Variations on the Vev Flip-Flop: Instantaneous Freeze-out and Decaying Dark Matter

In this work we consider a simple model for dark matter and identify regions of parameter space where the relic abundance is set via kinematic thresholds, which open and close due to thermal effects. We discuss instantaneous freeze-out, where dark matter suddenly freezes-out when the channel connecting dark matter to the thermal bath closes, and decaying dark matter, where dark matter freezes-out while relativistic and later decays when a kinematic threshold temporarily opens. These mechanisms can occur in the vicinity of a one-step or a two-step phase transition. In all cases thermal effects provide this dynamic behaviour, while ensuring that dark matter remains stable until the present day.Comment: 23 pages, 13 figures; v2: version matched to journal (JHEP), added a detailed discussion of further two-to-two processe

Dynamic Freeze-In: Impact of Thermal Masses and Cosmological Phase Transitions on Dark Matter Production

The cosmological abundance of dark matter can be significantly influenced by the temperature dependence of particle masses and vacuum expectation values. We illustrate this point in three simple freeze-in models. The first one, which we call kinematically induced freeze-in, is based on the observation that the effective mass of a scalar temporarily becomes very small as the scalar potential undergoes a second order phase transition. This opens dark matter production channels that are otherwise forbidden. The second model we consider, dubbed vev-induced freeze-in, is a fermionic Higgs portal scenario. Its scalar sector is augmented compared to the Standard Model by an additional scalar singlet, $S$, which couples to dark matter and temporarily acquires a vacuum expectation value (a two-step phase transition or `vev flip-flop'). While $\langle S \rangle \neq 0$, the modified coupling structure in the scalar sector implies that dark matter production is significantly enhanced compared to the $\langle S \rangle = 0$ phases realised at very early times and again today. The third model, which we call mixing-induced freeze-in, is similar in spirit, but here it is the mixing of dark sector fermions, induced by non-zero $\langle S \rangle$, that temporarily boosts the dark matter production rate. For all three scenarios, we carefully dissect the evolution of the dark sector in the early Universe. We compute the DM relic abundance as a function of the model parameters, emphasising the importance of thermal corrections and the proper treatment of phase transitions in the calculation.Comment: 26 pages, 11 figures, v2: matches journal version, change to the value of a benchmark coupling in section II, impact of thermal masses increase

Searching for physics beyond the Standard Model in an off-axis DUNE near detector

Next generation neutrino oscillation experiments like DUNE and T2HK are multi-purpose observatories, with a rich physics program beyond oscillation measurements. A special role is played by their near detector facilities, which are particularly well-suited to search for weakly coupled dark sector particles produced in the primary target. In this paper, we demonstrate this by estimating the sensitivity of the DUNE near detectors to the scattering of sub-GeV DM particles and to the decay of sub-GeV sterile neutrinos (“heavy neutral leptons”). We discuss in particular the importance of the DUNE-PRISM design, which allows some of the near detectors to be moved away from the beam axis. At such off-axis locations, the signal-to-background ratio improves for many new physics searches. We find that this leads to a dramatic boost in the sensitivity to boosted DM particles interacting mainly with hadrons, while for boosted DM interacting with leptons, data taken on-axis leads to marginally stronger exclusion limits. Searches for heavy neutral leptons perform equally well in both configurations

Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A

AbstractBackground: The CDKN2/INK4A tumour suppressor gene is deleted or mutated in a large number of human cancers. Overexpression of its product, p16, has been shown to block the transition through the G1/S phase of the cell cycle in a pRb-dependent fashion by inhibiting the cyclin D-dependent kinases cdk4 and cdk6. Reconstitution of p16 function in transformed cells is therefore an attractive target for anti-cancer drug design.Results We have identified a 20-residue synthetic peptide — corresponding to amino acids 84–103 of p16 – that interacts with cdk4 and cdk6, and inhibits the in vitro phosphorylation of pRb mediated by cdk4–cyclin D1. The amino-acid residues of p16 important for its interaction with cdk4 and cdk6 and for the inhibition of pRb phosphorylation were defined by an alanine substitution series of peptides. In normal proliferating human HaCaT cells and in cells released from serum starvation, entry into S phase was blocked by the p16-derived peptide when it was coupled to a small peptide carrier molecule and applied directly to the tissue culture medium. This cell-cycle block was associated with an inhibition of pRb phosphorylation in vivo.Conclusion These results demonstrate that a p16-derived peptide can mediate three of the known functions of p16: firstly, it interacts with cdk4 and cdk6; secondly, it inhibits pRb phosphorylation in vitro and in vivo; and thirdly, it blocks entry into S phase. The fact that one small synthetic peptide can enter the cells directly from the tissue culture medium to inhibit pRb phosphorylation and block cell-cycle progression makes this an attractive approach for future peptidometic drug design. Our results suggest a novel and exciting means by which the function of the p16 suppressor gene can be restored in human tumours

Loss of functional pRB is not a ubiquitous feature of B-cell malignancies

Human cancers frequently sustain genetic mutations that alter the function of their G1 cell cycle control check point. These include changes to the retinoblastoma gene and to the genes that regulate its phosphorylation, such as the cyclin-dependent kinase inhibitor p16(INK4a). Altered expression of retinoblastoma protein (pRb) is associated with non-Hodgkin's lymphoma, particularly centroblastic and Burkitt's lymphomas. pRb is expressed in normal B-cells and its regulatory phosphorylation pathway is activated in response to a variety of stimuli. Since human B-lymphoma-derived cell lines are often used as in vitro model systems to analyse the downstream effects of signal transduction, we examined the functional status of pRb in a panel of human B-cell lines. We identified eleven cell lines which express the hyperphosphorylated forms of pRb. Furthermore, we suggest that the pRb protein appears to be functional in these cell lines

Mechanism-Based Screen Establishes Signalling Framework for DNA Damage-Associated G1 Checkpoint Response

DNA damage activates checkpoint controls which block progression of cells through the division cycle. Several different checkpoints exist that control transit at different positions in the cell cycle. A role for checkpoint activation in providing resistance of cells to genotoxic anticancer therapy, including chemotherapy and ionizing radiation, is widely recognized. Although the core molecular functions that execute different damage activated checkpoints are known, the signals that control checkpoint activation are far from understood. We used a kinome-spanning RNA interference screen to delineate signalling required for radiation-mediated retinoblastoma protein activation, the recognized executor of G1 checkpoint control. Our results corroborate the involvement of the p53 tumour suppressor (TP53) and its downstream targets p21CIP1/WAF1 but infer lack of involvement of canonical double strand break (DSB) recognition known for its role in activating TP53 in damaged cells. Instead our results predict signalling involving the known TP53 phosphorylating kinase PRPK/TP53RK and the JNK/p38MAPK activating kinase STK4/MST1, both hitherto unrecognised for their contribution to DNA damage G1 checkpoint signalling. Our results further predict a network topology whereby induction of p21CIP1/WAF1 is required but not sufficient to elicit checkpoint activation. Our experiments document a role of the kinases identified in radiation protection proposing their pharmacological inhibition as a potential strategy to increase radiation sensitivity in proliferating cancer cells

Report from Working Group 3: Beyond the standard model physics at the HL-LHC and HE-LHC

This is the third out of five chapters of the final report [1] of the Workshop on Physics at HL-LHC, and perspectives on HE-LHC [2]. It is devoted to the study of the potential, in the search for Beyond the Standard Model (BSM) physics, of the High Luminosity (HL) phase of the LHC, defined as $3$ ab$^{-1}$ of data taken at a centre-of-mass energy of 14 TeV, and of a possible future upgrade, the High Energy (HE) LHC, defined as $15$ ab$^{-1}$ of data at a centre-of-mass energy of 27 TeV. We consider a large variety of new physics models, both in a simplified model fashion and in a more model-dependent one. A long list of contributions from the theory and experimental (ATLAS, CMS, LHCb) communities have been collected and merged together to give a complete, wide, and consistent view of future prospects for BSM physics at the considered colliders. On top of the usual standard candles, such as supersymmetric simplified models and resonances, considered for the evaluation of future collider potentials, this report contains results on dark matter and dark sectors, long lived particles, leptoquarks, sterile neutrinos, axion-like particles, heavy scalars, vector-like quarks, and more. Particular attention is placed, especially in the study of the HL-LHC prospects, to the detector upgrades, the assessment of the future systematic uncertainties, and new experimental techniques. The general conclusion is that the HL-LHC, on top of allowing to extend the present LHC mass and coupling reach by $20-50\%$ on most new physics scenarios, will also be able to constrain, and potentially discover, new physics that is presently unconstrained. Moreover, compared to the HL-LHC, the reach in most observables will, generally more than double at the HE-LHC, which may represent a good candidate future facility for a final test of TeV-scale new physics

Variations on the Vev Flip-Flop: Instantaneous Freeze-out and Decaying Dark Matter

In this work we consider a simple model for dark matter and identify regions of parameter space where the relic abundance is set via kinematic thresholds, which open and close due to thermal effects. We discuss instantaneous freeze-out, where dark matter suddenly freezes-out when the channel connecting dark matter to the thermal bath closes, and decaying dark matter, where dark matter freezes-out while relativistic and later decays when a kinematic threshold temporarily opens. These mechanisms can occur in the vicinity of a one-step or a two-step phase transition. In all cases thermal effects provide this dynamic behaviour, while ensuring that dark matter remains stable until the present day