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Science ; 375(6576): eaaw9021, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34990240


Epithelial organoids are stem cell­derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.

Mucosa Intestinal/crescimento & desenvolvimento , Organogênese , Organoides/crescimento & desenvolvimento , Engenharia Tecidual , Animais , Diferenciação Celular , Forma Celular , Células Epiteliais/citologia , Hidrogéis , Mucosa Intestinal/anatomia & histologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Camundongos , Organoides/anatomia & histologia , Organoides/citologia , Organoides/metabolismo , Celulas de Paneth/citologia , Receptores Notch/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/fisiologia , Técnicas de Cultura de Tecidos , /metabolismo
Exp Mech ; 592019.
Artigo em Inglês | MEDLINE | ID: mdl-31579325
Exp Mech ; 592019.
Artigo em Inglês | MEDLINE | ID: mdl-31555000


A clear relationship between the population of brittle-fracture controlling flaws generated in a manufactured material and the distribution of strengths in a group of selected components is established. Assumptions regarding the strength-flaw size relationship, the volume of the components, and the number in the group, are clarified and the contracting effects of component volume and truncating effects of group number on component strength empirical distribution functions highlighted. A simple analytical example is used to demonstrate the forward prediction of population → distribution and the more important reverse procedure of empirical strength distribution → underlying flaw population. Three experimental examples are given of the application of the relationships to state-of-the-art micro- and nano-scale strength distributions to experimentally determine flaw populations: two on etched microelectromechanical systems (MEMS) structures and one on native and oxidized silicon nanowires. In all examples, the minimum threshold strength and conjugate maximum flaw size are very well estimated and the complete flaw population, including the minimum flaw size, are very poorly estimated, although etching, bimodal, and oxidation effects were clearly discernible. The results suggest that the best use of strength distribution information for MEMS manufacturers and designers might be in estimation of the strength threshold.

Exp Mech ; 60(2)2019.
Artigo em Inglês | MEDLINE | ID: mdl-33029033


The commercialization of additive manufacturing (AM) is underway in the aerospace and biomedical device industries [1, 2]. However, most metal parts produced by AM are limited to non-critical applications, since the various processes produce internal porosity, anisotropy, and microstructural heterogeneities [1, 3]. It has been implied that small-scale mechanical tests can advance measurement standards for AM applications by probing the effects of defects and heterogeneities on mechanical properties at more appropriate length scales [4, 5]. Traditionally, small-scale techniques have been used to characterize location- and orientation-specific mechanical properties in wrought materials [6-10]. A common method for excising mechanical test specimens from bulk parts with negligible influence on specimen integrity involves electrical discharge machining (EDM) [11]. This work demonstrates that excising meso-scale tensile specimens from additively manufactured parts enables tracking of sub-surface and visible features of interest (porosity and microstructural heterogeneities) throughout the entire gauge section such that the individual contributions to deformation behavior can be assessed.

Exp Mech ; 57(7): 1045-1055, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29056752


Atomic force microscopy (AFM) was used to assess the indentation modulus Ms and pull-off force Fpo in four case studies of distinct evidence types, namely hair, questioned documents, fingerprints, and explosive particle-surface interactions. In the hair study, Ms decreased and Fpo increased after adding conditioner and bleach to the hair. For the questioned documents, Ms and Fpo of two inks were markedly different; ballpoint pen ink exhibited smaller variations relative to the mean value than printer ink. The fingerprint case study revealed that both maximum height and Fpo decreased over a three-day period. Finally, the study on explosive particle-surface interactions illustrated that two fabrics exhibited similar Ms, but different Fpo. Overall, it was found that AFM addresses needs in forensic science as defined by several federal agencies, in particular an improved ability to expand the information extracted from evidence and to quantify its evidentiary value.