An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques

Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB₄), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr⁻/⁻ mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB₄ ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability

Supporting Clinical Decision-Making during the SARS-CoV-2 Pandemic through a Global Research Commitment: The TERAVOLT Experience.

To understand the real impact of COVID-19 on cancer patients, an entirely new data collection effort was initiated within the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT). TERAVOLT reported high mortality related to COVID-19 infection in thoracic cancer patients and identified several negative prognostic factors. In this commentary, we discuss the importance and limits of patient registries to support decision-making in thoracic cancer during the SARS-CoV-2 pandemic

Исследование кристаллизации NaCl из водного раствора, находящегося в магнитном поле

In the context of developing single-site stereoselective post-metallocene catalysts, the case for isospecific styrene polymerization catalysts based on methylaluminoxane-activated group 4 metal bis(phenolato) complexes is summarized. In the context of developing single-site stereoselective post-metallocene catalysts, the case for isospecific styrene polymerization catalysts based on methylaluminoxane-activated group 4 metal bis(phenolato) complexes is summarized. Ligands derived from the 1,4-dithiabutanediyl-linked bis(phenol)s have been found to induce stereochemical rigidity by the presence of the hemi-labile sulfide donor functions. Isospecific styrene polymerization was achieved using easily accessible catalyst precursors of the type [MX 2(OC6H2-tBu2-4,6) 2S(CH2)2S] (M = Ti, Zr, Hf; X = Cl, O iPr, CH2Ph). Activating the dibenzyl titanium complex [Ti(CH2Ph)2(OC6H2- tBu2-4,6)2S(CH2)2S] with B(C6F5)3 and AliBu3, controlled isotactic polymerization became possible at lower temperatures. A remarkable dependence of both the activity and stereoselectivity on the ligand substitution pattern was observed. Analogous precursors with the 1,5-dithiapentanediyl-linked bis(phenolato) ligand gave syndiotactic polystyrene with lower activity. © 2004 Elsevier B.V. All rights reserved

Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review

Background: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology. Materials and methods: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data. Results: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data. Conclusion: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice

Who Invited You? The Complex Story Of Aquatic Invasive Species

Invasive species represent a global threat to ecosystems, human health, and the economy. A basic knowledge of invasive species biology is crucial to understand current and future impacts and implications. The purpose of this book is to provide a broad background on invasive species, and also details on specific examples through case studies. The students in the course Aquatic Invasive Species (MAR 442) at the University of New England in Biddeford, Maine, have researched and reviewed scientific literature to educate readers about these issues. The class, comprised of fifteen junior and senior Marine Science, Marine Affairs, Animal Behavior, and Environmental Sciences students, selected the different topics, presented the material, wrote the chapters, and assembled the final versions into this book. This book cannot be all inclusive, but we think this book will provide an excellent broad overview of the most important aspects of Invasive Species Biology and might stimulate the reader to dive deeper into the material.https://dune.une.edu/marinesci_studproj/1003/thumbnail.jp

Physics potentials with the second Hyper-Kamiokande Detector in Korea

Hyper-Kamiokande consists of two identical water-Cherenkov detectors of total 520 kt, with the first one in Japan at 295 km from the J-PARC neutrino beam with 2.5 degrees off-axis angles (OAAs), and the second one possibly in Korea at a later stage. Having the second detector in Korea would benefit almost all areas of neutrino oscillation physics, mainly due to longer baselines. There are several candidate sites in Korea with baselines of 1000-1300 km and OAAs of 1 degrees-3 degrees. We conducted sensitivity studies on neutrino oscillation physics for a second detector, either in Japan (JD x 2) or Korea (JD + KD), and compared the results with a single detector in Japan. Leptonic charge-parity (CP) symmetry violation sensitivity is improved, especially when the CP is non-maximally violated. The larger matter effect at Korean candidate sites significantly enhances sensitivities to non-standard interactions of neutrinos and mass ordering determination. Current studies indicate the best sensitivity is obtained at Mt. Bisul (1088 km baseline, 1.3 degrees OAA). Thanks to a larger (1000 m) overburden than the first detector site, clear improvements to sensitivities for solar and supernova relic neutrino searches are expected

Imitation and intangibility: postmodern perspectives on restoration and authenticity at the Hill House Box, Scotland

Restoration is often problematised within built heritage practice as an inauthentic activity of imitation. This is symptomatic of a Western focus on physical heritage sites, which is underpinned by an amalgam of scientific materialism and visual aesthetics. Situated within a postmodern conceptualisation of heritage as increasingly dynamic, social and intangible, this study suggests the relationship between restoration and authenticity is increasingly out of step with contemporary perspectives and would benefit from a critical gaze. Drawing on Baudrillard’s theory of ‘hyperreality’, this study makes space for two key concepts within the built heritage paradigm: authenticity as emergent and fluid; and the legitimisation of imitation as a valid activity. Together, these are explored in relation to the restoration of the Hill House, Scotland, and its encapsulation within the ‘Hill House Box’. From a postmodern, Baudrillardian outlook, the site becomes a dynamic performance between the restored building (a tangible ‘simulation’ of an idealised essence) and the users of the Hill House Box (an intangible, ritualised experience). Consequently, this demonstrates how the amalgamation of imitation and intangibility can overcome binary views of original/copy; authentic/inauthentic, resulting in the creation of emergent authenticity and aura that the Box both creates and is engulfed within

Positional Income Concerns: Prevalence and Relationship with Personality and Economic Preferences

This paper presents detailed evidence about who compares to whom in terms of relative income. We rely on representative survey data on the importance of income comparisons vis-á-vis seven reference groups, allowing us to exploit within-subject heterogeneity. We explore the prevalence and determinants of positional income concerns, investigating the role of personality and economic preferences. Our results establish robust relationships between positional income concerns and the personality traits agreeableness, conscientiousness, and neuroticism, some of which depend on the reference group. Furthermore, risk and fairness preferences are significantly correlated with positional income concerns

Protection of Hepatocytes from Cytotoxic T Cell Mediated Killing by Interferon-Alpha

<p>Background: Cellular immunity plays a key role in determining the outcome of hepatitis C virus (HCV) infection, although the majority of infections become persistent. The mechanisms behind persistence are still not clear; however, the primary site of infection, the liver, may be critical. We investigated the ability of CD8+ T-cells (CTL) to recognise and kill hepatocytes under cytokine stimulation.</p> <p>Methods/Principle Findings: Resting hepatocytes cell lines expressed low levels of MHC Class I, but remained susceptible to CTL cytotoxicity. IFN-α treatment, in vitro, markedly increased hepatocyte MHC Class I expression, however, reduced sensitivity to CTL cytotoxicity. IFN-α stimulated hepatocyte lines were still able to present antigen and induce IFN-γ expression in interacting CTL. Resistance to killing was not due to the inhibition of the FASL/FAS- pathway, as stimulated hepatocytes were still susceptible to FAS-mediated apoptosis. In vitro stimulation with IFN-α, or the introduction of a subgenomic HCV replicon into the HepG2 line, upregulated the expression of the granzyme-B inhibitor–proteinase inhibitor 9 (PI-9). PI-9 expression was also observed in liver tissue biopsies from patients with chronic HCV infection.</p> <p>Conclusion/Significance: IFN-α induces resistance in hepatocytes to perforin/granzyme mediate CTL killing pathways. One possible mechanism could be through the expression of the PI-9. Hindrance of CTL cytotoxicity could contribute to the chronicity of hepatic viral infections.</p&gt

Proposed antimatter gravity measurement with an antihydrogen beam

The principle of the equivalence of gravitational and inertial mass is one of the cornerstones of general relativity. Considerable efforts have been made and are still being made to verify its validity. A quantum-mechanical formulation of gravity allows for non-Newtonian contributions to the force which might lead to a difference in the gravitational force on matter and antimatter. While it is widely expected that the gravitational interaction of matter and of antimatter should be identical, this assertion has never been tested experimentally. With the production of large amounts of cold antihydrogen at the CERN Antiproton Decelerator, such a test with neutral antimatter atoms has now become feasible. For this purpose, we have proposed to set up the AEGIS experiment at CERN/AD, whose primary goal will be the direct measurement of the Earth's gravitational acceleration on antihydrogen with a classical Moiré deflectometer. © 2007 Elsevier B.V. All rights reserved