Convergence of Gradient Descent for Low-Rank Matrix Approximation

This paper provides a proof of global convergence of gradient search for low-rank matrix approximation. Such approximations have recently been of interest for large-scale problems, as well as for dictionary learning for sparse signal representations and matrix completion. The proof is based on the interpretation of the problem as an optimization on the Grassmann manifold and Fubiny-Study distance on this space

Titin-dependent biomechanical feedback tailors sarcomeres to specialized muscle functions in insects

Sarcomeres are the universal contractile units of muscles that enable animals to move. Insect muscles display a remarkable functional diversity: they operate at extremely different contraction frequencies (ranging from ~1 to 1000 hertz) and amplitudes during flying, walking, and crawling. This is puzzling because sarcomeres are built from essentially the same actin-myosin components. Here, we address how functionally different sarcomeres are made. We show that the giant protein titin and the regulation of developmental contractility are key for the sarcomere specializations. I-band titin spans and determines the length of the sarcomeric I-band in a muscle type–specific manner. Unexpectedly, I-band titin also rules the length of the force-generating myosin filament using a feedback mechanism that is modulated by myosin contractility. We propose a model of how sarcomere specializations in insects are tuned, provide evidence for this model, and discuss its validity beyond insects

A microfluidic platform integrating functional vascularized organoids-on-chip

The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics

Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation.We acknowledge funding from an EPSRC Platform grant which supported McMurray and a Wellcome Trust project grant which supported Wann and McMurray. Wann is now supported on an ARUK project grant. Thompson was funded by a BBSRC PhD studentshi

Détermination des épaisseurs de films très minces de SiO2\mathsf{_2} sur silicium par microscopie électronique en transmission, ellipsométrie spectroscopique et spectroscopie de photoélectrons

High Resolution cross-sectional Transmission Electron Microscopy (HRTEM), Spectroscopic ellipsometry and X-ray photoelectron spectroscopy (XPS) have been used conjointly to measure accurately the thickness of very thin SiO$_2$ films (20-200 Å) of electronic quality. HRTEM has been used to calibrate both ellipsometry and XPS technics. A procedure to measure the absolute oxide film thicknesses has been defined for each of the three methods.La Microscopie Electronique en Transmission à Haute Résolution (METHR), l'ellipsométrie spectroscopique et la spectroscopie de photoélectrons XPS ont été utilisées conjointement pour évaluer avec précision l'épaisseur de couches très minces de SiO$_2$ (20-200 Å) de qualité électronique. Une calibration de l'ellipsométrie et de l'XPS par la METHR a été effectuée. Une procédure de mesure de l'épaisseur absolue d'oxydes fins a été déterminée pour les trois méthodes

Effects of Heating Samples on the Extended Defect Generation During Pulsed Electron Beam Annealing of Silicon

ABSTRACTA non destructive SEM observation method has been applied to investigate the extended defects created by pulsed electron beam annealing of arsenic–implanted silicon. The defect study was performed on bevelled samples after irradiation using variable beam fluences for both a 20°C or a 450°C specimen starting temperature. Dislocation generation resulting in subgrain boundaries formation occurs during regrowth of the silicon layer which has been heated up to the melt point or higher. For the rather penetrating electron beam pulse used in this work the subgrain size and their depth extent depend on the beam fluence and the substrate temperature. For 450°C pre‐heated samples, annealing of the arsenic implant is possible without any stable extended defect creation using the 1.0 – 1.2 J.cm−2 fluence range.</jats:p

Characterization of the epidermal-dermal junction in hiPSC-derived skin organoids

Human induced pluripotent stem cell (hiPSC)-derived hair-bearing skin organoids offer exciting new possibilities for modeling diseases like epidermolysis bullosa (EB). These inherited diseases affect 1 in 30,000 people worldwide and result from perturbed expression and/or structure of components of the epidermal-dermal junction (EDJ). To establish whether hiPSC-derived skin organoids might be able to capture salient features of EB, it is thus important to characterize their EDJ. Here, we report successful generation of hair-bearing skin organoids from two hiPSC lines that exhibited fully stratified interfollicular epidermis. Using immunofluorescence and electron microscopy, we showed that basal keratinocytes in organoids adhere to laminin-332 and type IV collagen-rich basement membrane via type I hemidesmosomes and integrin 81-based adhesion complexes. Importantly, we demonstrated that EDJs in organoids are almost devoid of type VII collagen, a fibril that mediates anchorage of the epidermis to dermis. This should be considered when using skin organoids for EB modeling.Stem cells & developmental biolog