The Road Towards the ILC: Higgs, Top/QCD, Loops

The International Linear e+e- Collider (ILC) could go into operation in the second half of the upcoming decade. Experimental analyses and theory calculations for the physics at the ILC are currently performed. We review recent progress, as presented at the LCWS06 in Bangalore, India, in the fields of Higgs boson physics and top/QCD. Also the area of loop calculations, necessary to achieve the required theory precision, is included.Comment: 7 pages, 1 figure. Plenary talk given at the LCWS06 March 2006, Bangalore, India. Top part slightly enlarged, references adde

MICROMEGAS chambers for hadronic calorimetry at a future linear collider

Prototypes of MICROMEGAS chambers, using bulk technology and analog readout, with 1x1cm2 readout segmentation have been built and tested. Measurements in Ar/iC4H10 (95/5) and Ar/CO2 (80/20) are reported. The dependency of the prototypes gas gain versus pressure, gas temperature and amplification gap thickness variations has been measured with an 55Fe source and a method for temperature and pressure correction of data is presented. A stack of four chambers has been tested in 200GeV/c and 7GeV/c muon and pion beams respectively. Measurements of response uniformity, detection efficiency and hit multiplicity are reported. A bulk MICROMEGAS prototype with embedded digital readout electronics has been assembled and tested. The chamber layout and first results are presented

R^2 Dark Matter

There is a non-trivial four-derivative extension of the gravitational spectrum that is free of ghosts and phenomenologically viable. It is the so called $R^2$-gravity since it is defined by the only addition of a term proportional to the square of the scalar curvature. Just the presence of this term does not improve the ultraviolet behaviour of Einstein gravity but introduces one additional scalar degree of freedom that can account for the dark matter of our Universe.Comment: 6 pages, 1 figure, to appear in the Proceedings of the sixth International Workshop on the Dark Side of the Universe (DSU2010) Leon, Guanajuato, Mexico 1-6 June 201

Dark Matter and Higgs Sector

The inert doublet model is an extension of the Standard Model of Elementary Particles that is defined by the only addition of a second Higgs doublet without couplings to quarks or leptons. This minimal framework has been studied for many reasons. In particular, it has been suggested that the new degrees of freedom contained in this doublet can account for the Dark Matter of the Universe.Comment: 6 pages, 3 figures,To appear in the Proceedings of the sixth International Workshop on the Dark Side of the Universe (DSU2010) Leon, Guanajuato, Mexico 1-6 June 201

Dark matter searches at LHC

Besides Standard Model measurements and other Beyond Standard Model studies, the ATLAS and CMS experiments at the LHC will search for Supersymmetry, one of the most attractive explanation for dark matter. The SUSY discovery potential with early data is presented here together with some first results obtained with 2010 collision data at 7 TeV. Emphasis is placed on measurements and parameter determination that can be performed to disentangle the possible SUSY models and SUSY look-alike and the interpretation of a possible positive supersymmetric signal as an explanation of dark matter.Comment: 15 pages, 14 figures, Invited plenary talk given at DISCRETE 2010: Symposium On Prospects In The Physics Of Discrete Symmetries, 6-11 Dec 2010, Rome, Ital

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. © 2013 Dias et al

The International Linear Collider: Report to Snow mass 2021

DESY-22-045,IFT–UAM/CSIC–22-028, KEKPreprint2021-61,PNNL-SA-160884, SLAC-PUB-17662.ILC International Development Team and ILC community: et al.The International Linear Collider (ILC) is on the table now as a new global energy-frontier accelerator laboratory taking data in the 2030s. The ILC addresses key questions for our current understanding of particle physics. It is based on a proven accelerator technology. Its experiments will challenge the Standard Model of particle physics and will provide a new window to look beyond it. This document brings the story of the ILC up to date, emphasizing its strong physics motivation, its readiness for construction, and the opportunity it presents to the US and the global particle physics community.The work of the DESY group is supported by the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy, EXC 2121 \Quantum Universe", grant 390833306. The work of IFIC is supported by Projects No. PGC2018-094856-B-100 (MCIN/AEI), PROMETEO-2018/060 and CIDEGENT/2020/21 (Generalitat Valenciana) and iLINK Grant No. LINKB20065 (CSIC). The work of the KEK group is supported in part by JSPS KAKENHI Grant Numbers 16H02173 and 21H01077. The work of the SLAC group is supported by the US Department of Energy, contract DE{AC02{76SF00515. The work of James Brau is supported by the US Department of Energy grant DE-SC0017996. The work of Francesco Giovanni Celiberto is supported by the INFN/NINPHA project. The work of Sven Heinemeyer is supported in part by the grant PID2019-110058GB-C21 funded by MCIN/AEI/10.13039/501100011033 and by "ERDF A way of making Europe", and in part by the grant CEX2020-001007-S funded by MCIN/AEI/10.13039/501100011033. The work of Sunghoon Jung is supported by the National Research Foundation of Korea under grant NRF-2017R1D1A1B03030820. The work of Zhen Liu is supported in part by the U.S. Department of Energy (DOE) under grant No. DE-SC0022345. The work of Nathaniel Craig is supported in part by the U.S. Department of Energy under the grant DE-SC0011702. The work of Alessandro Papa is supported by the INFN/QFTCOLLIDERS project.The work of Junping Tian is supported in part by the Japan Society for the Promotion of Science under the Grant-in-Aid for Science Research 15H02083. The work of Graham Wilson is supported by the US National Science Foundation under award NSF 2013007.N

Bisindolylmaleimide IX: a Novel Anti-SARS-CoV2 Agent Targeting Viral Main Protease 3CLpro Demonstrated by Virtual Screening Pipeline and In-Vitro Validation Assays

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = 5903). The screening was performed against viral targets using three sequential docking modes (i.e., HTVS, SP, and XP). Virtual screening identified ∼290 potential inhibitors based on the criteria of energy, docking parameters, ligand, and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. The top lead from each target pool was further subjected to molecular dynamics simulation using the Desmond module. The resulting top eight hits were tested for their SARS-CoV-2 anti-viral activity in-vitro. Among these, a known inhibitor of protein kinase C isoforms, Bisindolylmaleimide IX (BIM IX), was found to be a potent inhibitor of SARS-CoV-2. Further, target validation through enzymatic assays confirmed 3CLpro to be the target. This is the first study that has showcased BIM IX as a COVID-19 inhibitor thereby validating our pipeline

Going Solo: findings from a survey of women ageing without a partner and who do not have children

Greater longevity in the UK population has led to the increasing diversity of women experiencing ageing in a multitude of ways. Internationally gender inequalities within ageing are still relatively invisible within both government policy and everyday life for particular groups of women. This paper explores the concept of women growing older ‘solo’ by which we mean women who find themselves non partnered and ageing without children as they move into later life. We report on the findings from a mixed-methods survey of 76 solo women in the UK aged 50 years and over, used to provide a broader overview of the issues and challenges they face as they move into later life. Qualitative data from the survey captured respondents’ perspectives about the links between their relationships status and wellbeing in later life and highlighted specific cumulative disadvantages emerging for some women as a result of their solo lifestyles. We discuss two key themes were identified; ‘solo-loneliness’ and ‘meaningful futures’ in conjunction with the relevant literature and make suggestions for future research within gender and ageing studies that could enhance more positive approaches to solo lifestyles