Epigenomic Exploration of the Human Brain

2018 ◽  
pp. 144-164
Author(s):  
Tobias B. Halene ◽  
Gregor Hasler ◽  
Amanda Mitchell ◽  
Schahram Akbarian

The exploration of the epigenome has become a flourishing area in the neurosciences. Scientists increasingly appreciate that even the position of genetic material within the nucleus is purposeful, and its spatial orientation conveys information with critical influence on transcription, genome integrity, and stability. Together, epigenetic and three-dimensional genome data hold promise to reveal how DNA variants and mutations come into play in brain disease. Powerful new technologies can now map transcriptome, DNA-methylome, and other epigenetic regulators on the level of single brain cells. Many of these findings are limited to preclinical studies. Nevertheless, the advent of chromatin-modifying drugs in cancer therapy and the discovery that approved medications such as valproic acid and lithium have a chromatin-modifying effect have spurred hopes for improved biological therapies. Here we summarize current concepts and emerging insights into epigenetic regulation, with a focus on human brain and the neurobiology and pharmacology of psychiatric disorders.

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2239
Author(s):  
Nicholas Rodriguez ◽  
Samantha Ruelas ◽  
Jean-Baptiste Forien ◽  
Nikola Dudukovic ◽  
Josh DeOtte ◽  
...  

Recent advances in additive manufacturing, specifically direct ink writing (DIW) and ink-jetting, have enabled the production of elastomeric silicone parts with deterministic control over the structure, shape, and mechanical properties. These new technologies offer rapid prototyping advantages and find applications in various fields, including biomedical devices, prosthetics, metamaterials, and soft robotics. Stereolithography (SLA) is a complementary approach with the ability to print with finer features and potentially higher throughput. However, all high-performance silicone elastomers are composites of polysiloxane networks reinforced with particulate filler, and consequently, silicone resins tend to have high viscosities (gel- or paste-like), which complicates or completely inhibits the layer-by-layer recoating process central to most SLA technologies. Herein, the design and build of a digital light projection SLA printer suitable for handling high-viscosity resins is demonstrated. Further, a series of UV-curable silicone resins with thiol-ene crosslinking and reinforced by a combination of fumed silica and MQ resins are also described. The resulting silicone elastomers are shown to have tunable mechanical properties, with 100–350% elongation and ultimate tensile strength from 1 to 2.5 MPa. Three-dimensional printed features of 0.4 mm were achieved, and complexity is demonstrated by octet-truss lattices that display negative stiffness.


Author(s):  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Ilia V. Soloviev ◽  
Alexei M. Ratnikov ◽  
Ivan Y. Iourov

Author(s):  
W. N. P. Hung ◽  
M. M. Agnihotri ◽  
M. Y. Ali ◽  
S. Yuan

Traditional micromanufacturing has been developed for semiconductor industry. Selected micro electrical mechanical systems (MEMS) have been successfully developed and implemented in industry. Since current MEMS are designed for manufacture using microelectronics processes, they are limited to two-dimensional profiles and semiconductor based materials. Such shape and material constraints would exclude many applications that require biocompatibility, dynamic stress, and high ductility. New technologies are sought to fabricate three dimensional microcomponents using robust materials for demanding applications. To be cost effective, such microdevices must be economically mass producible. Molding is one of the promising replication techniques to mass produce components from polymers and polymer-based composites. This paper presents the development of a micromolding process to produce thermoplastic microcomponents. Mold design required precision fitting and was integrated with a vacuum pump to minimize air trap in mold cavities. Nickel and aluminum mold inserts were used for the study; their cavities were fabricated by combinations of available micromachining processes like laser micromachining, micromilling, micro electrical discharge machining, and focused ion beam sputtering. High and low density polyethylene, polystyrene polymers were used for this study. The effects of polymer molecular structures, molding temperature, time, and pressure on molding results were studied. Simulation of stress in the microcomponents, plastic flow in microchannels, and mold defects was performed and compare with experimental data. The research results showed that a microcomponent can be fabricated to the minimum size of 10 ± 1μm (0.0004 inch) with surface roughness <10 nm Rt. Molding of micro-size geartrains and orthopedic meso-size fasteners was completed to illustrate the capability of this process.


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