Four-Quark Effective Operators at Hadron Colliders

The robustness of translating effective operator constraints to BSM theories crucially depends on the mass and coupling of BSM particles. This is especially relevant for hadron colliders where the partonic centre of mass energy is around the typical energy scales of natural BSM theories. The caveats in applying the limits are discussed using Z' and G' models, illustrating the effects for a large class of models. This analysis shows that the applicability of effective operators mainly depends on the ratio of the transfer energy in the events and the mass scale of the full theory. Moreover, based on these results a method is developed to recast existing experimental limits on four-quark effective operators to the full theory parameter space.Comment: 28 pages, 10 figures, version 2 updated to JHEP 03 (2015) 09

Cornering Colored Coannihilation

In thermal dark matter models, allowing the dark matter candidate to coannihilate with another particle can considerably loosen the relic density constraints on the dark matter mass. In particular, introducing a single strongly interacting coannihilation partner in a dark matter model can bring the upper bound on the dark sector energy scale from a few TeV up to about 10 TeV. While these energies are outside the LHC reach, a large part of the parameter space for such coannihilating models can be explored by future hadron colliders. In this context, it is essential to determine whether the current bounds on dark matter simplified models also hold in non-minimal scenarios. In this paper, we study extended models that include multiple coannihilation partners. We show that the relic density bounds on the dark matter mass in these scenarios are stronger than for the minimal models in most of the parameter space and that weakening these bounds requires sizable interactions between the different species of coannihilation partners. Furthermore, we discuss how these new interactions as well as the additional particles in the models can lead to stronger collider bounds, notably in jets plus missing transverse energy searches. This study serves as a vital ingredient towards the determination of the highest possible energy scale for thermal dark matter models.Comment: 47 pages, 12 figure

Littlest Higgs with T-parity: Status and Prospects

The Littlest Higgs model with T-parity is providing an attractive solution to the fine-tuning problem. This solution is only entirely natural if its intrinsic symmetry breaking scale f is relatively close to the electroweak scale. We examine the constraints using the latest results from the 8 TeV run at the LHC. Both direct searches and Higgs precision physics are taken into account. The constraints from Higgs couplings are by now competing with electroweak precision tests and both combined exclude f up to 694 GeV or 560 GeV depending on the implementation of the down-type Yukawa sector. Direct searches provide robust and complementary limits and constrain f to be larger than 638 GeV. We show that the Littlest Higgs model parameter space is slowly driven into the TeV range. Furthermore, we develop a strategy on how to optimise present supersymmetry searches for the considered model, with the goal to improve the constraints and yield more stringent limits on f.Comment: 43 pages, 16 figures, version 2 updated to JHEP 02 (2014) 05

Simplified Phenomenology for Colored Dark Sectors

We perform a general study of the relic density and LHC constraints on simplified models where the dark matter coannihilates with a strongly interacting particle X. In these models, the dark matter depletion is driven by the self-annihilation of X to pairs of quarks and gluons through the strong interaction. The phenomenology of these scenarios therefore only depends on the dark matter mass and the mass splitting between dark matter and X as well as the quantum numbers of X. In this paper, we consider simplified models where X can be either a scalar, a fermion or a vector, as well as a color triplet, sextet or octet. We compute the dark matter relic density constraints taking into account Sommerfeld corrections and bound state formation. Furthermore, we examine the restrictions from thermal equilibrium, the lifetime of X and the current and future LHC bounds on X pair production. All constraints are comprehensively presented in the mass splitting versus dark matter mass plane. While the relic density constraints can lead to upper bounds on the dark matter mass ranging from 2 TeV to more than 10 TeV across our models, the prospective LHC bounds range from 800 to 1500 GeV. A full coverage of the strongly coannihilating dark matter parameter space would therefore require hadron colliders with significantly higher center of mass energies.Comment: 34 pages, 8 figures, matches JHEP versio

Hunting for Dark Matter Coannihilation by Mixing Dijet Resonances and Missing Transverse Energy

Simplified models of the dark matter (co)annihilation mechanism predict striking new collider signatures untested by current searches. These models, which were codified in the coannihilation codex, provide the basis for a dark matter (DM) discovery program at the Large Hadron Collider (LHC) driven by the measured DM relic density. In this work, we study an exemplary model featuring $s$-channel DM coannihilation through a scalar diquark mediator as a representative case study of scenarios with strongly interacting coannihilation partners. We discuss the full phenomenology of the model, ranging from low energy flavor constraints, vacuum stability requirements, and precision Higgs effects to direct detection and indirect detection prospects. Moreover, motivated by the relic density calculation, we find significant portions of parameter space are compatible with current collider constraints and can be probed by future searches, including a proposed analysis for the novel signature of a dijet resonance accompanied by missing transverse energy (MET). Our results show that the $13$ TeV LHC with $100~\mathrm{fb}^{-1}$ luminosity should be sensitive to mediators as heavy as 1 TeV and dark matter in the 400--500 GeV range. The combination of searches for single and paired dijet peaks, non-resonant jets + MET excesses, and our novel resonant dijet + MET signature have strong coverage of the motivated relic density region, reflecting the tight connections between particles determining the dark matter abundance and their experimental signatures at the LHC.Comment: 35 pages, 9 figure

Seasonal coronavirus infections trigger NLRP3 inflammasome activation in macrophages but is therapeutically targetable

Seasonal coronaviruses widely circulate in the global population, and severe complications can occur in specific vulnerable populations. Little is known on their pathogenic mechanisms and no approved treatment is available. Here, we present anecdotal evidence that the level of IL-1β, a hallmark of inflammasome activation, appears elevated in a subset of seasonal coronavirus infected patients. We found that cultured human macrophages support the full life cycle of three cultivatable seasonal coronaviruses. Their infections effectively activate NLRP3 inflammasome activation through TLR4 ligation and NF-κB activation. This activation can be attenuated by specific pharmacological inhibitors and clinically used medications including dexamethasone and flufenamic acid. Interestingly, combination of antiviral and anti-inflammatory drugs simultaneously inhibit seasonal coronavirus-triggered inflammatory response and viral replication. Collectively, these findings show that the TLR4/NF-κB/NLRP3 axis drives seasonal coronavirus triggered-inflammatory response, which in turn represents a viable therapeutic target.</p

Clinical Features, Antiviral Treatment, and Patient Outcomes:A Systematic Review and Comparative Analysis of the Previous and the 2022 Mpox Outbreaks

Background:This study aims to comparatively analyze clinical features, treatment, and patient outcomes between the previous and the 2022 mpox (monkeypox) outbreaks. Methods:Five bibliographic databases were searched for studies reporting clinical features, management, and patient outcomes of mpox. Systematic review and meta-analysis were performed. Results:In total, 73 studies were included in the systematic review, of which 33 studies were subjected to meta-analysis. Previous outbreaks substantially affected children, whereas the 2022 outbreak primarily affected male adults, of which 94.66% (95% confidence interval [CI], 88.03–98.95) were men who have sex with men. Furthermore, 72.47% (95% CI, 51.04–89.71) reported high-risk sexual activity and the overall human immunodeficiency virus (HIV) prevalence was 37.65% (95% CI, 30.09–45.50). Skin lesions remain the typical symptom; however, their anatomic distribution differed. Systemic manifestations were common, but rectal pain was unique to the 2022 outbreak. The estimated overall fatality during past outbreaks in Africa was 4.61% (95% CI, 2.39%–7.35%), whereas 6.34% (95% CI, 3.35%–10.10%) of patients from the 2022 outbreak required hospitalization. Antiviral treatment, in particular tecovirimat, has been prescribed for a subset of patients, but the efficacy remains inconclusive.Conclusions:These findings are important for better understanding the disease and guiding adequate response to mpox outbreaks.</p

Modulation of Indoleamine 2,3-Dioxygenase 1 During Inflammatory Bowel Disease Activity in Humans and Mice

Background and Aims: Indoleamine 2,3 dioxygenase-1 (IDO1), a key enzyme in tryptophan metabolism, is strongly up-regulated both in human inflammatory bowel disease (IBD) and animal models of colitis, however its role in the pathogenesis is still controversial. In this study, we investigated IDO1 expression and activity in a mouse model of DSS-induced chronic colitis as well as in colon biopsies and sera from IBD patients. Methods: Chronic colitis was induced in mice through the oral administration of dextran sodium sulfate (DSS), and IDO1 activity was induced by i.p. treatment with N-acetyl serotonin (NAS). IDO1 expression and catalytic activity (measured as Kyn/Trp ratio) was evaluated in sera and tissue samples collected from mice and 93 IBD patients under immunotherapy with Vedolizumab (VDZ) or Ustekinumab (UST). Results: Strong up-regulation of IDO1 was found in colons of mice with acute colitis, which follows disease activity. Enhanced IDO1 activity by NAS treatment protects the intestinal mucosa during the recovery phase of chronic colitis. In IBD patients, IDO1 expression and activity correlate with the severity of mucosal inflammation with inflamed regions showing higher IDO1 expression compared to non-inflamed regions within the same patient. Endoscopic response to VDZ/UST treatment is associated with decreased expression of IDO1. Conclusions: This is the first study demonstrating immunomodulatory activity of IDO1 in a chronic mouse model of DSS-induced colitis. As its expression and catalytic activity correlate with the grade of mucosal inflammation and treatment response, IDO1 could represent a promising biomarker for disease severity and treatment monitoring in IBD.</p

Modulation of Human Peripheral Blood Mononuclear Cell Signaling by Medicinal Cannabinoids

Medical marijuana is increasingly prescribed as an analgesic for a growing number of indications, amongst which terminal cancer and multiple sclerosis. However, the mechanistic aspects and properties of cannabis remain remarkably poorly characterized. In this study we aimed to investigate the immune-cell modulatory properties of medical cannabis. Healthy volunteers were asked to ingest medical cannabis, and kinome profiling was used to generate comprehensive descriptions of the cannabis challenge on inflammatory signal transduction in the peripheral blood of these volunteers. Results were related to both short term and long term effects in patients experimentally treated with a medical marijuana preparation for suffering from abdominal pain as a result of chronic pancreatitis or other causes. The results reveal an immunosuppressive effect of cannabinoid preparations via deactivation of signaling through the pro-inflammatory p38 MAP kinase and mTOR pathways and a concomitant deactivation of the pro-mitogenic ERK pathway. However, long term cannabis exposure in two patients resulted in reversal of this effect. While these data provide a powerful mechanistic rationale for the clinical use of medical marijuana in inflammatory and oncological disease, caution may be advised with sustained use of such preparations