17 research outputs found
Aging- and obesity-associated metabolic reprogramming suppresses CD8+ T cell responses
No full textAging and obesity are growing global health issues and are associated with increased susceptibility towards infectious diseases, increased cancer risk and decreased vaccination efficacy. CD8+ T cells are the main effectors of cell-mediated adaptive immunity and form antigen-specific memory after pathogen clearance. However, upon antigen persistence during cancer or chronic infections, T cells become dysfunctional, a state termed T cell exhaustion. In CD8+ T cells, the transcription factor T cell factor 1 (TCF1, encoded by Tcf7) is a stemness marker and high expression is associated with CD8+ T cell longevity and superior functionality. The aim of this study was to identify synergistic effects of aging and obesity on the CD8+ T cell phenotype and function as well as on the plasma metabolite profile to ultimately find a causal relation.
A diet-induced obesity mouse model of young and aged mice was used to study the effect of aging and obesity on the CD8+ T cell phenotype as well as on the plasma metabolite profile. Flow cytometric analysis of naïve CD8+ T cells revealed a terminally differentiated, exhausted CD8+ T cell phenotype with reduced TCF1 expression in aged obese compared to young lean mice. Mass spectrometric analysis of plasma samples identified the tryptophan metabolite 3-Indolepropionic acid (3-IPA) to be synergistically decreased by aging and obesity. Treatment of primary murine and human CD8+ T cells with 3-IPA in therapeutic concentrations, increased TCF1 expression as well as other stemness markers and reversed T cell exhaustion in vitro. Using the lymphocytic choriomeningitis virus (LCMV) infection model, 3-IPA pre-treatment of antigen-specific CD8+ T cells rescued aging- and obesity-impaired anti-viral CD8+ T cell effector and memory functions.
To elucidate the molecular mechanism how 3-IPA increases CD8+ T cell stemness, a pull-down experiment was performed and γ-catenin was identified as a 3-IPA-binding protein. Further investigations revealed decelerated degradation of γ-catenin and its close homologue β-catenin upon 3-IPA treatment in activated CD8+ T cells. Moreover, 3-IPA treatment increased Tcf7 promoter activity in a luciferase assay, while the role of β- and γ-catenin in this context remains elusive.
In summary, aging and obesity synergistically decreased stemness, recall capacity and anti-viral effector functions of CD8+ T cells, thus making them a detrimental combination. Treatment of CD8+ T cells with 3-IPA restored those defects, suggesting a therapeutic potential of 3-IPA to overcome aging- and obesity-mediated CD8+ T cell dysfunctionality
Quantum Computing Impact Now and the Future
No full textAbstract: The potential for quantum computing to disrupt a variety of industries by solving challenging computational problems more effectively than traditional computers has recently come to light. Quantum computers use qubits rather than conventional bits, utilizing the laws of quantum mechanics to enable exponential parallelism and the processing of massive amounts of data at once. This paper addresses the prospective applications of quantum computing and the potential effects it may have on many sectors, such as the Chemical, Aerospace And Defense, Life Sciences, Financial, Natural Gas, Cybersecurity, and Logistics Industries.
Keywords: quantum computing, potentials, industries, chemicals, aerospace and defense, life sciences, finance, natural gas, cybersecurity, and logistics.
Title: Quantum Computing Impact Now and the Future
Author: Abdullah Saad Alessa
International Journal of Computer Science and Information Technology Research
ISSN 2348-1196 (print), ISSN 2348-120X (online)
Vol. 11, Issue 3, July 2023 - September 2023
Page No: 125-127
Research Publish Journals
Website: www.researchpublish.com
Published Date: 26-August-2023
DOI: https://doi.org/10.5281/zenodo.8285375
Paper Download Link (Source)
https://www.researchpublish.com/papers/quantum-computing-impact-now-and-the-futureInternational Journal of Computer Science and Information Technology Research, ISSN 2348-1196 (print), ISSN 2348-120X (online), Research Publish Journals, Website: www.researchpublish.co
Investigation of Chrysene heterodimers complexes potential energy surface using ab initio computational methods
No full textNumerous chemical and biological entities are greatly impacted by non-covalent interactions in terms of their stability and structure. One such example is the interaction of aromatic rings. These interactions are highly valued in the domains of astrochemistry, biology, chemistry, biochemistry, and material science. The main goals of this study are to explore the Potential Energy Surface (PES) of Chrysene (Chy) heterodimers, identify the most stable configurations among the Chy-Bz, Chy-Np, and Chy-Anth heterodimer complexes, and analyze the inter-molecular interactions between these molecules. This analysis was conducted utilizing ab initio computational techniques. On their PES, the Chy-Np heterodimer exhibited four minima, while the Chy-Bz and Chy-Anth heterodimer complexes showed three. Compared to conformers oriented perpendicularly, co-facial arrangement conformers in Chy heterodimer complexes have stable structures. The global minimum structure of Chy-Bz has been determined to be the face isomer, while Chy-Np and Chy-Anth have global minimum structures of the cross isomer. The binding energies of the structures generated by MP2 are higher than those of DFT-D3, DFT-D4, and SCS-MP2. Optimized geometries and binding energies of larger hydrocarbon aromatic systems are explained in detail by B3LYP-D3 and the recently created B3LYP-D4.The author thanks King Abdullah University of Science and Technology KAUST for providing the Shaheen Supercomputer to be able to contribute the calculations
Analyzing the Energetics of the Four Aromatic Ring Interactions: Theoretical Study.
No full textDespite the growing significance of noncovalent interactions in modern chemical studies, a comprehensive conception of fundamental noncovalent interactions remains elusive. The field still lacks a thorough understanding of these prototype interactions. Specifically, the nature of π-π and C-H···π interactions is not fully understood. These interactions are prevalent in biological systems, supramolecular chemistry, physics, and material science. Many aspects remain unclear, including their intensity, geometric dependencies, energetics, interactions, effects of substituents, and underlying physical principles. The dimers of four Fused Aromatic Rings (4FARs), Benz[a]anthracene (BA), Chrysene (Chy), Tetracene (Tet), and Triphenylene (Tri), have been investigated using Interaction Energy (IE), Stabilization Energy (ESAPT), frontier orbital gaps, and aromaticity indices (FLU, PDI, HOMA, and PLR). Additionally, real-space analyses (QTAIM and NCI) and crystal-topology descriptors (Hirshfeld surfaces and 2D fingerprints) are employed. These methods facilitate the study of stability, energy, and strength of noncovalent interactions as well as the preferred structure of dimer arrangements. Theoretical computations of these homodimer complexes indicate a weak correlation between the interaction and stabilization energies, as well as results from the HOMO-LUMO energy gap and Clar π sextet rule. However, aromaticity, QTAIM, NCI, and Hirshfeld analyses were employed to investigate intermolecular interactions, yielding an agreement with the interaction and stabilization energies. These theoretical methods agree on conformers; therefore, cross-conformers are more stable than face conformers. In terms of 4FAR homodimer configurations, the Tet conformer with a linear geometry is the most stable. However, the Tri conformer with a compact geometry is the lowest stable. The 4FAR homodimer complexes are stabilized by the dominant π-π stacking, which is the critical point.The author thanks King Abdullah University of Science and Technology KAUST for providing the Shaheen Supercomputer to be able to contribute the calculations
The influence of human resource practices on employees’ responses towards organizational change in the automotive industry: transformational leadership as a mediator
No full textOrganizational change, specifically the human dimension of change, is central to the corporate strategy of manufacturers and suppliers in the automotive industry in the 21st century. However, little research was conducted on the relation between commitment-based human resource practices and employees’ responses towards organizational change and future organizational change so far. The present study investigated the effects of commitment-based human resource (HR) practices, transformational leadership, and psychological safety on employees’ responses to organizational change and to future organizational change in the automotive industry. The author hypothesized that commitment-based HR practices are linked to favorable employee responses towards organizational change (1a) and future organizational change (1b); transformational leadership mediates the positive effect of commitment-based HR practices on employees’ change responses (2a) and employees’ responses to future change (2b); psychological safety mediates the positive effect of commitment-based HR practices on employees’ change responses (3a) and employees’ responses to future change (3b); and the positive relation between commitment-based HR practices and employees’ change responses (4a) and employees’ responses to future change (4b) is mediated by both high transformational leadership and high psychological safety (double mediation). 117 participants from different automobile manufacturers in Germany completed a cross-sectional survey. The results revealed a main effect of commitment-based HR practices on employees’ change responses, confirming the hypotheses 1a and 1b. Process analyses showed a full mediation effect of transformational leadership in the relation of commitment-based HR practices and employees’ change responses, confirming hypotheses 2a and 2b. The third hypothesis was not supported, since no full indirect effect of psychological safety in the relation of commitment-based HR practices and employees’ change responses was found. Finally, no serial double mediation effect of transformational leadership and psychological safety in the association of commitment-based HR practices and employees’ change responses was found, disconfirming hypotheses 4a and 4b. Based both on the theories of social exchanges and uncertainty reduction, the findings highlight how commitment-based HR practices contribute to lower change resistance and change disengagement and to higher change acceptance and change proactivity among employees at German automobile manufacturers.
Keywords: responses to organizational change, commitment-based HR practices, transformational leadership, psychological safety, automotive industr
Efficiency and contribution of strategies for finding randomized controlled trials: a case study from a systematic review on therapeutic interventions of chronic depression
No full textBackground. Identifying all existing evidence is a crucial aspect in conducting systematic reviews. Since the retrieval of electronic database searches alone is limited, guidelines recommend the use of addi- tional search strategies. The aim of this investigation was to assess the efficiency and contribution of additional search strategies for identifying randomized controlled trials in conducting a systematic review on interventions after performing a sensitive electronic database search. Design and Methods. Seven electronic databases, 3 journals and 11 systematic reviews were searched. All first authors of the included studies were contacted; citation tracking and a search in clinical trial registers were performed. A priori defined evaluation criteria were calculated for each search strategy. Results. A total of 358 full-text articles were identified; 50 studies were included in the systematic review, wherefrom 84.0% (42) were acquired by the sensitive electronic database search and 16.0% (8) through additional search strategies. Screening reference lists of related systematic reviews was the most beneficial additional search strategy, with an efficiency of 31.3% (5) and a contribution of 10.0% (5/50), whereas hand-searching and author contacts contributed two and one additional studies, respectively. Citation tracking and searching clinical trial registers did not lead to any further inclusion of primary studies. Conclusions. Based on our findings, hand-searching contents of relevant journals and screening reference lists of related systematic reviews may be helpful additional strategies to identify an extensive body of evidence. In case of limited resources, a sensitive electronic database search may constitute an appropriate alternative for identifying relevant trials
Assessing Innovations in High-Speed Rail Infrastructure
No full textInnovations in high-speed rail (HSR) have had substantial effects on different stakeholders within and outside the railway system. As part of the European Shift2Rail research programme, several innovative solutions are developed for, among others, improving the HSR infrastructure. The Joint Undertaking behind this research program has set objectives for these innovations in terms of punctuality, capacity, and life cycle costs. With a focus on infrastructure-related innovations for HSR, this paper aims at assessing their impacts in relation to these targets. We review the relevant research literature about the effects of HSR innovations and their assessment. The paper presents a hybrid assessment methodology combing different approaches to assess capacity, punctuality, and cost effects. This contributes to reducing the existing gap that is found in the research literature. Based on a reference scenario for HSR line and collected data from different stakeholders, the results indicate that infrastructure innovations in HSR, being developed within the European Shift2Rail research programme, can contribute to reaching the target set for punctuality. Further innovations in HSR infrastructure and/or other railway assets may be needed to reach additional targets and for more accurate improvement values giving more insights into their impacts. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.</p
Out of the blue: Vermeer’s use of ultramarine in Girl with a Pearl Earring
No full textJohannes Vermeer (1632–1675) is known for his brilliant blue colours, and his frequent use of the costly natural ultramarine. This paper reveals new findings about ultramarine in the headscarf of Girl with a Pearl Earring (c. 1665, Mauritshuis). The painting was examined using a range of micro- and macroscale techniques as part of the Girl in the Spotlight research project (2018). Analysis of micro-samples mounted as cross-sections using SEM–EDX and FTIR-ATR showed that Vermeer used high-quality ultramarine in the blue headscarf, based on the relative abundance of bright blue particles of lazurite. Analysis with synchrotron sulphur K-edge XANES suggested that the ultramarine pigment was prepared—at least in part—from a heat-treated lapis lazuli rock. The entire painting was imaged using MS-IRR, MA-XRF, RIS, and digital microscopy to reveal the distribution of materials of the headscarf, and to give more insight into Vermeer’s painting process. The shadow part of the headscarf has a remarkably patchy appearance, due to paint degradation that is probably related to the large amounts of chalk Vermeer mixed in the ultramarine paint in this area. The question was raised as to whether extra chalk was added deliberately to the paint to adjust the handling properties or opacity, or whether the chalk was the substrate of a—now faded—yellow lake. Schematic paint reconstructions were made to investigate the effect of the addition of chalk or yellow lake on the paint properties. The analyses and reconstructions led to the hypothesis that the blue headscarf originally contained a wider range of different blue colour shades: an opaque light blue for the left (lit) zone, a slightly brighter opaque blue for the middle zone, and a deep dark blue-green glaze with alternating blue-green glazing brushstrokes for the shadow zone—now largely compromised by paint degradation.(OLD) MSE-
Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma
No full textAbstract After recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation. Whether this recruitment of adaptor proteins is dependent solely on protein-protein interactions is unknown. Here, we report that the sphingolipid sphinganine physically interacts with the adaptor proteins MyD88 and TIRAP and promotes MyD88 recruitment in macrophages. Myeloid cell-specific deficiency in serine palmitoyltransferase long chain base subunit 2, which encodes the key enzyme catalyzing sphingolipid biosynthesis, decreases the membrane recruitment of MyD88 and inhibits inflammatory responses in in vitro bone marrow-derived macrophage and in vivo sepsis models. In a melanoma mouse model, serine palmitoyltransferase long chain base subunit 2 deficiency decreases anti-tumor myeloid cell responses and increases tumor growth. Therefore, sphinganine biosynthesis is required for the initiation of TLR4 signal transduction and serves as a checkpoint for macrophage pattern recognition in sepsis and melanoma mouse models
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Efficacy of clotrimazole for the management of oral candidiasis: A meta-analysis of randomized clinical trials
No full textPurpose: To assess the efficacy and safety of topical application of clotrimazole versus others in the treatment of oropharyngeal candidiasis (OPC). Method: Four electronic databases, registries of ongoing trials, and manual search were used to identify randomized controlled trials (RCTs) that compared the efficacy of clotrimazole to other antifungal agents in patients who were clinically diagnosed with oral candidiasis up to November 1st, 2019. Primary outcomes were clinical response and mycological cure rates. Secondary outcomes include relapse rate, incidence of systemic infections, and compliance. Adverse effects were also evaluated. Results: Sixteen RCTs with a total of 1685 patients were included. Half of the eligible studies were considered at high risk of performance bias and more than a third, at high risk of reporting bias. Our analysis showed no significant difference in clinical response between clotrimazole and all other antifungal agents. However, clotrimazole was less effective in terms of mycologic cure and relapse rate. Sensitivity analysis comparing clotrimazole to other topical antifungal agents only showed no differences in clinical response, microbiologic cure or relapse. Further sensitivity analysis showed significant efficacy of fluconazole over clotrimazole. Conclusion: This meta-analysis indicated that clotrimazole is less effective than fluconazole but as effective as other topical therapies in treating OPC. Well-designed high-quality RCT is needed to validate these findings. © 2021 The Author(s)Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
