Search

As the physical size of a communication system for satellites or unmanned aerial vehicles demands to be reduced, a compact antenna with high directivity is proposed as a core element essential to the wireless device. Instead of using a horn or an array antenna, a unit planar antenna is combined with a surface-modulated lens to convert a low antenna gain to a high antenna gain. The lens is not a metal-patterned PCB but is dielectric, which is neither curved nor very wide. This palm-sized lens comprises pixels with different heights from the backside of PolyPhenylene Sulfide (PPS) as the dielectric base. The antenna gain from the unit antenna of 4.5 cm × 4.5 cm is enhanced by 10 dB with the help of a compact dielectric lens of 7.5 cm × 7.5 cm at 24.5 GHz as the frequency of interest. The antenna design is verified by far-field measurement as well as near-field observation, including sensing a metal object behind a blocking wall by using an RF test bench. Moreover, antenna performance is understood by making a comparison with conventional designs of antennas in terms of directivity and physical sizes. [ABSTRACT FROM AUTHOR]

This study reported an efficient and operationally simple desulfonylation method. A one‐pot protoboration‐desulfonylation of alkenyl sulfones with various sulfone heads under copper catalysis using diboron, and an alkoxide base in DMF afforded high yields of the corresponding alkenes. This reaction operates well in the presence of water and air for unsaturated sulfones with an aryl or alkyl substituent and for widely used phenyl and other sulfonyl families. Use of ligand is not necessary and byproducts from the reaction are relatively benign. [ABSTRACT FROM AUTHOR]

Disruption of mitochondrial function and protein homeostasis plays a central role in aging. However, how these processes interact and what governs their failure in aging remain poorly understood. Here, we showed that ceramide biosynthesis controls the decline in mitochondrial and protein homeostasis during muscle aging. Analysis of transcriptome datasets derived from muscle biopsies obtained from both aged individuals and patients with a diverse range of muscle disorders revealed that changes in ceramide biosynthesis, as well as disturbances in mitochondrial and protein homeostasis pathways, are prevalent features in these conditions. By performing targeted lipidomics analyses, we found that ceramides accumulated in skeletal muscle with increasing age across Caenorhabditis elegans, mice, and humans. Inhibition of serine palmitoyltransferase (SPT), the rate-limiting enzyme of the ceramide de novo synthesis, by gene silencing or by treatment with myriocin restored proteostasis and mitochondrial function in human myoblasts, in C. elegans, and in the skeletal muscles of mice during aging. Restoration of these age-related processes improved health and life span in the nematode and muscle health and fitness in mice. Collectively, our data implicate pharmacological and genetic suppression of ceramide biosynthesis as potential therapeutic approaches to delay muscle aging and to manage related proteinopathies via mitochondrial and proteostasis remodeling. Suppressing ceramides to stall muscle aging: Aging is associated with disrupted mitochondrial function and proteostasis, but the mechanisms controlling these processes are not fully understood. Here, Lima and colleagues identified that changes in ceramide biosynthesis are a feature of human muscle aging and disease. Inhibition of serine palmitoyltransferase (SPT), a critical enzyme in ceramide biosynthesis, through gene silencing or pharmacological treatment resulted in improved proteostasis and mitochondrial function in human myotubes as well as Caenorhabditis elegans and mice during aging. This improved the health and lifespan of C. elegans as well as muscle function and fitness in mice. These findings suggest that suppression of ceramide biosynthesis may be an approach to treat disorders associated with muscle aging in humans. —MN [ABSTRACT FROM AUTHOR]

A practical configuration for generating narrowband terahertz (THz) pulses based on plasma dipole oscillations (PDOs) is studied using two-dimensional particle-in-cell simulations. In this scheme, two slightly detuned laser pulses collide obliquely in a helium gas. Plasma strips are generated along the paths of the laser pulses by field ionization. The PDO created in the overlap region of the two laser pulses emits a THz pulse with a peak electric field strength of a few gigavolt per meter. An energy conversion efficiency of 0.542 × 10 − 3 is achieved for laser pulse intensities 4.82 × 10 16 W / c m 2 , a spot radii of 5 μ m , and a collision angle of 10.8 °. A force balance model is extended for the obliquely colliding configuration of the pulses. As the complications, such as generating plasmas separately or aligning the beams with preformed plasma, are eliminated from our new configuration, this makes a future experimental study of PDO more straightforward. [ABSTRACT FROM AUTHOR]

We guide the use of organ-on-chip technology in tissue engineering applications. Organ-on-chip technology is a form of microengineered cell culture platform that elaborates the in-vivo like organ or tissue microenvironments. The organ-on-chip platform consists of microfluidic channels, cell culture chambers, and stimulus sources that emulate the in-vivo microenvironment. These platforms are typically engraved into an oxygen-permeable transparent material. Fabrication of these materials requires the use of microfabrication strategies, including soft lithography, 3D printing, and injection molding. Here we provide an overview of what is an organ-on-chip platform, where it can be used, what it is composed of, how it can be fabricated, and how it can be operated. In connection with this topic, we also introduce an overview of the recent applications, where different organs are modeled on the microscale using this technology. [ABSTRACT FROM AUTHOR]

Recent advances in anticancer therapy have shown dramatic improvements in clinical outcomes, and adoptive cell therapy has emerged as a type of immunotherapy that can modulate immune responses by transferring engineered immune cells. However, a small percentage of responders and their toxicity remain as challenges. Three-dimensional (3D) in vitro models of the tumor microenvironment (TME) have the potential to provide a platform for assessing and predicting responses to therapy. This paper describes an in vitro 3D tumor model that incorporates clusters of colorectal cancer (CRC) cells around perfusable vascular networks to validate immune-cell-mediated cytotoxicity against cancer cells. The platform is based on an injection-molded 3D co-culture model and composed of 28 microwells where separate identical vascularized cancer models can be formed. It allows robust hydrogel patterning for 3D culture that enables high-throughput experimentation. The uniformity of the devices resulted in reproducible experiments that allowed 10× more experiments to be performed when compared to conventional polydimethylsiloxane (PDMS)-based microfluidic devices. To demonstrate its capability, primary natural killer (NK) cells were introduced into the vascularized tumor network, and their activities were monitored using live-cell imaging. Extravasation, migration, and cytotoxic activity against six types of CRC cell lines were tested and compared. The consensus molecular subtypes (CMS) of CRC with distinct immune responses resulted in the highest NK cell cytotoxicity against CMS1 cancer cells. These results show the potential of our vascularized tumor model for understanding various steps involved in the immune response for the assessment of adoptive cell therapy. [ABSTRACT FROM AUTHOR]

In vitro models are becoming more advanced to truly present physiological systems while enabling high‐throughput screening and analysis. Organ‐on‐a‐chip devices provide remarkable results through the reconstruction of a three‐dimensional (3D) cellular microenvironment although they need to be further developed in terms of multiple liquid patterning principle, material properties, and scalability. Here we present a 3D anchor‐based microfluidic injection‐molded plastic array culture platform (Anchor‐IMPACT) that enables selective, space‐intensive patterning of hydrogels using anchor‐island for high‐throughput angiogenesis evaluation model. Anchor‐IMPACT consists of a central channel and an anchor‐island, integrating the array into an abbreviated 96‐well plate format with a standard microscope slide size. The anchor‐island enables selective 3D cell patterning without channel‐to‐channel contact or any hydrogel injection port using an anchor structure unlike conventional culture compartment. The hydrogel was patterned into defined regions by spontaneous capillary flow under hydrophilic conditions. We configured multiple cell patterning structures to investigate the angiogenic potency of colorectal cancer cells in Anchor‐IMPACT and the morphological properties of the angiogenesis induced by the paracrine effect were evaluated. In addition, the efficacy of anticancer drugs against angiogenic sprouts was verified by following dose‐dependent responses. Our results indicate that Anchor‐IMPACT offers not only a model of high‐throughput experimentation but also an advanced 3D cell culture platform and can significantly improve current in vitro models while providing the basis for developing predictive preclinical models for biopharmaceutical applications. [ABSTRACT FROM AUTHOR]

In vivo, blood vessels constitutively experience mechanical stresses exerted by adjacent tissues and other structural elements. Vascular collapse, a structural failure of vascular tissues, may stem from any number of possible compressive forces ranging from injury to tumor growth and can promote inflammation. In particular, endothelial cells are continuously exposed to varying mechanical stimuli, internally and externally, resulting in blood vessel deformation and injury. This study proposed a method to model biomechanical-stimuli-induced blood vessel compression in vitro within a polydimethylsiloxane (PDMS) microfluidic 3D microvascular tissue culture platform with an integrated pneumatically actuated compression mechanism. 3D microvascular tissues were cultured within the device. Histological reactions to compressive forces were quantified and shown to be the following: live/dead assays indicated the presence of a microvascular dead zone within high-stress regions and reactive oxygen species (ROS) quantification exhibited a stress-dependent increase. Fluorescein isothiocyanate (FITC)-dextran flow assays showed that compressed vessels developed structural failures and increased leakiness; finite element analysis (FEA) corroborated the experimental data, indicating that the suggested model of vascular tissue deformation and stress distribution was conceptually sound. As such, this study provides a powerful and accessible in vitro method of modeling microphysiological reactions of microvascular tissues to compressive stress, paving the way for further studies into vascular failure as a result of external stress. [ABSTRACT FROM AUTHOR]

The fuel efficiencies of Hybrid Electric Vehicles (HEVs) depend heavily on the control concepts, especially on energy management strategies, because the system efficiency of the vehicle is determined by the exploitation of the electric energy. Control concepts based on optimal control theories like Dynamic Programming (DP) or Pontryagin's Minimum Principle (PMP) have been widely studied over the last two decades, and it has been proven that these control concepts provide near-optimal solutions if future driving conditions are given prior to actual driving. However, it is difficult to apply to real vehicles unless the future driving conditions are known. In this paper, a well-known control strategy based on PMP has been developed, which needs only current driving conditions. The significance of the study is that the control concept introduced herein was evaluated in the IEEE VTS Challenge 2018 competition. It produced the best results in terms of the total energy consumption, where 52 controllers had been competing to minimize the energy consumption in unknown driving cycles. Although the control system was designed from traditional PMP-based control, it becomes a practicable and effective solution by using an adaptive concept for balancing State Of Charge (SOC) of a battery. This study is an extended version of the study presented during IEEE VPPC 2018 and provides the development process of the control concept used in the controller during the IEEE VTS Challenge 2018. [ABSTRACT FROM AUTHOR]

The field of microfluidics-based three-dimensional (3D) cell culture system is rapidly progressing from academic proof-of-concept studies to valid solutions to real-world problems. Polydimethylsiloxane (PDMS)-based platform has been widely adopted as in vitro platforms for mimicking tumor microenvironment. However, PDMS has not been welcomed as a standardized commercial application for preclinical screening due to inherent material limitations that make it difficult to scale-up production. Here, we present an injection-molded plastic array 3D spheroid culture platform (Sphero-IMPACT). The platform is made of polystyrene (PS) in a standardized 96-well plate format with a user-friendly interface. This interface describes a simpler design that incorporates a tapered hole in the center of the rail to pattern a large spheroid with 3D extracellular matrix and various cell types. This hole is designed to accommodate standard pipette tip for automated system. The platform that mediate open microfluidics allows implement spontaneous fluid patterning with high repeatability from the end user. To demonstrate versatile use of the platform, we developed 3D perfusable blood vessel network and tumor spheroid assays. In addition, we established a tumor spheroid induced angiogenesis model that can be applicable for drug screening. Sphero-IMPACT has the potential to provide a robust and reproducible in vitro assay related to vascularized cancer research. This easy-to-use, ready-to-use platform can be translated into an enhanced preclinical model that faithfully reflects the complex tumor microenvironment. [ABSTRACT FROM AUTHOR]

Microphysiological systems have emerged in the last decade to provide an alternative to in vivo models in basic science and pharmaceutical research. In the field of vascular biology, in particular, there has been a lack of a suitable in vitro model exhibiting a three-dimensional structure and the physiological function of vasculature integrated with organ-on-a-chip models. The rapid development of organ-on-a-chip technology is well positioned to fulfill unmet needs. Recently, functional integration of vasculature with diverse microphysiological systems has been increasing. This recent trend corresponds to emerging research interest in how the vascular system contributes to various physiological and pathological conditions. This innovative platform has undergone significant development, but adoption of this technology by end-users and researchers in biology is still a work in progress. Therefore, it is critical to focus on simplification and standardization to promote the distribution and acceptance of this technology by the end-users. In this review, we will introduce the latest developments in vascularized microphysiological systems and summarize their outlook in basic research and drug screening applications. [ABSTRACT FROM AUTHOR]

Polydimethylsiloxane (PDMS) has been widely used in fabricating microfluidic devices for prototyping and proof-of-concept experiments. Due to several material limitations, PDMS has not been widely adopted for commercial applications that require large-scale production. This paper describes a novel injection-molded plastic array 3D culture (IMPACT) platform that incorporates a microfluidic design to integrate patterned 3D cell cultures within a single 96-well (diameter = 9 mm) plate. Cell containing gels can be sequentially patterned by capillary-guided flow along the corner and narrow gaps designed within the 96-well form factor. Compared to PDMS-based hydrophobic burst valve designs, this work utilizes hydrophilic liquid guides to obtain rapid and reproducible patterned gels for co-cultures. When a liquid droplet (i.e. cell containing fibrin or collagen gel) is placed on a corner, spontaneous patterning is achieved within 1 second. Optimal dimensionless parameters required for successful capillary loading have been determined. To demonstrate the utility of the platform for 3D co-culture, angiogenesis experiments were performed by patterning HUVEC (human umbilical endothelial cells) and LF (lung fibroblasts) embedded in 3D fibrin gels. The angiogenic sprouts (with open lumen tip cells expressing junctional proteins) are comparable to those observed in PDMS based devices. The IMPACT device has the potential to provide a robust high-throughput experimental platform for vascularized microphysiological systems. [ABSTRACT FROM AUTHOR]

Liquid patterning is a quintessential aspect in cell-based screening. While there are a variety of methods to handle microliquids utilizing surface treatments, complex microfluidic systems, and automated dispensing, most of the stated methods are both expensive and difficult to implement. Here, we present a fast multi-scale microliquid-patterning method on an open surface using embossed microstructures without surface modification. Arrays of micropillars can trap microliquids when a bulk drop is swept by an elastic sweeper on polystyrene (PS) substrates. The patterning mechanism on a basic form of a 2 × 2 rectangular array of circular pillars is analyzed theoretically and verified with experiments. Nanoliter-to-microliter volumes of liquids are patterned into various shapes by arranging the pillars based on the analysis. Furthermore, an array of geometrically modified pillars can capture approximately 8000 droplets on a large substrate (55 mm × 55 mm) in one step. Given the simplistic method of wipe patterning, the proposed platform can be utilized in both manual benchtop and automated settings. We will provide proof of concept experiments of single colony isolation using nanoliter-scale liquid patterning and of human angiogenic vessel formation using sequential patterning of microliter-scale liquids. [ABSTRACT FROM AUTHOR]

In this study, we propose a practical approach for designing an automobile body in white using multiple materials. This approach includes design optimization to reduce the weight subject to bending and torsional stiffness constraints in a real application considering realistic limitations on the product development time. Whereas conventional bodies in white are at present composed of only steel, we reduce the weight by using steel and aluminium. Although there have been many studies related to body-in-white design, practical design processes have rarely considered the whole vehicle body owing to the difficulties in handling the large number of design variables. Therefore, the proposed design optimization strategy consists of two levels: on the first level, many design variables are screened for significance and, on the second level, the significant design variables are optimized. The screening drastically reduces the number of design variables, from 195 to 81, allowing efficient optimization on the second level. By using this approach, the weight of a reference body in white was reduced by 27.3% while satisfying all the design requirements. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: O-GlcNAcylation plays a role as a metabolic sensor regulating cellular signalling, transcription and metabolism. Transcription factors and signalling pathways related to metabolism are modulated by N-acetyl-glucosamine ( O-GlcNAc) modification. Aberrant regulation of O-GlcNAcylation is closely linked to insulin resistance, type 2 diabetes and obesity. Current evidence shows that increased O-GlcNAcylation negatively regulates insulin signalling, which is associated with insulin resistance and type 2 diabetes. Here, we aimed to evaluate the effects of Oga (also known as Mgea5) haploinsufficiency, which causes hyper- O-GlcNAcylation, on metabolism. Methods: We examined whether Oga mice developed insulin resistance. Metabolic variables were determined including body weight, glucose and insulin tolerance, metabolic rate and thermogenesis. Results: Oga deficiency does not affect insulin signalling even at hyper- O-GlcNAc levels. Oga mice are lean with reduced fat mass and improved glucose tolerance. Furthermore, Oga mice resist high-fat diet-induced obesity with ameliorated hepatic steatosis and improved glucose metabolism. Oga haploinsufficiency potentiates energy expenditure through the enhancement of brown adipocyte differentiation from the stromal vascular fraction of subcutaneous white adipose tissue (WAT). Conclusions/interpretation: Our observations suggest that O-GlcNAcase (OGA) is essential for energy metabolism via regulation of the thermogenic WAT program. [ABSTRACT FROM AUTHOR]

C1-Ten is a member of the tensin family of focal adhesion molecules but recent studies suggest it plays a more active role in many biological processes because of its potential association with diabetes and cancers. However, relatively little is known about the regulation of C1-Ten, such as changes in its protein level or cellular localization. The cellular localization of C1-Ten is unique because it is expressed in cytoplasmic puncta but nothing is known about these puncta. Here, we show that p62 sequestrates C1-Ten into puncta, making C1-Ten diffuse into the cytoplasm upon p62 depletion. More importantly, p62-mediated C1-Ten sequestration promoted C1-Ten ubiquitination and proteasomal degradation. p62-mediated protein reduction was specific to C1-Ten, and not other tensins such as tensin1 and tensin3. Thus, our results link cellular localization of C1-Ten to an off-switch site for C1-Ten. Additionally, p62 expression increased but C1-Ten protein decreased during muscle differentiation, supporting a role for p62 as a physiological regulator of C1-Ten. [ABSTRACT FROM AUTHOR]

mTORC1, a kinase complex that is considered a master regulator of cellular growth and proliferation, is regulated by many extra- and intracellular signals. Among these signals, mitochondrial status is known to have an impact on the effects of mTORC1 on cell growth and survival. However, how mitochondrial status affects mTORC1 activity, notably the molecular link, is not fully elucidated. Here, we found that Parkin can interact with and ubiquitinate mTOR. We also identified K2066 and K2306 as Parkin-dependent and mitochondrial stress-induced mTOR ubiquitination residues. This ubiquitination by Parkin is required for maintenance of mTORC1 activity under mitochondrial stress. With regard to the physiological meaning of mTORC1 activity under mitochondrial stress, we suggest that mTORC1 plays a pro-survival role. [ABSTRACT FROM AUTHOR]

A composite blade structure for a 2 MW horizontal axis wind turbine is optimally designed. Design requirements are simultaneously minimizing material cost and blade weight while satisfying the constraints on stress ratio, tip deflection, fatigue life and laminate layup requirements. The stress ratio and tip deflection under extreme gust loads and the fatigue life under a stochastic normal wind load are evaluated. A blade element wind load model is proposed to explain the wind pressure difference due to blade height change during rotor rotation. For fatigue life evaluation, the stress result of an implicit nonlinear dynamic analysis under a time-varying fluctuating wind is converted to the histograms of mean and amplitude of maximum stress ratio using the rainflow counting algorithm Miner's rule is employed to predict the fatigue life. After integrating and automating the whole analysis procedure an evolutionary algorithm is used to solve the discrete optimization problem. [ABSTRACT FROM PUBLISHER]