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Articular cartilage is comprised of two main components, the extracellular matrix (ECM) and the pericellular matrix (PCM). The PCM helps to protect chondrocytes in the cartilage from mechanical loads, but in patients with osteoarthritis, the PCM is weakened, resulting in increased chondrocyte stress. As chondrocytes are responsible for matrix synthesis and maintenance, it is important to understand how mechanical loads affect the cellular responses of chondrocytes. Many studies have examined chondrocyte responses to in vitro mechanical loading by embedding chondrocytes in 3-D hydrogels. However, these experiments are mostly performed in the absence of PCM, which may obscure important responses to mechanotransduction. Here, drop-based microfluidics is used to culture single chondrocytes in alginate microgels for cell-directed PCM synthesis that closely mimics the in vivo microenvironment. Chondrocytes formed PCM over 10 days in these single-cell 3-D microenvironments. Mechanotransduction studies were performed, in which single-cell microgels mimicking the cartilage PCM were embedded in high-stiffness agarose. After physiological dynamic compression in a custom-built bioreactor, microgels exhibited distinct metabolomic profiles from both uncompressed and monolayer controls. These results demonstrate the potential of single cell encapsulation in alginate microgels to advance cartilage tissue engineering and basic chondrocyte mechanobiology.

A bstract A search is presented for a heavy W′ boson resonance decaying to a B or T vector-like quark and a t or a b quark, respectively. The analysis is performed using proton-proton collisions collected with the CMS detector at the LHC. The data correspond to an integrated luminosity of 138 fb − 1 at a center-of-mass energy of 13 TeV. Both decay channels result in a signature with a t quark, a Higgs or Z boson, and a b quark, each produced with a significant Lorentz boost. The all-hadronic decays of the Higgs or Z boson and of the t quark are selected using jet substructure techniques to reduce standard model backgrounds, resulting in a distinct three-jet W′ boson decay signature. No significant deviation in data with respect to the standard model background prediction is observed. Upper limits are set at 95% confidence level on the product of the W′ boson cross section and the final state branching fraction. A W′ boson with a mass below 3.1 TeV is excluded, given the benchmark model assumption of democratic branching fractions. In addition, limits are set based on generalizations of these assumptions. These are the most sensitive limits to datemore »for this final state.« less

Abstract A new algorithm is presented to discriminate reconstructed hadronic decays of tau leptons ( τ h ) that originate from genuine tau leptons in the CMS detector against τ h candidates that originate from quark or gluon jets, electrons, or muons. The algorithm inputs information from all reconstructed particles in the vicinity of a τ h candidate and employs a deep neural network with convolutional layers to efficiently process the inputs. This algorithm leads to a significantly improved performance compared with the previously used one. For example, the efficiency for a genuine τ h to pass the discriminator against jets increases by 10–30% for a given efficiency for quark and gluon jets. Furthermore, a more efficient τ h reconstruction is introduced that incorporates additional hadronic decay modes. The superior performance of the new algorithm to discriminate against jets, electrons, and muons and the improved τ h reconstruction method are validated with LHC proton-proton collision data at √ s = 13 TeV.