Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins

Using a high throughput screening methodology we surveyed a collection of largely uncharacterized validated or suspected kinase inhibitors for anti-human cytomegalovirus (HCMV) activity. From this screen we identified three structurally related 5-aminopyrazine compounds (XMD7-1, -2 and -27) that inhibited HCMV replication in virus yield reduction assays at low micromolar concentrations. Kinase selectivity assays indicated that each compound was a kinase inhibitor capable of inhibiting a range of cellular protein kinases. Western blotting and RNA sequencing demonstrated that treatment of infected cells with XMD7 compounds resulted in a defect in the production of the major HCMV transcriptional transactivator IE2 proteins (IE2-86, IE2-60 and IE2-40) and an overall reduction in transcription from the viral genome. However, production of certain viral proteins was not compromised by treatment with XMD7 compounds. Thus, these novel anti-HCMV compounds likely inhibited transcription from the viral genome and suppressed production of a subset of viral proteins by inhibiting IE2 protein production

Introducing a new measure of energy transition: Green quality of energy mix and its impact on CO2 emissions

YesThis paper introduces a novel measure of the energy transition, i.e., the green quality of energy mix (GREENQ) across the Organisation for Economic Co-operation and Development (OECD) countries. Then, the paper examines the impact of the GREENQ on CO2 emissions in the panel dataset of 36 OECD countries from 1970 to 2021. The explanatory variables include per capita income, institutional quality and technology. Long-run panel data estimations indicate that per capita income, institutional quality and technology increase CO2 emissions. The novel evidence is that the GREENQ is negatively related to the level of CO2 emissions. These findings are robust to employ different panel data estimation techniques. Potential policy implications are also discussed.The project was funded by the “Foreign Cultural and Educational Experts Project of the Ministry of Science and Technology of China” (Project Number: DL2022180001L)

Linker-Controlled Polymeric Photocatalyst for Highly Efficient Hydrogen Evolution from Water

Polymeric photocatalysts have been identified as promising materials for H2 production from water due to their comparative low cost and facile modification of the electronic structure. However, the majority only respond to a limited wavelength region (λ 420 nm), with an apparent quantum yield (AQY) of 10.3% at 420 nm and 2.1% at 500 nm, measured under ambient conditions, which is closer to the real environment (instead of vacuum conditions). The strategy used here thus paves a new avenue to dramatically tune both the light absorption and charge separation to increase the activity of polymeric photocatalysts

Large enhancement of deuteron polarization with frequency modulated microwaves

We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liters polarized target using the method of dynamic nuclear polarization. This target was used during a deep inelastic polarized muon-deuteron scattering experiment at CERN. Measurements of the electron paramagnetic resonance absorption spectra show that frequency modulation gives rise to additional microwave absorption in the spectral wings. Although these results are not understood theoretically, they may provide a useful testing ground for the deeper understanding of dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar files in poltar.uu, which also brings cernart.sty and crna12.sty files neede

Radio Science Investigation on a Mercury Orbiter Mission

We review the results from {\it Mariner 10} regarding Mercury's gravity field and the results from radar ranging regarding topography. We discuss the implications of improving these results, including a determination of the polar component, as well as the opportunity to perform relativistic gravity tests with a future {\it Mercury Orbiter}. With a spacecraft placed in orbit with periherm at 400 km altitude, apherm at 16,800 km, period 13.45 hr and latitude of periherm at +30 deg, one can expect a significant improvement in our knowledge of Mercury's gravity field and geophysical properties. The 2000 Plus mission that evolved during the European Space Agency (ESA) {\it Mercury Orbiter} assessment study can provide a global gravity field complete through the 25th degree and order in spherical harmonics. If after completion of the main mission, the periherm could be lowered to 200 km altitude, the gravity field could be extended to 50th degree and order. We discuss the possibility that a search for a Hermean ionosphere could be performed during the mission phases featuring Earth occultations. Because of its relatively large eccentricity and close proximity to the Sun, Mercury's orbital motion provides one of the best solar-system tests of general relativity. Consequently, we emphasize the number of feasible relativistic gravity tests that can be performed within the context of the parameterized post-Newtonian formalism - a useful framework for testing modern gravitational theories. We pointed out that current results on relativistic precession of Mercury's perihelion are uncertain by 0.5 %, and we discuss the expected improvement using {\it Mercury Orbiter}. We discuss the importance of {\it Mercury Orbiter} for setting limits on a possible time variation in theComment: 23 pages, LaTeX, no figure

A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer.

BACKGROUND: Molecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers. METHODS: We combined immunohistochemistry (IHC) with RNA sequencing and whole-genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+ T-cell infiltration of the TIME. Furthermore, we explored transcriptional features of immune archetypes and T-cell receptor sequencing diversity, assessed the relationship between CD8+ and CD4+ abundance by IHC and deconvolution predictions and assessed the common adult biomarkers such as neoantigen load and TMB. RESULTS: A novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells. CONCLUSIONS: Our data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in high-risk paediatric cancer will require individualised analysis of the TIME.Chelsea Mayoh, Andrew J. Gifford, Rachael Terry, Loretta M. S. Lau, Marie Wong, Padmashree Rao, Tyler Shai, Hee, Federica Saletta, Dong, Anh Khuong, Quang, Vicky Qin, Marion K. Mateos, Deborah Meyran, Katherine E. Miller, Aysen Yuksel, Emily V. A. Mould, Rachel Bowen, James, Dinisha Govender, Akanksha Senapati, Nataliya Zhukova, Natacha Omer, Hetal Dholaria, Frank Alvaro, Heather Tapp, Yonatan Diamond, Luciano Dalla Pozza, Andrew S. Moore, Wayne Nicholls, Nicholas G. Gottardo, Geoffrey McCowage, Jordan R. Hansford, Seong, Lin Khaw, Paul J. Wood, Daniel Catchpoole, Catherine E. Cottrell, Elaine R. Mardis, Glenn M. Marshall, Vanessa Tyrrell, Michelle Haber, David S. Ziegler, Orazio Vittorio, Joseph A. Trapani, Mark J. Cowley, Paul J. Neeson, and Paul G. Eker

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements