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1.
Stem Cell Reports ; 15(5): 1037-1046, 2020 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-33125876

RESUMEN

Epigenetic regulation by the SWI/SNF complex is essential for normal self-renewal capacity and pluripotency of human pluripotent stem cells (hPSCs). It has been shown that different subunits of the complex have a distinct role in this regulation. Specifically, the SMARCB1 subunit has been shown to regulate the activity of enhancers in diverse types of cells, including hPSCs. Here, we report the establishment of conditional hPSC lines, enabling control of SMARCB1 expression from complete loss of function to significant overexpression. Using this system, we show that any deviation from normal SMARCB1 expression leads to cell differentiation. We further found that SMARCB1 expression is not required for differentiation of hPSCs into progenitor cells, but rather for later stages of differentiation. Finally, we identify SMARCB1 as a critical player in regulation of cell-cell and cell-ECM interactions in hPSCs and show that this regulation is mediated at least in part by the WNT pathway.


Asunto(s)
Diferenciación Celular , Células Madre Embrionarias Humanas/citología , Células Madre Pluripotentes Inducidas/citología , Proteína SMARCB1/metabolismo , Comunicación Celular , Línea Celular , Epigénesis Genética , Matriz Extracelular/metabolismo , Regulación de la Expresión Génica , Humanos , Proteína SMARCB1/genética , Células Madre/metabolismo , Vía de Señalización Wnt
2.
Proc Natl Acad Sci U S A ; 115(46): E10830-E10838, 2018 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-30373819

RESUMEN

Traditional fabrication techniques for microfluidic devices utilize a planar chip format that possesses limited control over the geometry of and materials placement around microchannel cross-sections. This imposes restrictions on the design of flow fields and external forces (electric, magnetic, piezoelectric, etc.) that can be imposed onto fluids and particles. Here we report a method of fabricating microfluidic channels with complex cross-sections. A scaled-up version of a microchannel is dimensionally reduced through a thermal drawing process, enabling the fabrication of meters-long microfluidic fibers with nonrectangular cross-sectional shapes, such as crosses, five-pointed stars, and crescents. In addition, by codrawing compatible materials, conductive domains can be integrated at arbitrary locations along channel walls. We validate this technology by studying unexplored regimes in hydrodynamic flow and by designing a high-throughput cell separation device. By enabling these degrees of freedom in microfluidic device design, fiber microfluidics provides a method to create microchannel designs that are inaccessible using planar techniques.


Asunto(s)
Técnicas Analíticas Microfluídicas/métodos , Microfluídica/instrumentación , Microfluídica/métodos , Separación Celular , Diseño de Equipo/métodos , Hidrodinámica , Dispositivos Laboratorio en un Chip
3.
Nat Commun ; 8(1): 1435, 2017 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-29127280

RESUMEN

Microelectromechanical systems (MEMS) enable many modern-day technologies, including actuators, motion sensors, drug delivery systems, projection displays, etc. Currently, MEMS fabrication techniques are primarily based on silicon micromachining processes, resulting in rigid and low aspect ratio structures. In this study, we report on the discovery of MEMS functionality in fibres, thereby opening a path towards flexible, high-aspect ratio, and textile MEMS. The method used for generating these MEMS fibres leverages a preform-to-fibre thermal drawing process, in which the MEMS architecture and materials are embedded into a preform and drawn into kilometers of microstructured multimaterial fibre devices. The fibre MEMS functionality is enabled by an electrostrictive P(VDF-TrFE-CFE) ferrorelaxor terpolymer layer running the entire length of the fibre. Several modes of operation are investigated, including thickness-mode actuation with over 8% strain at 25 MV m-1, bending-mode actuation due to asymmetric positioning of the electrostrictive layer, and resonant fibre vibration modes tunable under AC-driving conditions.

4.
Nat Commun ; 8(1): 364, 2017 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-28848237

RESUMEN

The control of mass transport using porous fibers is ubiquitous, with applications ranging from filtration to catalysis. Yet, to date, porous fibers have been made of single materials in simple geometries, with limited function. Here we report the fabrication and characterization of thermally drawn multimaterial fibers encompassing internal porous domains alongside non-porous insulating and conductive materials, in highly controlled device geometries. Our approach utilizes phase separation of a polymer solution during the preform-to-fiber drawing process, generating porosity as the fiber is drawn. Engineering the preform structure grants control over the geometry and materials architecture of the final porous fibers. Electrical conductivity of the selectrolyte-filled porous domains is substantiated through ionic conductivity measurements using electrodes thermally drawn in the cross-section. Pore size tunability between 500 nm-10 µm is established by regulating the phase separation kinetics. We further demonstrate capillary breakup of cylindrical porous structures porous microspheres within the fiber core.Porous polymer fibers show great potential for a range of applications, but their simple structures typically limit their functionality. Here, the authors combine a thermal drawing process with polymer solution phase separation to fabricate porous multimaterial fibers with complex internal architectures.

5.
Proc Natl Acad Sci U S A ; 114(28): 7240-7245, 2017 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-28642348

RESUMEN

Crystallization of microdroplets of molten alloys could, in principle, present a number of possible morphological outcomes, depending on the symmetry of the propagating solidification front and its velocity, such as axial or spherically symmetric species segregation. However, because of thermal or constitutional supercooling, resulting droplets often only display dendritic morphologies. Here we report on the crystallization of alloyed droplets of controlled micrometer dimensions comprising silicon and germanium, leading to a number of surprising outcomes. We first produce an array of silicon-germanium particles embedded in silica, through capillary breakup of an alloy-core silica-cladding fiber. Heating and subsequent controlled cooling of individual particles with a two-wavelength laser setup allows us to realize two different morphologies, the first being a silicon-germanium compositionally segregated Janus particle oriented with respect to the illumination axis and the second being a sphere made of dendrites of germanium in silicon. Gigapascal-level compressive stresses are measured within pure silicon solidified in silica as a direct consequence of volume-constrained solidification of a material undergoing anomalous expansion. The ability to generate microspheres with controlled morphology and unusual stresses could pave the way toward advanced integrated in-fiber electronic or optoelectronic devices.

6.
Adv Mater ; 29(1)2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27797161

RESUMEN

Thermally drawn metal-insulator-semiconductor fibers provide a scalable path to functional fibers. Here, a ladder-like metal-semiconductor-metal photodetecting device is formed inside a single silica fiber in a controllable and scalable manner, achieving a high density of optoelectronic components over the entire fiber length and operating at a bandwidth of 470 kHz, orders of magnitude larger than any other drawn fiber device.

7.
Nat Commun ; 7: 12807, 2016 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-27698454

RESUMEN

Fibres with electronic and photonic properties are essential building blocks for functional fabrics with system level attributes. The scalability of thermal fibre drawing approach offers access to large device quantities, while constraining the devices to be translational symmetric. Lifting this symmetry to create discrete devices in fibres will increase their utility. Here, we draw, from a macroscopic preform, fibres that have three parallel internal non-contacting continuous domains; a semiconducting glass between two conductors. We then heat the fibre and generate a capillary fluid instability, resulting in the selective transformation of the cylindrical semiconducting domain into discrete spheres while keeping the conductive domains unchanged. The cylindrical-to-spherical expansion bridges the continuous conducting domains to create ∼104 self-assembled, electrically contacted and entirely packaged discrete spherical devices per metre of fibre. The photodetection and Mie resonance dependent response are measured by illuminating the fibre while connecting its ends to an electrical readout.

8.
Phys Rev E Stat Nonlin Soft Matter Phys ; 86(6 Pt 2): 066209, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23368026

RESUMEN

We study theoretically the generation of a continuous-wave signal by two weakly coupled delay-line oscillators. In such oscillators, the cavity length is longer than the wavelength of the signal. We show by using an analytical solution and comprehensive numerical simulations that in delay-line oscillators, the dynamics of the amplitude response cannot be neglected even when the coupling between the oscillators is weak. Therefore, weakly coupled delay-line oscillators cannot be accurately modeled by using coupled phase-oscillator models. In particular, we show that synchronization between the oscillators can be obtained in cases that are not allowed by coupled phase-oscillator models. We study the stability of the continuous-wave solutions. In delay-line oscillators, several cavity modes can potentially oscillate. To ensure stability, the bandwidth of the delay-line oscillator should be limited. We show that the weakly coupled delay-line oscillator model that is described in this paper can be used to accurately model the synchronization between two weakly coupled optoelectronic oscillators. A very good quantitative agreement is obtained between a comprehensive numerical model to study optoelectronic oscillators and the model results given in this paper.

9.
Opt Express ; 19(18): 17599-608, 2011 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-21935127

RESUMEN

We demonstrate experimentally passive mode-locking of an optoelectronic oscillator which generates a single-cycle radio-frequency pulse train. The measured pulse to pulse jitter was less than 5 ppm of the round-trip duration. The pulse waveform was repeated each round-trip. This result indicates that the relative phase between the pulse envelope and the carrier wave is autonomously locked. The results demonstrate, for the first time, that single-cycle pulses can be directly generated by a passive mode-locked oscillator. The passive mode-locked optoelectronic oscillator is important for developing novel radars and radio-frequency pulsed sources and it enables studying directly the physics of single-cycle pulse generation.

10.
Opt Express ; 18(20): 21461-76, 2010 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-20941042

RESUMEN

We describe a comprehensive computational model for singleloop and dual-loop optoelectronic oscillators (OEOs). The model takes into account the dynamical effects and noise sources that are required to accurately model OEOs. By comparing the computational and experimental results in a single-loop OEO, we determined the amplitudes of the white noise and flicker noise sources. We found that the flicker noise source contains a strong component that linearly depends on the loop length. Therefore, the flicker noise limits the performance of long-cavity OEOs (≧5 km) at low frequencies (f<500 Hz). The model for a single-loop OEO was extended to model the dual-loop injection-locked OEO (DIL-OEO). The model gives the phase-noise, the spur level, and the locking range of each of the coupled loops in the OEO. An excellent agreement between theory and experiment is obtained for the DIL-OEO. Due to its generality and accuracy, the model is important for both designing OEOs and studying the physical effects that limit their performance. We demonstrate theoretically that it is possible to reduce the first spur in the DIL-OEO by more than 20 dB relative to its original performance by changing its parameters. This theoretical result has been experimentally verified.

11.
Opt Lett ; 33(24): 2883-5, 2008 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-19079480

RESUMEN

We analyze the distribution of the rf spectrum in optoelectronic oscillators due to the finite duration of the spectrum measurement. The distribution of the periodogram or the rf spectrum at a given frequency is calculated using a reduced model and is compared to a comprehensive numerical simulation. The model shows that the rf spectrum at a given frequency fluctuates from measurement to measurement with an exponential distribution.

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