Adjuvant Properties of Thermal Component of Hyperthermia Enhanced Transdermal Immunization: Effect on Dendritic Cells

Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential

Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b Pathways

Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which methylsulfonylmethane (MSM) inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. We confirmed that MSM significantly decreased the relative luciferase activities indicating crosstalk between STAT5b/IGF-1R, STAT5b/HSP90α, and STAT3/VEGF. To confirm these findings in vivo, xenografts were established in Balb/c athymic nude mice with MDA-MB 231 cells and MSM was administered for 30 days. Concurring to our in vitro analysis, these xenografts showed decreased expression of STAT3, STAT5b, IGF-1R and VEGF. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers

Measurement of the Higgs boson production via vector boson fusion and its decay into bottom quarks in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2308.01253v2 [hep-ex], https://arxiv.org/abs/2308.01253v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-22-009 (CMS Public Pages). Report number: CMS-HIG-22-009, CERN-EP-2023-110.A measurement of the Higgs boson (H) production via vector boson fusion (VBF) and its decay into a bottom quark-antiquark pair (bb¯) is presented using proton-proton collision data recorded by the CMS experiment at s√ = 13 TeV and corresponding to an integrated luminosity of 90.8 fb−1. Treating the gluon-gluon fusion process as a background and constraining its rate to the value expected in the standard model (SM) within uncertainties, the signal strength of the VBF process, defined as the ratio of the observed signal rate to that predicted by the SM, is measured to be μqqHHbb¯ = 1.01 +0.55−0.46. The VBF signal is observed with a significance of 2.4 standard deviations relative to the background prediction, while the expected significance is 2.7 standard deviations. Considering inclusive Higgs boson production and decay into bottom quarks, the signal strength is measured to be μincl.Hbb¯ = 0.99 +0.48−0.41, corresponding to an observed (expected) significance of 2.6 (2.9) standard deviations.SCOAP3, STFC; Marie-Curie program and the European Research Council and Horizon 2020 Gran

Search for direct production of GeV-scale resonances decaying to a pair of muons in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2309.16003v2 [hep-ex], https://arxiv.org/abs/2309.16003v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including additional supplementary figures, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-005 (CMS Public Pages). Report number: CMS-EXO-21-005, CERN-EP-2023-165.A search for direct production of low-mass dimuon resonances is performed using s√ = 13 TeV proton-proton collision data collected by the CMS experiment during the 2017-2018 operation of the CERN LHC with an integrated luminosity of 96.6 fb−1. The search exploits a dedicated high-rate trigger stream that records events with two muons with transverse momenta as low as 3 GeV but does not include the full event information. The search is performed by looking for narrow peaks in the dimuon mass spectrum in the ranges of 1.1-2.6 GeV and 4.2-7.9 GeV. No significant excess of events above the expectation from the standard model background is observed. Model-independent limits on production rates of dimuon resonances within the experimental fiducial acceptance are set. Competitive or world's best limits are set at 90% confidence level for a minimal dark photon model and for a scenario with two Higgs doublets and an extra complex scalar singlet (2HDM+S). Values of the squared kinetic mixing coefficient ε2 in the dark photon model above 10−6 are excluded over most of the mass range of the search. In the 2HDM+S, values of the mixing angle sin(θH) above 0.08 are excluded over most of the mass range of the search with a fixed ratio of the Higgs doublets vacuum expectation tanβ = 0.5.SCOAP3

Search for W′ bosons decaying to a top and a bottom quark in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2310.19893v1 [hep-ex], https://arxiv.org/abs/2310.19893v1 . Comments: Submitted to the Journal of High Energy Physics. All figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/B2G-20-012 (CMS Public Pages). Report number: CMS-B2G-20-012, CERN-EP-2023-213.A search for W' bosons decaying to a top and a bottom quark in final states including an electron or a muon is performed with the CMS detector at the LHC. The analyzed data correspond to an integrated luminosity of 138 fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 Tev. Good agreement with the standard model expectation is observed and no evidence for the existence of the W' boson is found over the mass range examined. The largest observed deviation from the standard model expectation is found for a W' boson mass (mW′) hypothesis of 3.8 TeV with a relative decay width of 1%, with a local (global) significance of 2.6 (2.0) standard deviations. Upper limits on the production cross sections of W' bosons decaying to a top and a bottom quark are set. Left- and right-handed W' bosons with mW′ below 3.9 and 4.3 TeV, respectively, are excluded at the 95% confidence level, under the assumption that the new particle has a narrow decay width. Limits are also set for relative decay widths up to 30%. These are the most stringent limits to date on this W' boson decay channel.SCOAP3

Search for dark matter particles in W+W− events with transverse momentum imbalance in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2310.12229v2 [hep-ex], https://arxiv.org/abs/2310.12229v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-012 (CMS Public Pages).A search for dark matter particles is performed using events with a pair of W bosons and large missing transverse momentum. Candidate events are selected by requiring one or two leptons (ℓ = electrons or muons). The analysis is based on proton-proton collision data collected at a center-of-mass energy of 13 TeV by the CMS experiment at the LHC and corresponding to an integrated luminosity of 138 fb−1. No significant excess over the expected standard model background is observed in the ℓνqq and 2ℓ2ν final states of the W+W− boson pair. Limits are set on dark matter production in the context of a simplified dark Higgs model, with a dark Higgs boson mass above the W+W− mass threshold. The dark matter phase space is probed in the mass range 100–300 GeV, extending the scope of previous searches. Current exclusion limits are improved in the range of dark Higgs masses from 160 to 250 GeV, for a dark matter mass of 200 GeV.SCOAP3

Search for physics beyond the standard model in top quark production with additional leptons in the context of effective field theory

A preprint version of the article is available at arXiv:2307.15761v2 [hep-ex], https://arxiv.org/abs/2307.15761v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-006 (CMS Public Pages). Report number: CMS-TOP-22-006, CERN-EP-2023-124.A search for new physics in top quark production with additional final-state leptons is performed using data collected by the CMS experiment in proton-proton collisions at √s = 13 TeV at the LHC during 2016-2018. The data set corresponds to an integrated luminosity of 138 fb−1. Using the framework of effective field theory (EFT), potential new physics effects are parametrized in terms of 26 dimension-six EFT operators. The impacts of EFT operators are incorporated through the event-level reweighting of Monte Carlo simulations, which allows for detector-level predictions. The events are divided into several categories based on lepton multiplicity, total lepton charge, jet multiplicity, and b-tagged jet multiplicity. Kinematic variables corresponding to the transverse momentum (pT) of the leading pair of leptons and/or jets as well as the pT of on-shell Z bosons are used to extract the 95% confidence intervals of the 26 Wilson coefficients corresponding to these EFT operators. No significant deviation with respect to the standard model prediction is found.SCOAP3

Managing climatic risks to combat land degradation and enhance food security: key information needs

This paper discusses the key information needs to reduce the negative impacts of weather variability and climate change on land degradation and food security, and identifies the opportunities and barriers between the information and services needed. It suggests that vulnerability assessments based on a livelihood concept that includes climate information and key socio-economic variables can overcome the narrow focus of common one-dimensional vulnerability studies. Both current and future climatic risks can be managed better if there is appropriate policy and institutional support together with technological interventions to address the complexities of multiple risks that agriculture has to face. This would require effective partnerships among agencies dealing with meteorological and hydrological services, agricultural research, land degradation and food security issues. In addition a state-of-the-art infrastructure to measure, record, store and disseminate data on weather variables, and access to weather and seasonal climate forecasts at desired spatial and temporal scales would be needed