Publications by authors named "Mario U Gaimann"

4 Publications

  • Page 1 of 1

Early life imprints the hierarchy of T cell clone sizes.

Elife 2020 12 21;9. Epub 2020 Dec 21.

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States.

The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, using mathematical modeling and statistical analyses of T cell receptor sequencing data, we develop a quantitative theory of human T cell dynamics compatible with the statistical laws of repertoire organization. We find that clonal expansions during a perinatal time window leave a long-lasting imprint on the human T cell repertoire, which is only slowly reshaped by fluctuating clonal selection during adult life. Our work provides a mechanism for how early clonal dynamics imprint the hierarchy of T cell clone sizes with implications for pathogen defense and autoimmunity.
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http://dx.doi.org/10.7554/eLife.61639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870140PMC
December 2020

Structural characterization of an ionic liquid in bulk and in nano-confined environment using data from MD simulations.

Data Brief 2020 Feb 23;28:104794. Epub 2019 Nov 23.

Group for Computational Life Sciences, Department of Physical Chemistry, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia.

This article contains data on structural characterization of the [C2Mim][NTf2] in bulk and in nano-confined environment obtained using MD simulations. These data supplement those presented in the paper "Insights from Molecular Dynamics Simulations on Structural Organization and Diffusive Dynamics of an Ionic Liquid at Solid and Vacuum Interfaces" [1], where force fields with three different charge methods and three charge scaling factors were used for the analysis of the IL in the bulk, at the interface with the vacuum and the IL film in the contact with a hydroxylated alumina surface. Here, we present details on the construction of the model systems in an extended detailed methods section. Furthermore, for best parametrization, structural and dynamic properties of IL in different environment are studied with certain features presented herein.
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http://dx.doi.org/10.1016/j.dib.2019.104794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909096PMC
February 2020

Observation of high-temperature macromolecular confinement in lyophilised protein formulations using terahertz spectroscopy.

Int J Pharm X 2019 Dec 8;1:100022. Epub 2019 Jul 8.

Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, United Kingdom.

Characterising the structural dynamics of proteins and the effects of excipients are critical for optimising the design of formulations. In this work we investigated four lyophilised formulations containing bovine serum albumin (BSA) and three formulations containing a monoclonal antibody (mAb, here mAb1), and explored the role of the excipients polysorbate 80, sucrose, trehalose, and arginine on stabilising proteins. By performing temperature variable terahertz time-domain spectroscopy (THz-TDS) experiments it is possible to study the vibrational dynamics of these formulations. The THz-TDS measurements reveal two distinct glass transition processes in all tested formulations. The lower temperature transition, , is associated with the onset of local motion due to the secondary relaxation whilst the higher temperature transition, , marks the onset of the -relaxation. For some of the formulations, containing globular BSA as well as mAb1, the absorption at terahertz frequencies does not increase further at temperatures above . Such behaviour is in contrast to our previous observations for small organic molecules as well as linear polymers where absorption is always observed to steadily increase with temperature due to the stronger absorption of terahertz radiation by more mobile dipoles. The absence of such further increase in absorption with higher temperatures therefore suggests a localised confinement of the protein/excipient matrix at high temperatures that hinders any further increase in mobility. We found that subtle changes in excipient composition had an effect on the transition temperatures and as well as the vibrational confinement in the solid state. Further work is required to establish the potential significance of the vibrational confinement in the solid state on formulation stability and chemical degradation as well as what role the excipients play in achieving such confinement.
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http://dx.doi.org/10.1016/j.ijpx.2019.100022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733290PMC
December 2019

Insights from molecular dynamics simulations on structural organization and diffusive dynamics of an ionic liquid at solid and vacuum interfaces.

J Colloid Interface Sci 2019 Oct 6;553:350-363. Epub 2019 Jun 6.

Group of Computational Life Sciences, Department of Physical Chemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia; PULS Group, Center for Nanostructured Films, Department of Physics, FAU Erlangen-Nürnberg, Cauerstraße 3, 91058, Erlangen, Germany. Electronic address:

Hypothesis: A reliable modelling approach is required for simultaneous characterisation of static and dynamic properties of bulk and interfacial ionic liquids (ILs). This is a prerequisite for a successful investigation of experimentally inaccessible, yet important properties, including those that change significantly with the distance from both vacuum and solid interfaces.

Simulations: We perform molecular dynamics simulations of bulk [CMim][NTf], and thick IL films in contact with vacuum and hydroxylated sapphire surface, using the charge methods CHelpG, RESP-HF and RESP-B3LYP with charge scaling factors 1.0, 0.9 and 0.85.

Findings: By determining and employing appropriate system sizes and simulations lengths, and by benchmarking against self-diffusion coefficients, surface tension, X-ray reflectivity, and structural data, we identify RESP-HF/0.9 as the best non-polarizable force field for this IL. We use this optimal parametrisation to predict novel physical properties of confined IL films. First we fully characterise the internal configurations and orientations of IL molecules relative to, and as a function of the distance from the solid and vacuum interfaces. Second, we evaluate densities together with mobilities in-plane and normal to the interfaces and find that strong correlations between the IL's stratification and diffusive transport in the interfacial layers persist for several nanometres deep into IL films.
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http://dx.doi.org/10.1016/j.jcis.2019.06.017DOI Listing
October 2019