Top Partners Research Articles

Computational Approach Based on Independent Drug Action Identifies Clinically Relevant Combinations for Acute Myeloid Leukemia

Background Acute myeloid leukemia (AML) is clinically and genetically heterogenous due to complex co-mutation landscape. Combination therapy has shown effectiveness in overcoming tumor heterogeneity and acquired resistance across multiple cancers including AML. However, the discovery of novel combinations has traditionally relied on cell line-based measurements that often fail clinically due to inter- and intra-tumor heterogeneity of patients. To address this challenge of finding clinically relevant combination therapy for AML, we applied the independent drug action (IDA) principle (Palmer & Sorger, 2017) to computationally predict drug combinations using ex vivo monotherapy responses measured in primary AML patient specimens (n > 1000). Methods We utilized the ex vivo drug sensitivity testing (DST) of primary AML samples from three studies; 1. FPMTB (Malani et al. 2021), 164 patient responses to 515 single agents; 2. Beat-AML (Tyner et al. 2018), 579 patient responses to 166 single agents; 3. Oregon Health & Science University (OSHU), 596 patient responses to 51 single agents and 170 2-drug combinations (Figure 1A). To summarize the multiparametric dose-response relationship into a single metric, drug sensitivity score (DSS) (Yadav et al. 2014) was calculated from the dose-response cell viability data of the samples using the BREEZE pipeline (Potdar et al. 2020) to derive monotherapy efficacy. We modified IDACombo package (Ling & Huang, 2020) to predict the mean combination DSS of every pairwise combination. IDAComboscore was calculated for each predicted combination to determine if it is more efficacious than its constituent monotherapies. The top hits from predicted combinations were selected by filtering for combinations with mean DSS in the top 10 th percentile, and positive IDAComboscore. These combinations were then ranked in descending order of IDAComboscore. For validation, Spearman correlation was applied to compare the predicted DSS against ex vivo DST-derived DSS of 170 combinations from the OSHU dataset. Results By applying IDA-based prediction on FPMTB and Beat-AML datasets, we identified that the mean combination DSS exceeded monotherapy DSS (p < 2.2x10 -6, Wilcoxon rank-sum test), suggesting that the predicted combination would outperform monotherapy. After accounting for monotherapies that displayed pan-toxicity across healthy samples and primary AML samples (mean DSS > 95 th percentile), we found venetoclax as the top combination partner of the top 100 most effective predicted combinations (FPMTB, n = 33; Beat-AML, n = 35). We further interrogated the makeup of venetoclax-based combinations and found kinase inhibitors (PI3Ki, MEKi, mTORi), and epigenetic modifiers (BETi, HDACi) as common partners. A total of 8 (FPMTB) and 18 (Beat-AML) out of these 100 combinations were made of FDA-approved drugs (both partners). Next, we investigated the robustness of the predictions across 2 datasets, and we found 1767 overlapping combinations with a strong correlation between their predicted mean DSS (Spearman ρ = 0.74, p < 2.2x10 -6). We finally validated the performance of IDA predictions using ex vivo DST data of 170 unique combinations from 596 primary AML samples. We found that the predicted DSS values of the 170 combinations strongly correlated with the actual ex vivo DST-derived combination DSS (Spearman ρ = 0.76, p < 2.2x10 -6, Figure 1B). Using 75 th percentile of DSS distribution as effective combination cutoff, the approach showed an accuracy of 84.7%. We then asked if disease status of patients affected prediction accuracy and found that IDA approach successfully predicted effective combinations for patients at diagnosis as well as at relapse (diagnosis ρ = 0.74 vs relapse ρ = 0.73). Conclusion We have computationally identified and validated clinically actionable drug combinations for AML using ex vivo monotherapy responses from >1000 tumor specimens based on IDA principle. Irrespective of pharmacological interaction, IDA-based combinations are more efficacious than single drugs in AML primary tumors. Our approach enables the major advantage of identifying effective combinations for the entire patient population as an alternative to personalized combinations. Further associations with genetic makeup and transcriptomics signature can be leveraged to identify suitable combinations.

Hierarchy problem and the top Yukawa coupling: An alternative to top partner solutions

Hierarchy problem and the top Yukawa coupling: An alternative to top partner solutions

Sexually transmitted infection knowledge among men who have sex with men in Nairobi, Kenya.

High rates of sexually transmitted infections (STIs) among men who have sex with men (MSM) have been reported, but there is little research on their STI knowledge. Our study sought to determine participants' characteristics that contribute to either high or low STI knowledge among MSM in Nairobi, Kenya. We mobilized MSM aged ≥18 years from Nairobi into a cross-sectional study. To determine their understanding of STIs, a pre-tested structured questionnaire was administered. Knowledge score was generated by summing up the number of responses answered correctly by a participant. We dichotomized scores as "low" and "high", by splitting the group at <12 and ≥12 which was the mean. A total of 404 participants were interviewed between March and August 2020. The mean age was 25.2 (SD = 6.4) years. Majority were single (80.4%) and Christians (84.2%). All participants had some formal education ranging from primary to tertiary; the majority (92.3%) had secondary education or more. Most (64.0%) were employed and their monthly income ranged from <50->150 USD. Almost all (98.5%) were Kenyans. Of the 404 (90.6%) self-identified as male and (47.5%) reported to be exclusively top partners. Many (39.9%) reported being versatile, while those reporting to be bottom partners were, (12.6%). The last 12 months, (55.4%) of the participants reported having sex with men only and (88.6%) reported to have had multiple sexual partners. Participants scored an average of 12.2, SD 4.5. Multivariable backward elimination logistic regression revealed that participants who had tertiary education (aOR = 0.50, 95% CI 0.32-0.77), a higher income (aOR = 0.40, 95% CI 0.22-0.75) and were engaging in vaginal sex (aOR = 1.86, 95% CI 1.25-2.78) predicted significantly higher odds of high knowledge in the final multivariable model. Participant's knowledge level regarding STIs was low. We recommend health care workers to continue educating patients about STIs.

Dark top partner

Composite Higgs models with extended symmetries can feature mesonic dark matter candidates. In fundamental CHMs, the origin of dark parity can be explained in the UV theory. Combined with top partial compositeness, this leads to non-chiral Yukawa interaction connecting mesonic DM with one dark top partner and one SM top. We examine the DM phenomenology in SU(6)/SO(6) and SU(6)/Sp(6) CHMs with the presence of dark top partners. Phenomenological constraints require the mass of top partner in even parity to be of the multi-TeV order.

Search for pair-produced vector-like top and bottom partners in events with large missing transverse momentum in pp collisions with the ATLAS detector

A search for pair-produced vector-like quarks using events with exactly one lepton (e or mu ), at least four jets including at least one b-tagged jet, and large missing transverse momentum is presented. Data from proton–proton collisions at a centre-of-mass energy of sqrt{s}=13 text {TeV}, recorded by the ATLAS detector at the LHC from 2015 to 2018 and corresponding to an integrated luminosity of 139 fb^{-1}, are analysed. Vector-like partners T and B of the top and bottom quarks are considered, as is a vector-like X with charge +5/3, assuming their decay into a W, Z, or Higgs boson and a third-generation quark. No significant deviations from the Standard Model expectation are observed. Upper limits on the production cross-section of T and B quark pairs as a function of their mass are derived for various decay branching ratio scenarios. The strongest lower limits on the masses are 1.59 text {TeV} assuming mass-degenerate vector-like quarks and branching ratios corresponding to the weak-isospin doublet model, and 1.47 text {TeV} (1.46 text {TeV}) for exclusive T rightarrow Zt (B/X rightarrow Wt) decays. In addition, lower limits on the T and B quark masses are derived for all possible branching ratios.

Exploring maverick top partner decays at the LHC

In this work, we have considered an extension of the standard model (SM) with a $SU(2{)}_{L}$ singlet vectorlike quark (VLQ) with electric charge $Q=+2/3$. The model also contains an additional local $U(1{)}_{d}$ symmetry group and the corresponding gauge boson is the dark photon. The VLQ is charged while all the SM particles are neutral under the new $U(1{)}_{d}$ gauge group. Even though in this model the VLQ possesses many properties qualitatively similar to that of the traditional top partner (${T}_{p}$), there are some compelling differences as well. In particular, its branching ratio to the traditional modes (${T}_{p}\ensuremath{\rightarrow}bW,tZ,th$) are suppressed which in turn helps to evade many of the existing bounds, mainly coming from the LHC experiments. In an earlier work, such a VLQ is referred to as ``maverick top partner''. It has been shown that the top partner in this model predominantly decays to a top quark and a dark photon/dark Higgs pair (${T}_{p}\ensuremath{\rightarrow}t{\ensuremath{\gamma}}_{d},t{h}_{d}$) over a large region of the parameter space. The dark photon can be made invisible and consequently, it gives rise to the missing transverse energy (${\overline{)E}}_{T}$) signature at the LHC detector. We have mainly focused on the LHC signatures and future prospects of such top partners. In particular, we have studied the $t\overline{t}+{\overline{)E}}_{T}$ and $t+{\overline{)E}}_{T}$ signatures in the context of the LHC via pair and single productions of the top partner, respectively at 13 and 14 TeV LHC center of mass energies assuming that the dark photon either decays into an invisible mode or it is invisible at the length scale of the detector. We have shown that one can exclude $\mathrm{sin}{\ensuremath{\theta}}_{L}\ensuremath{\sim}0.025$ (0.05) for ${m}_{{T}_{p}}\ensuremath{\le}2.0\text{ }(2.6)\text{ }\text{ }\mathrm{TeV}$ at $\sqrt{s}=14\text{ }\text{ }\mathrm{TeV}$ with an integrated luminosity of $3\text{ }\text{ }{\mathrm{ab}}^{\ensuremath{-}1}$ using the single top partner production channel.

Pair production of the vectorlike top partner at the CLIC

New vectorlike T-quarks (VLQ-T) have been predicted in many scenarios of new physics beyond the Standard Model, the current mass exclusion limits from LHC experiments will be relaxed by the presence of additional decay channels. In this work, we investigate the prospect of discovering the pair production of VLQ-T at the future 3 TeV Compact Linear Collider (CLIC), by focusing on the final signals via the standard decay channel T→Wb where one of the W bosons decays leptonically and the other decays hadronically. By performing a rapid detector simulation of the signal and background events as well as considering the initial state radiation and beamstrahlung effects, the exclusion limit at the 95% confidence level and the 5σ discovery prospects are, respectively, obtained on the integrated luminosity and the branching ratio of T→Wb for three typical VLQ-T masses.

Higgs squared

We present a novel construction for a Higgs-VEV sensitive (HVS) operator, which can be used as a trigger operator in cosmic selection models for the electroweak hierarchy problem. Our operator does not contain any degrees of freedom charged under the SM gauge symmetries, leading to reduced tuning in the resulting models. Our construction is based on the extension of a two Higgs doublet model (2HDM) with a softly broken approximate global D8 symmetry (the symmetry group of a square). A cosmic crunching model based on our extended Higgs sector has only a percent level tuning corresponding to the usual little hierarchy problem. In large regions of parameter space the 2HDM is naturally pushed towards the alignment limit. A complete model requires the introduction of fermionic top partners to ensure the approximate D8 symmetry in the fermion sector. We also show that the same extended Higgs sector can be used for a novel implementation of the seesaw mechanism of neutrino masses.

Top partners and scalar dark matter: A nonminimal reappraisal

A large set of models beyond the Standard Model of particle physics suggest that the top quark plays a special role in fundamental interactions. At the same time some of these models predict that a particle responsible for dark matter is present in the physical spectrum of the theory, and in particular cases dark matter may be specially linked to the top sector. Such a new physics configuration occurs, for instance, in composite frameworks that additionally feature vector-like quarks as mediators of the interactions of the dark matter with the Standard Model. We investigate the interplay of top-philic dark matter and the presence of several vector-like top partners. Such a non-minimal setup with several vector-like fermions is typical of composite scenarios, and we make use of an effective model to study to which extent such non-minimality modifies the collider and cosmological phenomenology of the minimal model, the latter only including one vector-like mediator of the dark matter interactions with the Standard Model.

Correlating the CDF W-boson mass shift with the b → sℓ+ℓ− anomalies

The recently updated measurement of the W-boson mass by the CDF collaboration exhibits a 7σ deviation from the SM expectation, which may imply a sign of new physics beyond the SM. The observed discrepancy could be explained by new fermions that carry the electroweak gauge charges and affect the vacuum polarization of gauge bosons. Notably, if the new fermions also have the same quantum numbers as of the SM quarks, they can mix with the latter and thus modify the penguin diagrams governing the b→sℓ+ℓ− transitions. Therefore, the W-boson mass shift could be related to the b→sℓ+ℓ− anomalies observed by the LHCb collaboration during the past few years. To investigate this possibility, we consider in this letter a model containing a vector-like top partner gauged under a new U(1)′ symmetry. It is found that the latest CDF mW measurement and the b→sℓ+ℓ− anomalies can be simultaneously accommodated at 2σ level.

India- Sri Lanka Trade Relations Post ISFTA: An Empirical Analysis

India has traditionally been one of Sri Lanka's greatest trading partners, and Sri Lanka continues to be one of India's top trade partners in the SAARC region. The bilateral trade between India and Sri Lanka has got a big boost after the implementation of ISFTA. The present study found that a robust trade flow between Indo-Sri Lanka with the signing of ISFTA, a major portion of India's exports to Sri Lanka went through the Sri Lankan negative list, while a significant portion of Sri Lanka's exports to India proceeded through the concession-offered route. The concessions provided to Sri Lanka improved access to the Indian market, the opposite was not true for India's exports to Sri Lanka.

Estimating the size of Nigeria's output connectedness with China, India and USA: a normalised generalised forecast error variance decomposition approach

This paper investigated the size of Nigeria's output connectedness with China, India and USA, with particular focus on Nigeria's latest democratic era that began in 1999. The study used the normalised generalised forecast error variance decomposition (GFEVD) of the underlying vector error correction (VEC) model to construct the connectedness measures. The findings reveal that India and China are the largest contributors of spillover index in the system. Overall, the size of the connectedness index of the economies is 34.55%, which shows remarkable output spillovers among these countries. The policy implication of these results is that Nigerian economic authorities should closely monitor the output fluctuations around the world, especially those of Nigeria's top trade partners like India and China in order to mitigate adverse output shocks.

Search for pair production of the heavy vectorlike top partner in same-sign dilepton signature at the HL-LHC

New vectorlike quarks are predicted in many new physics scenarios beyond the Standard Model (SM) and could potentially be discovered at the LHC. Based on a simplified model including a singlet vectorlike top partner with charge $2/3$, we investigate the process $pp\ensuremath{\rightarrow}TT$ via a $t$ channel induced by the couplings between the top partner with the first-generation SM quarks. We calculate the production cross section and further study the observability of the heavy top partner in the channel $T\ensuremath{\rightarrow}Wq$ at the high-luminosity LHC (HL-LHC) using final states with same-sign dileptons (electrons or muons), two jets, and missing transverse momentum. At the 14 TeV LHC with an integrated luminosity of $3000\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$, the $2\ensuremath{\sigma}$ exclusion limits, as well as the $5\ensuremath{\sigma}$ discovery reach in the parameter plane of the two variables ${g}^{*}\ensuremath{-}{R}_{L}$, are respectively obtained at the HL-LHC. We also obtain the $2\ensuremath{\sigma}$ exclusion limit on the coupling strength parameter ${g}^{*}$ in the case in which the vectorlike top partner is coupled only to the first-generation quarks.

Partial compositeness under precision scrutiny

We revisit the impact of top partial compositeness on electroweak precision observables in the misaligned vacuum basis. We identify a new source for S in the singlet mixing case, and for S-T in the bi-doublet mixing, stemming from misalignment in the gauge couplings of the top partners. Hence, a positive shift in T can be obtained in both cases, as preferred by the recent CDF measurement of the W mass. These results, obtained for the minimal fundamental coset SU(4)/Sp(4), apply to any composite Higgs model with top partial compositeness.

The other side of resistance: Challenges to inclusivity within civil society and the limits of international peace mediation

Research on resistance to the inclusion of civil society in peace mediation focuses on armed parties and elites as sites of resistance. Such focus grounds policies that prescribe various strategies and process designs that mediators could employ. The mediation of the Intergovernmental Authority on Development in South Sudan from 2012 to 2015 featured such strategies and attempts at various formats, including strong leverage from South Sudan’s neighbors and top development partners. However, civil society’s inclusion did not fully materialize, and armed clashes continued. Examining this mediation process, this article examines two structural challenges to civil society inclusion under-examined in mediation research. First, divisions within civil society can perpetuate divisions among warring parties and hinder the expected benefits of civil society inclusion. Second, the norms of consent and protecting lives considered definitional in peace mediation prioritize armed parties over civil society, limiting mediators’ ability to promote the latter’s inclusion and potentially encouraging further violence.

Pair production of the vectorlike top partner at future muon collider

Motivated by the recent interests in future high-energy muon colliders, we study the search potential of heavy singlet vectorlike top partner (VLQ-T) through the s-channel process μ+μ−→TT¯ at such facilities with s=6 TeV. We focus on the final signals via the T→Wb decay channel where one of the W bosons decays leptonically and the other decays hadronically. By carrying out a full simulation for the signals and the relevant Standard Model backgrounds, the 2σ exclusion limit and 5σ discovery prospects are, respectively, obtained on the VLQ-T mass and the branching ratio of T→Wb. The numerical results show that the future high-energy muon collider will be a promising hunting ground for such new particles.

Roadmap to explore vectorlike quarks decaying to a new scalar or pseudoscalar

The current experimental data allow for a sub-TeV colourless weak-singlet scalar or pseudoscalar. If such a singlet field is present together with TeV-range vectorlike top and bottom partners, there is a possibility that the heavy quarks decay dominantly to the singlet state and a third-generation quark, and the singlet state decays to quark and boson pairs. Such a possibility may arise in various models but it has not been explored experimentally, especially in the context of vectorlike-quark searches. We consider some minimal models, covering the possible weak representations of the top and bottom partners, that can be mapped to many well-motivated ultraviolet-complete theories. We chart out the possible interesting and unexplored signatures of the exotic decay of vectorlike quarks and identify benchmark points representing different signal topologies for the high luminosity LHC. We perform a general scan of the parameter space with the relevant direct search bounds and find that large regions, which do not require any fine-tuning, remain open for the unexplored channels. We also perform a simple projection study in the cleanest channel and indicate how other new but experimentally challenging channels can be used to probe more regions of the parameter space.

Phenomenological implications of the new Littlest Higgs model with T-parity

We investigate the parameter space of the new Littlest Higgs model with T-parity (NLHT) recently introduced to cure some pathologies of the original LHT. The model requires extra fermion content and additional pseudo-Goldstone bosons. While the heavy top quark sector is similar, there are both T-odd and T-even heavy quarks and leptons with masses proportional to just two sets of Yukawa matrices in flavor space, one more than in the LHT. The new scalars are a singlet and real triplet, T-odd, with masses controlled by gauge and Yukawa couplings, independent of the spontaneous symmetry breaking scale f, and hence potentially light. Imposing that no mass exceeds the cutoff scale, applying current lower bounds on vector-like quarks and assuming a simplified model with mass degenerate heavy fermions compatible with the heavy photon as dark matter constituent, we find that f gets constrained within the interval between 2 and 3 TeV, the common Yukawa coupling of heavy leptons gets fixed and the Yukawa coupling of heavy quarks becomes greatly correlated to the top quark Yukawa couplings. The particle spectrum is then bounded from below and above, with the (lightest) heavy photon at about 0.5 TeV, not far from the heavy leptons, the new scalars below 1 TeV, the usual complex scalar triplet close to the heavy weak bosons at about 1.5 to 2.5 TeV, and the heavy quarks and top quark partners between 2 and 5 TeV. The new scalars decay predominantly to a standard and a T-odd lepton and have a width comparable to that of the Higgs.

Discovery prospects of a vectorlike top partner decaying to a singlet boson

The possibility of a vectorlike top partner decaying to a new colourless weak-singlet scalar or pseudoscalar has attracted some attention in the literature. We investigate the production of a weak-singlet charge-$2/3$ $T$ quark that can decay to a spinless boson ($\Phi$) and a top quark at the LHC. Earlier, in 2203.13753, we have shown that in a large part of the parameter space, the $T\to t\Phi$ and the loop-induced $\Phi \to gg$ decays become the dominant decay modes for these particles. Here, we investigate the discovery prospects of the $T$ quark in this region through the above decays. In particular, we focus on the $pp\to TT\to (t\Phi)(t\Phi)\to (t(gg))\,(t(gg))$ channel. Separating this signal from the huge Standard Model background is a challenging task, forcing us to employ a multivariate machine-learning technique. We find that the above channel can be a discovery channel of the top partner in the large part of the parameter space where the above decay chain dominates. Our analysis is largely model-independent, and hence our results would be useful in a broad class of new physics models.

Charged dark matter in supersymmetric twin Higgs models

Supersymmetric Twin Higgs models ameliorate the fine-tuning of the electroweak scale originating from the heavy scalar top partners required by the non-discovery of them at the Large Hadron Collider. If the Lightest Supersymmetric Particle resides in the twin sector, it may play the role of dark matter even if it is charged under twin gauge interactions. We show that the twin stau is a viable candidate for charged dark matter, even if the twin electromagnetic gauge symmetry is unbroken, with thermal relic abundance that naturally matches the observed dark matter abundance. A wide parameter space satisfies all the experimental constraints including those on dark matter self-interactions. Twin stau dark matter can be observed in future direct detection experiments such as LUX-ZEPLIN. The stau has a mass in the range of 300–500 GeV, and in the minimal scenario, has a decay length long enough to be observed as a disappearing track or a long-lived particle at the Large Hadron Collider.