Compliant rolling-contact architected materials for shape reconfigurability.

Architected materials can achieve impressive shape-changing capabilities according to how their microarchitecture is engineered. Here we introduce an approach for dramatically advancing such capabilities by utilizing wrapped flexure straps to guide the rolling motions of tightly packed micro-cams that constitute the material's microarchitecture. This approach enables high shape-morphing versatility and extreme ranges of deformation without accruing appreciable increases in strain energy or internal stress. Two-dimensional and three-dimensional macroscale prototypes are demonstrated, and the analytical theory necessary to design the proposed materials is provided and packaged as a software tool. An approach that combines two-photon stereolithography and scanning holographic optical tweezers is demonstrated to enable the fabrication of the proposed materials at their intended microscale

Additively manufacturable micro-mechanical logic gates.

Early examples of computers were almost exclusively based on mechanical devices. Although electronic computers became dominant in the past 60 years, recent advancements in three-dimensional micro-additive manufacturing technology provide new fabrication techniques for complex microstructures which have rekindled research interest in mechanical computations. Here we propose a new digital mechanical computation approach based on additively-manufacturable micro-mechanical logic gates. The proposed mechanical logic gates (i.e., NOT, AND, OR, NAND, and NOR gates) utilize multi-stable micro-flexures that buckle to perform Boolean computations based purely on mechanical forces and displacements with no electronic components. A key benefit of the proposed approach is that such systems can be additively fabricated as embedded parts of microarchitected metamaterials that are capable of interacting mechanically with their surrounding environment while processing and storing digital data internally without requiring electric power

Polytope Sector-Based Synthesis and Analysis of Microstructural Architectures With Tunable Thermal Conductivity and Expansion

The aim of this paper is to (1) introduce an approach, called polytope sector-based synthesis (PSS), for synthesizing 2D or 3D microstructural architectures that exhibit a desired bulk-property directionality (e.g., isotropic, cubic, orthotropic, etc.), and (2) provide general analytical methods that can be used to rapidly optimize the geometric parameters of these architectures such that they achieve a desired combination of bulk thermal conductivity and thermal expansion properties. Although the methods introduced can be applied to general beam-based microstructural architectures, we demonstrate their utility in the context of an architecture that can be tuned to achieve a large range of extreme thermal expansion coefficients—positive, zero, and negative. The material-property-combination region that can be achieved by this architecture is determined within an Ashby-material-property plot of thermal expansion versus thermal conductivity using the analytical methods introduced. These methods are verified using finite-element analysis (FEA) and both 2D and 3D versions of the design have been fabricated using projection microstereolithography.United States. Defense Advanced Research Projects Agency. Materials with Controlled Microstructural Architectures Progra

Rapid approach for cloning bacterial single-genes directly from soils

Obtaining functional genes of bacteria from environmental samples usually depends on library-based approach which is not favored as its large amount of work with small possibility of positive clones. A kind of bacterial single-gene encoding glutamine synthetase (GS) was selected as example to detect the efficiency of cloning strategy in this study. Five GS genes were directly cloned from soils using degenerate primers with two steps of nested polymerase chains reactions. The genes showed 94 to 99% amino acid identities to the homologs in the known database, and encoded proteins affiliated to GS I and GS II families, respectively. All the five genes could rescue the growth of Escherichia coli glutamine auxotroph mutant ET6017 in minimum medium (ammonium chloride was sole nitrogen source in this medium). This study develops one rapid approach for cloning bacterial single-genes directly from soils. Comparing with the conventional strategies for gene cloning from complex environmental samples, this method did not need making genomic library and isolating target genes from large amount of library clones. This approach distinctively demonstrates its advantages of rapidity and effectiveness particularly when it aims at cloning short single-genes that had known homologs in all kinds of nucleic acid databases.Keywords: Gene cloning, soil, glutamine synthetase, nested PCR, single-geneAfrican Journal of Biotechnology Vol. 12(32), pp. 5029-503

Mitochondrial Calcium Transporters Mediate Sensitivity to Noise-Induced Losses of Hair Cells and Cochlear Synapses

Mitochondria modulate cellular calcium homeostasis by the combined action of the mitochondrial calcium uniporter (MCU), a selective calcium entry channel, and the sodium calcium exchanger (NCLX), which extrudes calcium from mitochondria. In this study, we investigated MCU and NCLX in noise-induced hearing loss (NIHL) using adult CBA/J mice and noise-induced alterations of inner hair cell (IHC) synapses in MCU knockout mice. Following noise exposure, immunoreactivity of MCU increased in cochlear sensory hair cells of the basal turn, while immunoreactivity of NCLX decreased in a time- and exposure-dependent manner. Inhibition of MCU activity via MCU siRNA pretreatment or the specific pharmacological inhibitor Ru360 attenuated noise-induced loss of sensory hair cells and synaptic ribbons, wave I amplitudes, and NIHL in CBA/J mice. This protection was afforded, at least in part, through reduced cleavage of caspase 9 (CC9). Furthermore, MCU knockout mice on a hybrid genetic CD1 and C57/B6 background showed resistance to noise-induced seizures compared to wild-type littermates. Owing to the CD1 background, MCU knockouts and littermates suffer genetic high frequency hearing loss, but their IHCs remain intact. Noise-induced loss of IHC synaptic connections and reduction of auditory brainstem response (ABR) wave I amplitude were recovered in MCU knockout mice. These results suggest that cellular calcium influx during noise exposure leads to mitochondrial calcium overload via MCU and NCLX. Mitochondrial calcium overload, in turn, initiates cell death pathways and subsequent loss of hair cells and synaptic connections, resulting in NIHL

Reassessment of oxidative stress in idiopathic sudden hearing loss and preliminary exploration of the effect of physiological concentration of melatonin on prognosis

Background and purposeThe pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unclear, and there is no targeted treatment. This research aimed to verify the role of oxidative stress in ISSNHL and explore whether melatonin has a protective effect on hearing.Materials and methodsA total of 43 patients with ISSNHL and 15 healthy controls were recruited to detect the level of melatonin, reactive oxygen species (ROS), and total antioxidant capacity (TAC) in the blood and compared before and after treatment. Multivariate logistic regression models were performed to assess the factors relevant to the occurrence and improvement of ISSNHL.ResultsThe patients with ISSNHL showed significantly higher ROS levels than controls (4.42 ± 4.40 vs. 2.30 ± 0.59; p = 0.031). The levels of basal melatonin were higher (1400.83 ± 784.89 vs. 1095.97 ± 689.08; p = 0.046) and ROS levels were lower (3.05 ± 1.81 vs. 5.62 ± 5.56; p = 0.042) in the effective group as compared with the ineffective group. Logistic regression analysis showed that melatonin (OR = 0.999, 95% CI 0.997–1.000, p = 0.049), ROS (OR = 1.154, 95% CI 1.025–2.236, p = 0.037), and vertigo (OR = 3.011, 95% CI 1.339–26.983, p = 0.019) were independent factors associated with hearing improvement. Besides, the level of melatonin (OR = 0.999, 95% CI 0.998–1.000, p = 0.023) and ROS (OR = 3.248, 95% CI 1.109–9.516, p = 0.032) were associated with the occurrence of ISSNHL.ConclusionOur findings may suggest oxidative stress involvement in ISSNHL etiopathogenesis. The level of melatonin and ROS, and vertigo appear to be predictive of the effectiveness of hearing improvement following ISSNHL treatment

All-Trans Retinoic Acid Promotes TGF-β-Induced Tregs via Histone Modification but Not DNA Demethylation on Foxp3 Gene Locus

It has been documented all-trans retinoic acid (atRA) promotes the development of TGF-β-induced CD4(+)Foxp3(+) regulatory T cells (iTreg) that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs.Addition of atRA to naïve CD4(+)CD25(-) cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+) iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+) cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+) cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+) cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+) cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS) elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered.We have identified the cellular and molecular mechanism(s) by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation

Design and Optimization of Active Microarchitectured Metamaterials

A metamaterial is a material engineered to have a property that is not found in nature. Many different types of metamaterials have been widely researched across a variety of fields. The materials are usually constructed from a repeating pattern of unit cells, whose behavior is largely driven by the design of the mechanical structure and geometry configuration. In recent years, the advancements in micro-fabrication and micro-manipulation technologies, especially in micro-additive manufacturing technologies, provide new possibilities for the fabrication of metamaterial microstructure with embedded actuators and sensors. Unlike most existing microarchitectured metamaterials that exhibit their properties based solely on their microstructure’s topology and constituent material properties, active microarchitectured metamaterials exhibit the desired behavior through the incorporated actuators. In addition to producing the desired material properties accurately, active microarchitectured metamaterials are also capable of real-time tuning and arbitrary control of such properties, providing more flexibilities for the application of metamaterials.This research aims to provide general design guidelines for active microarchitectured metamaterials. The dissertation begins by reviewing the main methods for designing microstructure’s topologies based on compliant micro-mechanisms. This is followed by a discussion of the microstructure’s actuation design principles, including the optimal placement of actuators and the selection of micro-actuation physics. A numerical computational tool is then introduced that identifies the boundaries of the performance capabilities achieved by a specific design topology and generates the parameters that produce the optimal design instantiations. Examples of active microarchitectured metamaterial design are introduced and optimized to demonstrate such design principles

Optimizing the Geometry of Flexure System Topologies Using the Boundary Learning Optimization Tool

We introduce a new computational tool called the Boundary Learning Optimization Tool (BLOT) that identifies the boundaries of the performance capabilities achieved by general flexure system topologies if their geometric parameters are allowed to vary from their smallest allowable feature sizes to their largest geometrically compatible feature sizes for given constituent materials. The boundaries generated by the BLOT fully define the design spaces of flexure systems and allow designers to visually identify which geometric versions of their synthesized topologies best achieve desired combinations of performance capabilities. The BLOT was created as a complementary tool to the freedom and constraint topologies (FACT) synthesis approach in that the BLOT is intended to optimize the geometry of the flexure topologies synthesized using the FACT approach. The BLOT trains artificial neural networks to create models of parameterized flexure topologies using numerically generated performance solutions from different design instantiations of those topologies. These models are then used by an optimization algorithm to plot the desired topology’s performance boundary. The model-training and boundary-plotting processes iterate using additional numerically generated solutions from each updated boundary generated until the final boundary is guaranteed to be accurate within any average error set by the user. A FACT-synthesized flexure topology is optimized using the BLOT as a simple case study