Oxidative Stress is a shared characteristic of ME/CFS and Long COVID.

More than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, and 15 LC, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, relative to healthy controls, especially in the memory subset. Using a combination of flow cytometry, bulk RNA-seq analysis, mass spectrometry, and systems chemistry analysis, we also observed aberrations in ROS clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase levels, and glutathione peroxidase 4 mediated lipid oxidative damage. Critically, these changes in redox pathways show striking sex-specific trends. While females diagnosed with ME/CFS exhibit higher total ROS and mitochondrial calcium levels, males with an ME/CFS diagnosis have normal ROS levels, but larger changes in lipid oxidative damage. Further analyses show that higher ROS levels correlates with hyperproliferation of T cells in females, consistent with the known role of elevated ROS levels in the initiation of proliferation. This hyperproliferation of T cells can be attenuated by metformin, suggesting this FDA-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Thus, we report that both ME/CFS and LC are mechanistically related and could be diagnosed with quantitative blood cell measurements. We also suggest that effective, patient tailored drugs might be discovered using standard lymphocyte stimulation assays.

Now Is the Time to Build a National Data Ecosystem for Materials Science and Chemistry Research Data.

Research organizations are critically in need of directed growth toward future interoperability and federation. The purpose of this Viewpoint is to alert the government, academia, professional societies, foundations, and industries of a further need for consideration of data in chemistry and materials as a long-term and sustained development in the US. This paper is a call for coordinated action from the government, academia, and industry to establish a national strategy and concomitant infrastructure focused on research data.

Physical bioenergetics: Energy fluxes, budgets, and constraints in cells.

Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge. Physical bioenergetics, which resides at the interface of nonequilibrium physics, energy metabolism, and cell biology, seeks to understand how much energy cells are using, how they partition this energy between different cellular processes, and the associated energetic constraints. Here we review recent advances and discuss open questions and challenges in physical bioenergetics.

Correction: Phase stability in nanoscale material systems: extension from bulk phase diagrams.

Correction for 'Phase stability in nanoscale material systems: extension from bulk phase diagrams' by Saurabh Bajaj et al., Nanoscale, 2015, 7, 9868-9877.

Phase stability in nanoscale material systems: extension from bulk phase diagrams.

Phase diagrams of multi-component systems are critical for the development and engineering of material alloys for all technological applications. At nano dimensions, surfaces (and interfaces) play a significant role in changing equilibrium thermodynamics and phase stability. In this work, it is shown that these surfaces at small dimensions affect the relative equilibrium thermodynamics of the different phases. The CALPHAD approach for material surfaces (also termed "nano-CALPHAD") is employed to investigate these changes in three binary systems by calculating their phase diagrams at nano dimensions and comparing them with their bulk counterparts. The surface energy contribution, which is the dominant factor in causing these changes, is evaluated using the spherical particle approximation. It is first validated with the Au-Si system for which experimental data on phase stability of spherical nano-sized particles is available, and then extended to calculate phase diagrams of similarly sized particles of Ge-Si and Al-Cu. Additionally, the surface energies of the associated compounds are calculated using DFT, and integrated into the thermodynamic model of the respective binary systems. In this work we found changes in miscibilities, reaction compositions of about 5 at%, and solubility temperatures ranging from 100-200 K for particles of sizes 5 nm, indicating the importance of phase equilibrium analysis at nano dimensions.

Extended temperature-accelerated dynamics: enabling long-time full-scale modeling of large rare-event systems.

A new method, the Extended Temperature-Accelerated Dynamics (XTAD), is introduced for modeling long-timescale evolution of large rare-event systems. The method is based on the Temperature-Accelerated Dynamics approach [M. Sørensen and A. Voter, J. Chem. Phys. 112, 9599 (2000)], but uses full-scale parallel molecular dynamics simulations to probe a potential energy surface of an entire system, combined with the adaptive on-the-fly system decomposition for analyzing the energetics of rare events. The method removes limitations on a feasible system size and enables to handle simultaneous diffusion events, including both large-scale concerted and local transitions. Due to the intrinsically parallel algorithm, XTAD not only allows studies of various diffusion mechanisms in solid state physics, but also opens the avenue for atomistic simulations of a range of technologically relevant processes in material science, such as thin film growth on nano- and microstructured surfaces.

Divacancies in carbon nanotubes and their influence on electron scattering.

First-principles calculations are applied to study the formation energies of various divacancy defects in armchair and zigzag carbon nanotubes of varying diameter, and the transport properties for the corresponding structures. Our explicit ab initio calculations confirm that the lateral 585 divacancy is the most stable defect in small diameter tubes, with the 555 777 divacancy becoming more stable in armchair tubes larger than (30, 30). Evaluating the electron transmission as a function of diameter and chirality for a range of defects, the strongest scattering is found for the 555 777 divacancy configuration, which is observable in electrical spectroscopy experiments. Finally, validation of an approximation relating contributions from independent scattering sites enables the study of the characteristic localization length in large diameter tubes. Despite the fixed number of channels, localization lengths increase with increasing diameter and can exceed 100 nm for typical defect densities.

Density functional theory and beyond-opportunities for quantum methods in materials modeling semiconductor technology.

In the semiconductor industry, the use of new materials has been increasing with the advent of nanotechnology. As critical dimensions decrease, and the number of materials increases, the interactions between heterogeneous materials themselves and processing increase in complexity. Traditionally, applications of ab initio techniques are confined to electronic structure and band gap calculations of bulk materials, which are then used in coarse-grained models such as mesoscopic and continuum models. Density functional theory is the most widely used ab initio technique that was successfully extended to several applications. This paper illustrates applications of density functional theory to semiconductor processes and proposes further opportunities for use of such techniques in process development.

Systemic Thrombolytic Therapy for Early Coronary stent Thrombosis: An Observational Study.

BACKGROUND: Early stent thrombosis following coronary angioplasty is associated with high mortality and morbidity. Different methods of treatment, including emergency coronary angioplasty, have been tried, but with variable results. This is a study of the results of systemic thrombolytic therapy in the treatment of early stent thrombosis. METHODS: Eight patients, who developed acute chest pain and ST-segment elevation within the first few days of coronary stenting, were administered 1.5 million units of streptokinase or urokinase and followed up for acute and long-term events. RESULTS: Seven patients responded well. The ST-segment resolution was excellent and the clinical outcome good. One patient who presented late after the onset of chest pain and received urokinase, expired. CONCLUSION: Systemic thrombolytic therapy seems to compare favorably with emergency coronary angioplasty in the treatment of early coronary stent thrombosis. Further experience is required to define its role better.