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1701 Publications visible to you, out of a total of 1701
Improving DNA-Barcoding Databases: A Framework for Error Detection and Correction in the Barcode of Life Data System (BOLD)

Abstract

Not specified

Authors: Alexander Suhrkamp, Alexandros Stamatakis

Date Published: 1st Dec 2024

Publication Type: Master's Thesis

Digital-Tier Strategy Improves Newborn Screening for Glutaric Aciduria Type 1

Abstract (Expand)

Glutaric aciduria type 1 (GA1) is a rare inherited metabolic disease increasingly included in newborn screening (NBS) programs worldwide. Because of the broad biochemical spectrum of individuals with …dividuals with GA1 and the lack of reliable second-tier strategies, NBS for GA1 is still confronted with a high rate of false positives. In this study, we aim to increase the specificity of NBS for GA1 and, hence, to reduce the rate of false positives through machine learning methods. Therefore, we studied NBS profiles from 1,025,953 newborns screened between 2014 and 2023 at the Heidelberg NBS Laboratory, Germany. We identified a significant sex difference, resulting in twice as many false-positives male than female newborns. Moreover, the proposed digital-tier strategy based on logistic regression analysis, ridge regression, and support vector machine reduced the false-positive rate by over 90% compared to regular NBS while identifying all confirmed individuals with GA1 correctly. An in-depth analysis of the profiles revealed that in particular false-positive results with high associated follow-up costs could be reduced significantly. In conclusion, understanding the origin of false-positive NBS and implementing a digital-tier strategy to enhance the specificity of GA1 testing may significantly reduce the burden on newborns and their families from false-positive NBS results.

Authors: Elaine Zaunseder, Julian Teinert, Nikolas Boy, Sven F. Garbade, Saskia Haupt, Patrik Feyh, Georg F. Hoffmann, Stefan Kölker, Ulrike Mütze, Vincent Heuveline

Date Published: 1st Dec 2024

Publication Type: Journal

Dielectrophoretic force-enhanced thermal convection within a horizontal cylindrical annulus

Abstract (Expand)

This study investigates, both experimentally and numerically the flow of a dielectric fluid confined between two concentric, differentially heated, horizontally aligned cylinders subjected to a 200 Hz …ed to a 200 Hz alternating radial electric field. A wide-gap annular setup with a length 20 times larger than the gap size is utilized in this investigation. The study focuses exclusively on the outward heating configuration, meaning the inner cylinder is hotter than the outer one. The electric field, in conjunction with the temperature gradient, triggers thermal electro-hydrodynamic instability caused by the application of dielectrophoretic force. when the applied electric tension exceeds a critical value for specific temperature gradients between the cylinders, the flow symmetry in the gap is disturbed. The instability manifests as periodically oscillating vortices occurring on top of the gap. A notable increase in heat transfer efficiency accompanies the onset of instability. The experimental and numerical results demonstrate quantitative and qualitative agreement.

Authors: M. H. Hamede, J. Roller, A. Meyer, V. Heuveline, C. Egbers

Date Published: 1st Dec 2024

Publication Type: Journal

Dynamic whole-body models for infant metabolism

Abstract (Expand)

1 Abstract Comprehensive, sex-specific whole-body models (WBMs) accounting for organ-specific metabolism have been developed to allow for the simulation of adult and infant metabolism. These WBMs are …nfant metabolism. These WBMs are evaluated daily, giving insights into metabolic flux changes that occur in one day of an infant’s or adult’s life. However, for medical applications, such as in metabolic diseases and their treatment, an evaluation and concentration predictions on a shorter time scale would be beneficial. Therefore, we developed a dynamic infant-WBM that couples metabolite dynamics in short time frames through physiology-based pharma-cokinetic models with the existing infant whole-body models. We then tailored the dynamic infant-WBM enabling the prediction of isovalerylcarnitine (C5), a clinical biomarker used for the inherited metabolic disease isovaleric aciduria (IVA). Our results show that, as expected, the predicted C5 concentrations exceeded the newborn screening thresholds during the time (36 - 72 hours) newborn screening blood samples are taken in the IVA models but not in models simulating healthy infants. We also demonstrate how the dynamic infant-WBMs can be used to test the effect changes in dietary intake have on the biomarker. Since the dynamic infant-WBMs were parametrised with literature-derived experimental or estimated values, we show how uncertainty quantification can be applied to quantify the parameter uncertainties. We found that the fractional unbound plasma needed to be estimated correctly, as this parameter strongly impacted C5 concentration predictions of the dynamic infant-WBMs. Overall, the dynamic infant-WBMs hold promise for personalised medicine, as it enables personalised biomarker concentration predictions of healthy and diseased infant metabolism in various time intervals.

Authors: Elaine Zaunseder, Faiz Khan Mohammad, Ulrike Mütze, Stefan Kölker, Vincent Heuveline, Ines Thiele

Date Published: 26th Nov 2024

Publication Type: Journal

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models

Abstract (Expand)

BACKGROUND: The EF-hand Ca 2+ sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of …ancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca 2+ ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75–94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts. METHODS: We applied an integrative translational research pipeline ranging from in silico computational molecular modeling and in vitro biochemical molecular assays as well as isolated rodent and human cardiomyocyte performance assessments to in vivo safety and efficacy studies in small and large animal cardiac disease models. RESULTS: We characterize S100A1ct as a cell-penetrating peptide with positive inotropic and antiarrhythmic properties in normal and failing myocardium in vitro and in vivo. This activity translates into improved contractile performance and survival in preclinical heart failure models with reduced ejection fraction after S100A1ct systemic administration. S100A1ct exerts a fast and sustained dose-dependent enhancement of cardiomyocyte Ca 2+ cycling and prevents β-adrenergic receptor–triggered Ca 2+ imbalances by targeting SERCA2a and RyR2 activity. In line with the S100A1ct-mediated enhancement of SERCA2a activity, modeling suggests an interaction of the peptide with the transmembrane segments of the sarcoplasmic Ca 2+ pump. Incorporation of a cardiomyocyte-targeting peptide tag into S100A1ct (cor-S100A1ct) further enhanced its biological and therapeutic potency in vitro and in vivo. CONCLUSIONS: S100A1ct is a promising lead for the development of novel peptide-based therapeutics against heart failure with reduced ejection fraction.

Authors: Dorothea Kehr, Julia Ritterhoff, Manuel Glaser, Lukas Jarosch, Rafael E. Salazar, Kristin Spaich, Karl Varadi, Jennifer Birkenstock, Michael Egger, Erhe Gao, Walter J. Koch, Max Sauter, Marc Freichel, Hugo A. Katus, Norbert Frey, Andreas Jungmann, Cornelius Busch, Paul J. Mather, Arjang Ruhparwar, Martin Busch, Mirko Völkers, Rebecca C. Wade, Patrick Most

Date Published: 21st Nov 2024

Publication Type: Journal

KaMPIng: Flexible and (Near) Zero-Overhead C++ Bindings for MPI

Abstract (Expand)

The Message-Passing Interface (MPI) and C++ form the backbone of high-performance computing, but MPI only provides C and Fortran bindings. While this offers great language interoperability, high-level … programming languages like C++ make software development quicker and less error-prone.We propose novel C++language bindings that cover all abstraction levels from low-level MPI calls to convenient STL-style bindings, where most parameters are inferred from a small subset of parameters, by bringing named parameters to C++. This enables rapid prototyping and fine-tuning runtime behavior and memory management. A flexible type system and additional safety guarantees help to prevent programming errors.By exploiting C++’s template metaprogramming capabilities, this has (near) zero overhead, as only required code paths are generated at compile time.We demonstrate that our library is a strong foundation for a future distributed standard library using multiple application benchmarks, ranging from text-book sorting algorithms to phylogenetic interference.

Authors: Tim Niklas Uhl, Matthias Schimek, Lukas Hübner, Demian Hespe, Florian Kurpicz, Daniel Seemaier, Christoph Stelz, Peter Sanders

Date Published: 17th Nov 2024

Publication Type: Proceedings

Efficient Tree-based Parallel Algorithms for N-Body Simulations Using C++ Standard Parallelism

Abstract

Not specified

Authors: Thomas Lane Cassell, Tom Deakin, Aksel Alpay, Vincent Heuveline, Gonzalo Brito Gadeschi

Date Published: 17th Nov 2024

Publication Type: Journal

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