Comparison of free-surface and conservative Allen-Cahn phase-field lattice Boltzmann method

This study compares the free-surface lattice Boltzmann method (FSLBM) with the conservative Allen-Cahn phase-field lattice Boltzmann method (PFLBM) in their ability to model two-phase flows in which the behavior of the system is dominated by the heavy phase. Both models are introduced and their individual properties, strengths and weaknesses are thoroughly discussed. Six numerical benchmark cases were simulated with both models, including (i) a standing gravity and (ii) capillary wave, (iii) an unconfined rising gas bubble in liquid, (iv) a Taylor bubble in a cylindrical tube, and (v) the vertical and (vi) oblique impact of a drop into a pool of liquid. Comparing the simulation results with either analytical models or experimental data from the literature, four major observations were made. Firstly, the PFLBM selected was able to simulate flows purely governed by surface tension with reasonable accuracy. Secondly, the FSLBM, a sharp interface model, generally requires a lower resolution than the PFLBM, a diffuse interface model. However, in the limit case of a standing wave, this was not observed. Thirdly, in simulations of a bubble moving in a liquid, the FSLBM accurately predicted the bubble's shape and rise velocity with low computational resolution. Finally, the PFLBM's accuracy is found to be sensitive to the choice of the model's mobility parameter and interface width

The Complexity of Cluster Vertex Splitting and Company

Clustering a graph when the clusters can overlap can be seen from three different angles: We may look for cliques that cover the edges of the graph, we may look to add or delete few edges to uncover the cluster structure, or we may split vertices to separate the clusters from each other. Splitting a vertex $v$ means to remove it and to add two new copies of $v$ and to make each previous neighbor of $v$ adjacent with at least one of the copies. In this work, we study the underlying computational problems regarding the three angles to overlapping clusterings, in particular when the overlap is small. We show that the above-mentioned covering problem, which also has been independently studied in different contexts,is NP-complete. Based on a previous so-called critical-clique lemma, we leverage our hardness result to show that Cluster Editing with Vertex Splitting is also NP-complete, resolving an open question by Abu-Khzam et al. [ISCO 2018]. We notice, however, that the proof of the critical-clique lemma is flawed and we give a counterexample. Our hardness result also holds under a version of the critical-clique lemma to which we currently do not have a counterexample. On the positive side, we show that Cluster Vertex Splitting admits a vertex-linear problem kernel with respect to the number of splits.Comment: 30 pages, 9 figure

The furan microsolvation blind challenge for quantum chemical methods: First steps

© 2018 Author(s). Herein we present the results of a blind challenge to quantum chemical methods in the calculation of dimerization preferences in the low temperature gas phase. The target of study was the first step of the microsolvation of furan, 2-methylfuran and 2,5-dimethylfuran with methanol. The dimers were investigated through IR spectroscopy of a supersonic jet expansion. From the measured bands, it was possible to identify a persistent hydrogen bonding OH-O motif in the predominant species. From the presence of another band, which can be attributed to an OH-π interaction, we were able to assert that the energy gap between the two types of dimers should be less than or close to 1 kJ/mol across the series. These values served as a first evaluation ruler for the 12 entries featured in the challenge. A tentative stricter evaluation of the challenge results is also carried out, combining theoretical and experimental results in order to define a smaller error bar. The process was carried out in a double-blind fashion, with both theory and experimental groups unaware of the results on the other side, with the exception of the 2,5-dimethylfuran system which was featured in an earlier publication

Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.Additional co-authors: Andreas J. Gruber, Franziska Hufsky, Henrike Indrischek, Sabina Kanton, Jörg Linde, Nelly Mostajo, Roman Ochsenreiter, Konstantin Riege, Lorena Rivarola-Duarte, Abdullah H. Sahyoun, Sita J. Saunders, Stefan E. Seemann, Andrea Tanzer, Bertram Vogel, Michael T. Wolfinger, Rolf Backofen, Jan Gorodkin, Ivo Grosse, Ivo Hofacker, Steve Hoffmann, Christoph Kaleta, Peter F. Stadler, Stephan Becker, and Manja Marz

Impact of newborn screening for SCID on the management of congenital athymia

BACKGROUND: Newborn screening (NBS) programmes for severe combined immunodeficiency (SCID) facilitate early SCID diagnosis and promote early treatment with haematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS due to severe T-cell lymphopaenia. With the expanding introduction of NBS programmes, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH), London, United Kingdom. OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared the age at referral and complications between athymic infants diagnosed after clinical presentation (N=25) and patients identified through NBS (N=19), referred for thymus transplantation at GOSH between 10/2019 and 02/2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: Infants referred after NBS identification were significantly younger and had less complications, in particular less infections. All deaths occurred in the non-NBS group, including six patients before and two after thymus transplantation because of pre-existing infections. In the absence of significant co-morbidities or diagnostic uncertainties, timely treatment was more frequently achieved after NBS. Treatment at <4 months of age was associated with higher thymic output at 6- and 12-months post-transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation prior to acquiring infections or other complications, and facilitating treatment at younger age, thus playing an important role in improving their outcomes

TURBOMOLE: Today and Tomorrow

TURBOMOLE is a highly optimized software suite for large-scale quantum-chemical and materials science simulations of molecules, clusters, extended systems, and periodic solids. TURBOMOLE uses Gaussian basis sets and has been designed with robust and fast quantum-chemical applications in mind, ranging from homogeneous and heterogeneous catalysis to inorganic and organic chemistry and various types of spectroscopy, light–matter interactions, and biochemistry. This Perspective briefly surveys TURBOMOLE’s functionality and highlights recent developments that have taken place between 2020 and 2023, comprising new electronic structure methods for molecules and solids, previously unavailable molecular properties, embedding, and molecular dynamics approaches. Select features under development are reviewed to illustrate the continuous growth of the program suite, including nuclear electronic orbital methods, Hartree–Fock-based adiabatic connection models, simplified time-dependent density functional theory, relativistic effects and magnetic properties, and multiscale modeling of optical properties

The first microsolvation step for furans : new experiments and benchmarking strategies

The site-specific first microsolvation step of furan and some of its derivatives with methanol is explored to benchmark the ability of quantum-chemical methods to describe the structure, energetics, and vibrational spectrum at low temperature. Infrared and microwave spectra in supersonic jet expansions are used to quantify the docking preference and some relevant quantum states of the model complexes. Microwave spectroscopy strictly rules out in-plane docking of methanol as opposed to the top coordination of the aromatic ring. Contrasting comparison strategies, which emphasize either the experimental or the theoretical input, are explored. Within the harmonic approximation, only a few composite computational approaches are able to achieve a satisfactory performance. Deuteration experiments suggest that the harmonic treatment itself is largely justified for the zero-point energy, likely and by design due to the systematic cancellation of important anharmonic contributions between the docking variants. Therefore, discrepancies between experiment and theory for the isomer abundance are tentatively assigned to electronic structure deficiencies, but uncertainties remain on the nuclear dynamics side. Attempts to include anharmonic contributions indicate that for systems of this size, a uniform treatment of anharmonicity with systematically improved performance is not yet in sight

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field