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Mammary morphogenesis is an orchestrated process involving differentiation, proliferation and organization of cells to form a bi-layered epithelial network of ducts and lobules embedded in stromal tissue. We have engineered a 3D biomimetic human breast that makes it possible to study how stem cell fate decisions translate to tissue-level structure and function. Using this advancement, we describe the mechanism by which breast epithelial cells build a complex three-dimensional, multi-lineage tissue by signaling through a collagen receptor. Discoidin domain receptor tyrosine kinase 1 induces stem cells to differentiate into basal cells, which in turn stimulate luminal progenitor cells via Notch signaling to differentiate and form lobules. These findings demonstrate how human breast tissue regeneration is triggered by transmission of signals from the extracellular matrix through an epithelial bilayer to coordinate structural changes that lead to formation of a complex ductal-lobular network.

Development of continuous biopharmaceutical manufacturing processes is an area of active research. This study considers the long‐term transgene copy number stability ofPichia pastorisin continuous bioreactors. We propose a model of copy number loss that quantifies population heterogeneity. An analytical solution is derived and compared with existing experimental data. The model is then used to provide guidance for stable operating timescales. The model is extended to consider copy number dependent growth such as in the case of Zeocin supplementation. The model is also extended to analyze a continuous seeding strategy. This study is a critical step towards understanding the impact of continuous processing on the stability ofPichia pastorisand the resultant products.

A search for pair production of squarks or gluinos decaying via sleptons or weak bosons is reported. The search targets a final state with exactly two leptons with same-sign electric charge or at least three leptons without any charge requirement. The analysed data set corresponds to an integrated luminosity of 139 fb⁻¹of proton-proton collisions collected at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Multiple signal regions are defined, targeting several SUSY simplified models yielding the desired final states. A single control region is used to constrain the normalisation of theWZ+ jets background. No significant excess of events over the Standard Model expectation is observed. The results are interpreted in the context of several supersymmetric models featuring R-parity conservation or R-parity violation, yielding exclusion limits surpassing those from previous searches. In models considering gluino (squark) pair production, gluino (squark) masses up to 2.2 (1.7) TeV are excluded at 95% confidence level.

A search for supersymmetry targeting the direct production of winos and higgsinos is conducted in final states with either two leptons (eorμ) with the same electric charge, or three leptons. The analysis uses 139 fb⁻¹ofppcollision data at$$ \sqrt{s} $$$\sqrt{s}$= 13 TeV collected with the ATLAS detector during Run 2 of the Large Hadron Collider. No significant excess over the Standard Model expectation is observed. Simplified and complete models with and withoutR-parity conservation are considered. In topologies with intermediate states including eitherWhorWZpairs, wino masses up to 525 GeV and 250 GeV are excluded, respectively, for a bino of vanishing mass. Higgsino masses smaller than 440 GeV are excluded in a naturalR-parity-violating model with bilinear terms. Upper limits on the production cross section of generic events beyond the Standard Model as low as 40 ab are obtained in signal regions optimised for these models and also for anR-parity-violating scenario with baryon-number-violating higgsino decays into top quarks and jets. The analysis significantly improves sensitivity to supersymmetric models and other processes beyond the Standard Model that may contribute to the considered final states.

A search for dark matter produced in association with a Higgs boson in final states with two hadronically decayingτ-leptons and missing transverse momentum is presented. The analysis uses 139 fb⁻¹of proton-proton collision data at$$ \sqrt{s} $$$\sqrt{s}$= 13 TeV collected by the ATLAS experiment at the Large Hadron Collider between 2015 and 2018. No evidence of physics beyond the Standard Model is found. The results are interpreted in terms of a 2HDM+amodel featuring two scalar Higgs doublets and a pseudoscalar singlet field. Exclusion limits on the parameters of the model in selected benchmark scenarios are derived at 95% confidence level. Model-independent limits are also set on the visible cross-section for processes beyond the Standard Model producing missing transverse momentum in association with a Higgs boson decaying intoτ-leptons.