Probing the luminal microenvironment of reconstituted epithelial microtissues.

Polymeric microparticles can serve as carriers or sensors to instruct or characterize tissue biology. However, incorporating microparticles into tissues for in vitro assays remains a challenge. We exploit three-dimensional cell-patterning technologies and directed epithelial self-organization to deliver microparticles to the lumen of reconstituted human intestinal microtissues. We also develop a novel pH-sensitive microsensor that can measure the luminal pH of reconstituted epithelial microtissues. These studies offer a novel approach for investigating luminal microenvironments and drug-delivery across epithelial barriers

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue–ECM boundary, rather than by differential homo- and heterotypic energies of cell–cell interaction. Surprisingly, interactions with the tissue–ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell–cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell–cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell–ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue–ECM boundary, rather than by differential homo- and heterotypic energies of cell–cell interaction. Surprisingly, interactions with the tissue–ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell–cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell–cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell–ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer

Annihilation of low energy antiprotons in silicon

The goal of the AE$\mathrm{\bar{g}}$IS experiment at the Antiproton Decelerator (AD) at CERN, is to measure directly the Earth's gravitational acceleration on antimatter. To achieve this goal, the AE$\mathrm{\bar{g}}$IS collaboration will produce a pulsed, cold (100 mK) antihydrogen beam with a velocity of a few 100 m/s and measure the magnitude of the vertical deflection of the beam from a straight path. The final position of the falling antihydrogen will be detected by a position sensitive detector. This detector will consist of an active silicon part, where the annihilations take place, followed by an emulsion part. Together, they allow to achieve 1$$ precision on the measurement of $\bar{g}$ with about 600 reconstructed and time tagged annihilations. We present here, to the best of our knowledge, the first direct measurement of antiproton annihilation in a segmented silicon sensor, the first step towards designing a position sensitive silicon detector for the AE$\mathrm{\bar{g}}$IS experiment. We also present a first comparison with Monte Carlo simulations (GEANT4) for antiproton energies below 5 MeVComment: 21 pages in total, 29 figures, 3 table

Opportunities for organoids as new models of aging.

The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research

Prospects for measuring the gravitational free-fall of antihydrogen with emulsion detectors

The main goal of the AEgIS experiment at CERN is to test the weak equivalence principle for antimatter. AEgIS will measure the free-fall of an antihydrogen beam traversing a moir\'e deflectometer. The goal is to determine the gravitational acceleration g for antihydrogen with an initial relative accuracy of 1% by using an emulsion detector combined with a silicon micro-strip detector to measure the time of flight. Nuclear emulsions can measure the annihilation vertex of antihydrogen atoms with a precision of about 1 - 2 microns r.m.s. We present here results for emulsion detectors operated in vacuum using low energy antiprotons from the CERN antiproton decelerator. We compare with Monte Carlo simulations, and discuss the impact on the AEgIS project.Comment: 20 pages, 16 figures, 3 table

Techniques for production and detection of 23S positronium

In this work, we show recent measurements of 23S long-lived positronium production via spontaneous decay from the 33P level. The possibility to tune the velocity of the 23S positronium, excited following this scheme, is presented. In the light of these results, we discuss the use of the 33P→23S transition to realize a monochromatic pulsed 23S positronium beam with low angular divergence. Preliminary tests of 23S beam production are presented. The possibility to overcome the natural 33P→23S branching ratio via stimulated emission, and thus increasing the intensity of the 23S source, is also shown. A position-sensitive detector for a pulsed beam of positronium, with spatial resolution of ≈ 90 μm, is finally described in view of its possible application for the spatial characterization of the 23S beam

Velocity-selected production of 2S3 metastable positronium

Positronium in the 2 3 S metastable state exhibits a low electrical polarizability and a long lifetime (1140 ns), making it a promising candidate for interferometry experiments with a neutral matter-antimatter system. In the present work, 2 3 S positronium is produced, in the absence of an electric field, via spontaneous radiative decay from the 3 3 P level populated with a 205-nm UV laser pulse. Thanks to the short temporal length of the pulse, 1.5 ns full width at half maximum, different velocity populations of a positronium cloud emitted from a nanochanneled positron-positronium converter were selected by delaying the excitation pulse with respect to the production instant. 2 3 S positronium atoms with velocity tuned between 7 7 10 4 ms 121 and 10 7 10 4 ms 121 were thus produced. Depending on the selected velocity, a 2 3 S production efficiency ranging from 3c0.8% to 3c1.7%, with respect to the total amount of emitted positronium, was obtained. The observed results give a branching ratio for the 3 3 P-2 3 S spontaneous decay of (9.7 \ub1 2.7)%. The present velocity selection technique could allow one to produce an almost monochromatic beam of 3c1 7 10 3 2 3 S atoms with a velocity spread of <10 4 ms 121 and an angular divergence of 3c50 mrad

A Moiré Deflectometer for Antimatter

The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics - the moirè deflectometer - for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter

Development of nuclear emulsions operating in vacuum for the AEgIS experiment

For the first time the AEgIS (Antihydrogen Experiment: Gravity, Interferometry, Spectroscopy) experiment will measure the Earth\u2019s local gravitational acceleration g on antimatter through the evaluation of the vertical displacement of an antihydrogen horizontal beam. This will be a model independent test of the Weak Equivalence Principle at the base of the general relativity. The initial goal of a g measurement with a relative uncertainty of 1% will be achieved with less than 1000 detected antihydrogens, provided that their vertical position could be determined with a precision of a few micrometers. An emulsion based detector is very suitable for this purpose featuring an intrinsic sub-micrometric spatial resolution. Nevertheless, the AEgIS experiment re- quires unprecedented operational conditions for this type of detector, namely vacuum environment and very low temperature. An intense R&D activity is presently going on to optimize the detector for the AEgIS experimental requirements with rather encouraging results