Light Stop Searches at the LHC in Events with two b-Jets and Missing Energy

We propose a new method to discover light top squarks (stops) in the co-annihilation region at the Large Hadron Collider (LHC). The bino-like neutralino is the lightest supersymmetric particle (LSP) and the lighter stop is the next-to-LSP. Such scenarios can be consistent with electroweak baryogenesis and also with dark matter constraints. We consider the production of two stops in association with two b-quarks, including pure QCD as well as mixed electroweak-QCD contributions. The stops decay into a charm quark and the LSP. For a higgsino-like light chargino the electroweak contributions can exceed the pure QCD prediction. We show the size of the electroweak contributions as a function of the stop mass and present the LHC discovery reach in the stop-neutralino mass plane.Comment: 12 pages, 10 figure

Hadronic production of bottom-squark pairs with electroweak contributions

We present the complete computation of the tree-level and the next-to-leading order electroweak contributions to bottom-squark pair production at the LHC. The computation is performed within the minimal supersymmetric extension of the Standard Model. We discuss the numerical impact of these contributions in several supersymmetric scenarios.Comment: 33 pages, v2: preprint numbers correcte

Constraints on supersymmetry with light third family from LHC data

We present a re-interpretation of the recent ATLAS limits on supersymmetry in channels with jets (with and without b-tags) and missing energy, in the context of light third family squarks, while the first two squark families are inaccessible at the 7 TeV run of the Large Hadron Collider (LHC). In contrast to interpretations in terms of the high-scale based constrained minimal supersymmetric standard model (CMSSM), we primarily use the low-scale parametrisation of the phenomenological MSSM (pMSSM), and translate the limits in terms of physical masses of the third family squarks. Side by side, we also investigate the limits in terms of high-scale scalar non-universality, both with and without low-mass sleptons. Our conclusion is that the limits based on 0-lepton channels are not altered by the mass-scale of sleptons, and can be considered more or less model-independent.Comment: 20 pages, 8 figures, 2 tables. Version published in JHE

B and T cell acute lymphoblastic leukemia evade chemotherapy at distinct sites in the bone marrow

Persistence of residual disease after induction chemotherapy is a strong predictor of relapse in acute lymphoblastic leukemia (ALL). The bone marrow microenvironment may support treatment escape. Using 3D fluorescence imaging of 10 primary ALL xenografts we identify sites of predilection in the bone marrow for resistance to induction with dexamethasone, vincristine and doxorubicin. We detect B-cell precursor ALL cells predominantly in the perisinusoidal space at early engraftment and after chemotherapy. The spatial distribution of T-ALL cells was more widespread with contacts to endosteum, nestin+ pericytes and sinusoids. Dispersion of T-ALL cells in the bone marrow increased under chemotherapeutic pressure. A subset of slowly dividing ALL cells was transiently detected upon short-term chemotherapy, but not at residual disease after chemotherapy, challenging the notion that ALL cells escape treatment by direct induction of a dormant state in the niche. These lineage-dependent differences point to niche interactions that may be more specifically exploitable to improve treatment

SUSY parameter determination at the LHC using cross sections and kinematic edges

We study the determination of supersymmetric parameters at the LHC from a global fit including cross sections and edges of kinematic distributions. For illustration, we focus on a minimal supergravity scenario and discuss how well it can be constrained at the LHC operating at 7 and 14 TeV collision energy, respectively. We find that the inclusion of cross sections greatly improves the accuracy of the SUSY parameter determination, and allows to reliably extract model parameters even in the initial phase of LHC data taking with 7 TeV collision energy and 1/fb integrated luminosity. Moreover, cross section information may be essential to study more general scenarios, such as those with non-universal gaugino masses, and distinguish them from minimal, universal, models.Comment: 22 pages, 8 figure

Repurposing anthelmintic agents to eradicate resistant leukemia

Despite rapid progress in genomic profiling in acute lymphoblastic leukemia (ALL), identification of actionable targets and prediction of response to drugs remains challenging. To identify specific vulnerabilities in ALL, we performed a drug screen using primary human ALL samples cultured in a model of the bone marrow microenvironment combined with high content image analysis. Among the 2487 FDA-approved compounds tested, anthelmintic agents of the class of macrocyclic lactones exhibited potent anti-leukemia activity, similar to the already known anti-leukemia agents currently used in induction chemotherapy. Ex vivo validation in 55 primary ALL samples of both precursor B cell and T-ALL including refractory relapse cases confirmed strong anti-leukemia activity with IC50 values in the low micromolar range. Anthelmintic agents increased intracellular chloride levels in primary leukemia cells, inducing mitochondrial outer membrane depolarization and cell death. Supporting the notion that simultaneously targeting cell death machineries at different angles may enhance the cell death response, combination of anthelmintic agents with the BCL-2 antagonist navitoclax or with the chemotherapeutic agent dexamethasone showed synergistic activity in primary ALL. These data reveal anti-leukemia activity of anthelmintic agents and support exploiting drug repurposing strategies to identify so far unrecognized anti-cancer agents with potential to eradicate even refractory leukemia

Higgs boson enhancement effects on squark-pair production at the LHC

We study the Higgs boson effects on third-generation squark-pair production in proton-proton collision at the CERN Large Hadron Collider (LHC), including \Stop \Stop^*, \Stop\Sbot^*, and \Sbot \Sbot^*. We found that substantial enhancement can be obtained through s-channel exchanges of Higgs bosons at large $\tan\beta$, at which the enhancement mainly comes from $b\bar b$, $b\bar c$, and $c\bar b$ initial states. We compute the complete set of electroweak (EW) contributions to all production channels. This completes previous computations in the literature. We found that the EW contributions can be significant and can reach up to 25% in more general scenarios and at the resonance of the heavy Higgs boson. The size of Higgs enhancement is comparable or even higher than the PDF uncertainties and so must be included in any reliable analysis. A full analytical computation of all the EW contributions is presented.Comment: 23 pages, 7 figures, 1 tabl

Light Stop Decay in the MSSM with Minimal Flavour Violation

In supersymmetric scenarios with a light stop particle $\tilde{t}_1$ and a small mass difference to the lightest supersymmetric particle (LSP) assumed to be the lightest neutralino, the flavour changing neutral current decay $\tilde{t}_1 \to c \tilde{\chi}_1^0$ can be the dominant decay channel and can exceed the four-body stop decay for certain parameter values. In the framework of Minimal Flavour Violation (MFV) this decay is CKM-suppressed, thus inducing long stop lifetimes. Stop decay length measurements at the LHC can then be exploited to test models with minimal flavour breaking through Standard Model Yukawa couplings. The decay width has been given some time ago by an approximate formula, which takes into account the leading logarithms of the MFV scale. In this paper we calculate the exact one-loop decay width in the framework of MFV. The comparison with the approximate result exhibits deviations of the order of 10% for large MFV scales due to the neglected non-logarithmic terms in the approximate decay formula. The difference in the branching ratios is negligible. The large logarithms have to be resummed. The resummation is performed by the solution of the renormalization group equations. The comparison of the exact one-loop result and the tree level flavour changing neutral current decay, which incorporates the resummed logarithms, demonstrates that the resummation effects are important and should be taken into account.Comment: 29 page

Functional analysis of structural variants in single cells using Strand-seq

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones. We discovered distinct SV subclones with dysregulated Wnt signaling in a chronic lymphocytic leukemia patient. We further uncovered the consequences of subclonal chromothripsis in T cell acute lymphoblastic leukemia, which revealed c-Myb activation, enrichment of a primitive cell state and informed successful targeting of the subclone in cell culture, using a Notch inhibitor. By directly linking SVs to their functional effects, scNOVA enables systematic single-cell multiomic studies of structural variation in heterogeneous cell populations

CP asymmetries in the supersymmetric trilepton signal at the LHC

In the CP-violating Minimal Supersymmetric Standard Model, we study the production of a neutralino-chargino pair at the LHC. For their decays into three leptons, we analyze CP asymmetries which are sensitive to the CP phases of the neutralino and chargino sector. We present analytical formulas for the entire production and decay process, and identify the CP-violating contributions in the spin correlation terms. This allows us to define the optimal CP asymmetries. We present a detailed numerical analysis of the cross sections, branching ratios, and the CP observables. For light neutralinos, charginos, and squarks, the asymmetries can reach several 10%. We estimate the discovery potential for the LHC to observe CP violation in the trilepton channel.Comment: 39 pages, 8 figures, version to appear in EPJC, discussion(s) added, typo in (D.79), (D.118) corrected, new Fig. 7; The European Physical Journal C, Volume 72, Issue 3, 201