Multiple-scattering effects on incoherent neutron scattering in glasses and viscous liquids

Incoherent neutron scattering experiments are simulated for simple dynamic models: a glass (with a smooth distribution of harmonic vibrations) and a viscous liquid (described by schematic mode-coupling equations). In most situations multiple scattering has little influence upon spectral distributions, but it completely distorts the wavenumber-dependent amplitudes. This explains an anomaly observed in recent experiments

Engineering of Pyroelectric Crystals Decoupled from Piezoelectricity as Illustrated by Doped α-Glycine

Design of pyroelectric crystals decoupled from piezoelectricity is not only a topic of scientific curiosity but also demonstrates effects in principle that have the potential to be technologically advantageous. Here we report a new method for the design of such materials. Thus, the co-doping of centrosymmetric crystals with tailor-made guest molecules, as illustrated by the doping of α-glycine with different amino acids (Threonine, Alanine and Serine). The polarization of those crystals displays two distinct contributions, one arising from the difference in dipole moments between guest and host and the other from the displacement of host molecules from their symmetry-related positions. These contributions exhibit different temperature dependences and response to mechanical deformation. Thus, providing a proof of concept for the ability to design pyroelectric materials with reduced piezoelectric coefficient (d22) to a minimal value, below the resolution limit of the method (<0.005 pm/V). © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.CICECO-Aveiro Institute of MaterialsIsraeli Ministry of Science with the Russian Foundation for Basic ResearchFundação para a Ciência e a Tecnologia, FCTRussian Foundation for Basic Research, РФФИ, (19‐52‐06004 MHTИ_a, 3‐16492)Israel Science Foundation, ISF, (1898/22)Ministerstwo Edukacji i Nauki, MNiSW, (N 075‐15‐2021‐677, UIDB/50011/2020, UIDP/50011/2020)Ural Federal University, UrFUMinistry of Science and Higher Education of the Russian Federation, (FEUZ-2020-0054)Funding text 1: This work was supported by the collaborative program of the Israeli Ministry of Science with the Russian Foundation for Basic Research (RFBR), grant #3‐16492. Russian partners thank RFBR for the financial support within the project #19‐52‐06004 MHTИ_a. The equipment of the Ural Center for Shared Use “Modern nanotechnology” Ural Federal University (Reg. N 2968) was used with the financial support of the Ministry of Science and Higher Education of the RF (Project N 075‐15‐2021‐677). This work was developed within the scope of project CICECO‐Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020) financed by national funds through the FCT—Foundation for Science and Technology (Portugal). IL thank the Israel Science Foundation for the financial support (#1898/22). The research made possible due to historic generosity of the Harold Perlman Family. VS is grateful for financial support of the Ministry of Science Higher Education of the Russian Federation (state task FEUZ‐2020‐0054). o oFunding text 2: This work was supported by the collaborative program of the Israeli Ministry of Science with the Russian Foundation for Basic Research (RFBR), grant #3-16492. Russian partners thank RFBR for the financial support within the project #19-52-06004 MHTИ_a. The equipment of the Ural Center for Shared Use “Modern nanotechnology” Ural Federal University (Reg. No 2968) was used with the financial support of the Ministry of Science and Higher Education of the RF (Project No 075-15-2021-677). This work was developed within the scope of project CICECO-Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020) financed by national funds through the FCT—Foundation for Science and Technology (Portugal). IL thank the Israel Science Foundation for the financial support (#1898/22). The research made possible due to historic generosity of the Harold Perlman Family. VS is grateful for financial support of the Ministry of Science Higher Education of the Russian Federation (state task FEUZ-2020-0054)

Dissolving the Dichotomies Between Online and Campus-Based Teaching: a Collective Response to The Manifesto for Teaching Online (Bayne et al. 2020)

This article is a collective response to the 2020 iteration of The Manifesto for Teaching Online. Originally published in 2011 as 20 simple but provocative statements, the aim was, and continues to be, to critically challenge the normalization of education as techno-corporate enterprise and the failure to properly account for digital methods in teaching in Higher Education. The 2020 Manifesto continues in the same critically provocative fashion, and, as the response collected here demonstrates, its publication could not be timelier. Though the Manifesto was written before the Covid-19 pandemic, many of the responses gathered here inevitably reflect on the experiences of moving to digital, distant, online teaching under unprecedented conditions. As these contributions reveal, the challenges were many and varied, ranging from the positive, breakthrough opportunities that digital learning offered to many students, including the disabled, to the problematic, such as poor digital networks and access, and simple digital poverty. Regardless of the nature of each response, taken together, what they show is that The Manifesto for Teaching Online offers welcome insights into and practical advice on how to teach online, and creatively confront the supremacy of face-to-face teaching

Vancomycin exposure and acute kidney injury outcome: A Snapshot From the CAMERA2 Study

Among patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia from a prospective randomized clinical trial, acute kidney injury (AKI) rates increased with increasing vancomycin exposure, even within the therapeutic range. AKI was independently more common for the (flu)cloxacillin group. Day 2 vancomycin AUC ≥470 mg·h/L was significantly associated with AKI, independent of (flu)cloxacillin receipt

Exploiting genomics for antimicrobial resistance surveillance at One Health interfaces.

The intersection of human, animal, and ecosystem health at One Health interfaces is recognised as being of key importance in the evolution and spread of antimicrobial resistance (AMR) and represents an important, and yet rarely realised opportunity to undertake vital AMR surveillance. A working group of international experts in pathogen genomics, AMR, and One Health convened to take part in a workshop series and online consultation focused on the opportunities and challenges facing genomic AMR surveillance in a range of settings. Here we outline the working group's discussion of the potential utility, advantages of, and barriers to, the implementation of genomic AMR surveillance at One Health interfaces and propose a series of recommendations for addressing these challenges. Embedding AMR surveillance at One Health interfaces will require the development of clear beneficial use cases, especially in low-income and middle-income countries. Evidence of directionality, risks to human and animal health, and potential trade implications were also identified by the working group as key issues. Addressing these challenges will be vital to enable genomic surveillance technology to reach its full potential for assessing the risk of transmission of AMR between the environment, animals, and humans at One Health interfaces.

The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

Background: The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. Methods: To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. Results: No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93–1.10, Ptrend=0.77; MDM2: HR=0.96, 95%CI: 0.84–1.09, Ptrend=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87–1.12, Ptrend=0.83; MDM2: HR=0.98, 95%CI: 0.80–1.21, Ptrend=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. Conclusion: There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers. O M Sinilnikova1,2, A C Antoniou3, J Simard4, S Healey5, M Léoné1, D Sinnett6,7, A B Spurdle5, J Beesley5, X Chen5, kConFab8, M H Greene9, J T Loud9, F Lejbkowicz10, G Rennert10, S Dishon10, I L Andrulis11,12, OCGN11, S M Domchek13, K L Nathanson13, S Manoukian14, P Radice15,16, I Konstantopoulou17, I Blanco18, A L Laborde19, M Durán20, A Osorio21, J Benitez21, U Hamann22, F B L Hogervorst23, T A M van Os24, H J P Gille25, HEBON23, S Peock3, M Cook3, C Luccarini26, D G Evans27, F Lalloo27, R Eeles28, G Pichert29, R Davidson30, T Cole31, J Cook32, J Paterson33, C Brewer34, EMBRACE3, D J Hughes35, I Coupier36,37, S Giraud1, F Coulet38, C Colas38, F Soubrier38, E Rouleau39, I Bièche39, R Lidereau39, L Demange40, C Nogues40, H T Lynch41, GEMO1,2,42, R K Schmutzler43, B Versmold43, C Engel44, A Meindl45, N Arnold46, C Sutter47, H Deissler48, D Schaefer49, U G Froster50, GC-HBOC43,44,45,46,47,48,49,50, K Aittomäki51, H Nevanlinna52, L McGuffog3, D F Easton3, G Chenevix-Trench5 and D Stoppa-Lyonnet42 on behalf of the Consortium of Investigators of Modifiers of BRCA1/

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Interaction of mammalian cells with polymorphonuclear leukocytes: Relative sensitivity to monolayer disruption and killing

Monolayers of murine fibrosarcoma cells that had been treated either with histone-opsonized streptococci, histone-opsonized Candida globerata , or lipoteichoic acid-anti-lipoteichoic acid complexes underwent disruption when incubated with human polymorphonuclear leukocytes (PMNs). Although the architecture of the monolayers was destroyed, the target cells were not killed. The destruction of the monolayers was totally inhibited by proteinase inhibitors, suggesting that the detachment of the cells from the monolayers and aggregation in suspension were induced by proteinases released from the activated PMNs. Monolayers of normal endothelial cells and fibroblasts were much more resistant to the monolayer-disrupting effects of the PMNs than were the fibrosarcoma cells. Although the fibrosarcoma cells were resistant to killing by PMNs, killing was promoted by the addition of sodium azide (a catalase inhibitor). This suggests that the failure of the PMNs to kill the target cells was due to catalase inhibition of the hydrogen peroxide produced by the activated PMNs. Target cell killing that occurred in the presence of sodium azide was reduced by the addition of a “cocktail” containing methionine, histidine, and deferoxamine mesylate, suggesting that hydroxyl radicals but not myeloperoxidase-catalayzed products were responsible for cell killing. The relative ease with which the murine fibrosarcoma cells can be released from their substratum by the action of PMNs, coupled with their insensitivity to PMN-mediated killing, may explain why the presence of large numbers of PMNs at the site of tumors produced in experimental animals by the fibrosarcoma cells is associated with an unfavorable outcome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44503/1/10753_2004_Article_BF00916759.pd