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.
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Abstract Development of continuous biopharmaceutical manufacturing processes is an area of active research. This study considers the long‐term transgene copy number stability of
Pichia pastoris in 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 pastoris and the resultant products. -
Free, publicly-accessible full text available August 1, 2024
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Free, publicly-accessible full text available July 1, 2024
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Abstract A study of the charge conjugation and parity ( $$\textit{CP}$$ CP ) properties of the interaction between the Higgs boson and $$\tau $$ τ -leptons is presented. The study is based on a measurement of $$\textit{CP}$$ CP -sensitive angular observables defined by the visible decay products of $$\tau $$ τ -leptons produced in Higgs boson decays. The analysis uses 139 fb $$^{-1}$$ - 1 of proton–proton collision data recorded at a centre-of-mass energy of $$\sqrt{s}= 13$$ s = 13 TeV with the ATLAS detector at the Large Hadron Collider. Contributions from $$\textit{CP}$$ CP -violating interactions between the Higgs boson and $$\tau $$ τ -leptons are described by a single mixing angle parameter $$\phi _{\tau }$$ ϕ τ in the generalised Yukawa interaction. Without constraining the $$H\rightarrow \tau \tau $$ H → τ τ signal strength to its expected value under the Standard Model hypothesis, the mixing angle $$\phi _{\tau }$$ ϕ τ is measured to be $$9^{\circ } \pm 16^{\circ }$$ 9 ∘ ± 16 ∘ , with an expected value of $$0^{\circ } \pm 28^{\circ }$$ 0 ∘ ± 28 ∘ at the 68% confidence level. The pure $$\textit{CP}$$ CP -odd hypothesis is disfavoured at a level of 3.4 standard deviations. The results are compatible with the predictions for the Higgs boson in the Standard Model.more » « lessFree, publicly-accessible full text available July 1, 2024
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A bstract A search for Higgs boson pair production in events with two b -jets and two τ -leptons is presented, using a proton–proton collision dataset with an integrated luminosity of 139 fb − 1 collected at $$ \sqrt{s} $$ s = 13 TeV by the ATLAS experiment at the LHC. Higgs boson pairs produced non-resonantly or in the decay of a narrow scalar resonance in the mass range from 251 to 1600 GeV are targeted. Events in which at least one τ -lepton decays hadronically are considered, and multivariate discriminants are used to reject the backgrounds. No significant excess of events above the expected background is observed in the non-resonant search. The largest excess in the resonant search is observed at a resonance mass of 1 TeV, with a local (global) significance of 3 . 1 σ (2 . 0 σ ). Observed (expected) 95% confidence-level upper limits are set on the non-resonant Higgs boson pair-production cross-section at 4.7 (3.9) times the Standard Model prediction, assuming Standard Model kinematics, and on the resonant Higgs boson pair-production cross-section at between 21 and 900 fb (12 and 840 fb), depending on the mass of the narrow scalar resonance.more » « lessFree, publicly-accessible full text available July 1, 2024
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A bstract A search for heavy Higgs bosons produced in association with a vector boson and decaying into a pair of vector bosons is performed in final states with two leptons (electrons or muons) of the same electric charge, missing transverse momentum and jets. A data sample of proton–proton collisions at a centre-of-mass energy of 13 TeV recorded with the ATLAS detector at the Large Hadron Collider between 2015 and 2018 is used. The data correspond to a total integrated luminosity of 139 fb − 1 . The observed data are in agreement with Standard Model background expectations. The results are interpreted using higher-dimensional operators in an effective field theory. Upper limits on the production cross-section are calculated at 95% confidence level as a function of the heavy Higgs boson’s mass and coupling strengths to vector bosons. Limits are set in the Higgs boson mass range from 300 to 1500 GeV, and depend on the assumed couplings. The highest excluded mass for a heavy Higgs boson with the coupling combinations explored is 900 GeV. Limits on coupling strengths are also provided.more » « lessFree, publicly-accessible full text available July 1, 2024