continuously discussed. Here, we contribute to the discussion by investigating the properties of five null models. Our study includes the model proposed by David J. Hand, which we refer to as Hand model. The Hand model has been introduced almost 20 years ago but hardly was used and studied. We show that the Hand model generalizes the principle of dose equivalence compared to the Loewe model and resolves the ambiguity of the Tallarida model. This provides a solution to the persisting conflict about the compatibility of two essential model properties: the sham combination principle and the principle of dose equivalence. By embedding several null models into a common framework, we shed light in their biochemical validity and provide indications that the Hand model is biochemically most plausible. We illustrate the practical implications and differences between null models by examining differences of null models on published data.
    Keywords Medicine ; R ; Science ; Q
    Subject code 006
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Scalable Inference of Ordinary Differential Equation Models of Biochemical Processes.

    Fröhlich, Fabian / Loos, Carolin / Hasenauer, Jan

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1883, Page(s) 385–422

    Abstract: Ordinary differential equation models have become a standard tool for the mechanistic description of biochemical processes. If parameters are inferred from experimental data, such mechanistic models can provide accurate predictions about the behavior of ... ...

    Abstract Ordinary differential equation models have become a standard tool for the mechanistic description of biochemical processes. If parameters are inferred from experimental data, such mechanistic models can provide accurate predictions about the behavior of latent variables or the process under new experimental conditions. Complementarily, inference of model structure can be used to identify the most plausible model structure from a set of candidates, and, thus, gain novel biological insight. Several toolboxes can infer model parameters and structure for small- to medium-scale mechanistic models out of the box. However, models for highly multiplexed datasets can require hundreds to thousands of state variables and parameters. For the analysis of such large-scale models, most algorithms require intractably high computation times. This chapter provides an overview of the state-of-the-art methods for parameter and model inference, with an emphasis on scalability.
    MeSH term(s) Algorithms ; Biochemical Phenomena ; Data Interpretation, Statistical ; Datasets as Topic ; Models, Biological ; Systems Biology/instrumentation ; Systems Biology/methods
    Language English
    Publishing date 2018-12-13
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-8882-2_16
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Hierarchical optimization for the efficient parametrization of ODE models.

    Loos, Carolin / Krause, Sabrina / Hasenauer, Jan

    Bioinformatics (Oxford, England)

    2018  Volume 34, Issue 24, Page(s) 4266–4273

    Abstract: Motivation: Mathematical models are nowadays important tools for analyzing dynamics of cellular processes. The unknown model parameters are usually estimated from experimental data. These data often only provide information about the relative changes ... ...

    Abstract Motivation: Mathematical models are nowadays important tools for analyzing dynamics of cellular processes. The unknown model parameters are usually estimated from experimental data. These data often only provide information about the relative changes between conditions, hence, the observables contain scaling parameters. The unknown scaling parameters and corresponding noise parameters have to be inferred along with the dynamic parameters. The nuisance parameters often increase the dimensionality of the estimation problem substantially and cause convergence problems.
    Results: In this manuscript, we propose a hierarchical optimization approach for estimating the parameters for ordinary differential equation (ODE) models from relative data. Our approach restructures the optimization problem into an inner and outer subproblem. These subproblems possess lower dimensions than the original optimization problem, and the inner problem can be solved analytically. We evaluated accuracy, robustness and computational efficiency of the hierarchical approach by studying three signaling pathways. The proposed approach achieved better convergence than the standard approach and required a lower computation time. As the hierarchical optimization approach is widely applicable, it provides a powerful alternative to established approaches.
    Availability and implementation: The code is included in the MATLAB toolbox PESTO which is available at http://github.com/ICB-DCM/PESTO.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Computational Biology/methods ; Models, Biological ; Signal Transduction ; Software/standards
    Language English
    Publishing date 2018-07-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/bty514
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  10. Article ; Online: Hierarchical optimization for the efficient parametrization of ODE models

    Loos, Carolin / Krause, Sabrina / Hasenauer, Jan

    Bioinformatics. 2018 Dec. 15, v. 34, no. 24, p. 4266-4273

    2018  , Page(s) 4266–4273

    Abstract: Mathematical models are nowadays important tools for analyzing dynamics of cellular processes. The unknown model parameters are usually estimated from experimental data. These data often only provide information about the relative changes between ... ...

    Abstract Mathematical models are nowadays important tools for analyzing dynamics of cellular processes. The unknown model parameters are usually estimated from experimental data. These data often only provide information about the relative changes between conditions, hence, the observables contain scaling parameters. The unknown scaling parameters and corresponding noise parameters have to be inferred along with the dynamic parameters. The nuisance parameters often increase the dimensionality of the estimation problem substantially and cause convergence problems. In this manuscript, we propose a hierarchical optimization approach for estimating the parameters for ordinary differential equation (ODE) models from relative data. Our approach restructures the optimization problem into an inner and outer subproblem. These subproblems possess lower dimensions than the original optimization problem, and the inner problem can be solved analytically. We evaluated accuracy, robustness and computational efficiency of the hierarchical approach by studying three signaling pathways. The proposed approach achieved better convergence than the standard approach and required a lower computation time. As the hierarchical optimization approach is widely applicable, it provides a powerful alternative to established approaches. The code is included in the MATLAB toolbox PESTO which is available at http://github.com/ICB-DCM/PESTO Supplementary data are available at Bioinformatics online.
    Keywords bioinformatics ; differential equation ; system optimization
    Language English
    Dates of publication 2018-1215
    Size p. 4266-4273
    Publishing place Oxford University Press
    Document type Article ; Online
    Note NAL-AP-2-clean ; Use and reproduction
    ZDB-ID 1468345-3
    ISSN 1367-4811 ; 1460-2059
    ISSN 1367-4811 ; 1460-2059
    DOI 10.1093/bioinformatics/bty514
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