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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.

 

Severe geomagnetic storms can generate significant geo-electric fields that drive damaging quasi-direct currents within electric power grids. In "Space Weather Phase 1 Benchmarks," a report published in June 2018 by the Space Weather Operations, Research, and Mitigation (SWORM) Subcommittee on behalf of the National Science and Technology Council (NSTC), the "Induced Geo-electric Fields" working group (WG) summarized their objectives to: (1) assess the feasibility of establishing functional benchmarks for induced geo-electric fields using currently available storm data sets, existing models, and published literature; and (2) use the existing body of work to produce benchmarks for induced geo-electric fields for specific regions of the United States. To address this, they focused on developing a statistical product that captured maps of geo-electric hazard. Recently, our "next steps" WG reviewed these benchmarks to assess whether they are reasonable, aligned with the stated objectives, and up-to-date, based on new analyses as well as input from the community. We also considered whether the methodology used to derive them should be revised. In this presentation, we summarize the main findings of this WG, including recommendations for future data collection and/or studies that would improve their accuracy and usability, whilst at the same time, reducing the uncertainties associated with them. 

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 leptoquark pair production decaying into$$te^- \bar{t}e^+$$$t{e}^{-}\overline{t}{e}^{+}$or$$t\mu ^- \bar{t}\mu ^+$$$t{\mu }^{-}\overline{t}{\mu }^{+}$in final states with multiple leptons is presented. The search is based on a dataset ofppcollisions at$$\sqrt{s}=13~\text {TeV} $$$\sqrt{s}=13\text{TeV}$recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb$$^{-1}$$$_{}^{-1}$. Four signal regions, with the requirement of at least three light leptons (electron or muon) and at least two jets out of which at least one jet is identified as coming from ab-hadron, are considered based on the number of leptons of a given flavour. The main background processes are estimated using dedicated control regions in a simultaneous fit with the signal regions to data. No excess above the Standard Model background prediction is observed and 95% confidence level limits on the production cross section times branching ratio are derived as a function of the leptoquark mass. Under the assumption of exclusive decays into$$te^{-}$$$t{e}^{-}$($$t\mu ^{-}$$$t{\mu }^{-}$), the corresponding lower limit on the scalar mixed-generation leptoquark mass$$m_{\textrm{LQ}_{\textrm{mix}}^{\textrm{d}}}$$$m_{{\text{LQ}}_{\text{mix}}^{\text{d}}}$is at 1.58 (1.59) TeV and on the vector leptoquark mass$$m_{{\tilde{U}}_1}$$$m_{{\tilde{U}}_1}$at 1.67 (1.67) TeV in the minimal coupling scenario and at 1.95 (1.95) TeV in the Yang–Mills scenario.

 

A search for high-mass resonances decaying into a$\tau$-lepton and a neutrino using proton-proton collisions at a center-of-mass energy of$\sqrt{s}=13\mathrm{TeV}$is presented. The full run 2 data sample corresponding to an integrated luminosity of$139{\mathrm{fb}}^{-1}$recorded by the ATLAS experiment in the years 2015–2018 is analyzed. The$\tau$-lepton is reconstructed in its hadronic decay modes and the total transverse momentum carried out by neutrinos is inferred from the reconstructed missing transverse momentum. The search for new physics is performed on the transverse mass between the$\tau$-lepton and the missing transverse momentum. No excess of events above the Standard Model expectation is observed and upper exclusion limits are set on the$W^{\prime }\to \tau \nu$production cross section. Heavy$W^{\prime }$vector bosons with masses up to 5.0 TeV are excluded at 95% confidence level, assuming that they have the same couplings as the Standard Model$W$boson. For nonuniversal couplings,$W^{\prime }$bosons are excluded for masses less than 3.5–5.0 TeV, depending on the model parameters. In addition, model-independent limits on the visible cross section times branching ratio are determined as a function of the lower threshold on the transverse mass of the$\tau$-lepton and missing transverse momentum.