Bulk heterojunction solar cells have been extensively studied owing to their great potential for cost-effective photovoltaic devices. Although recent advances resulted in the fabrication of ...poly(3-hexylthiophene) (P3HT)/fullerene derivative based solar cells with efficiencies in the range 4.4-5.0%, theoretical calculations predict that the development of novel donor materials with a lower bandgap is required to exceed the power-conversion efficiency of 10%. However, all of the lower bandgap polymers developed so far have failed to reach the efficiency of P3HT-based cells. To address this issue, we synthesized a soluble, intensely coloured platinum metallopolyyne with a low bandgap of 1.85 eV. The solar cells, containing metallopolyyne/fullerene derivative blends as the photoactive material, showed a power-conversion efficiency with an average of 4.1%, without annealing or the use of spacer layers needed to achieve comparable efficiency with P3HT. This clearly demonstrates the potential of metallated conjugated polymers for efficient photovoltaic devices.
Asparagine is a non-essential amino acid since it can either be taken up via the diet or synthesized by asparagine synthetase. Acute lymphoblastic leukemia (ALL) cells do not express asparagine ...synthetase or express it only minimally, which makes them completely dependent on extracellular asparagine for their growth and survival. This dependency makes ALL cells vulnerable to treatment with L-asparaginase, an enzyme that hydrolyzes asparagine. To date, all clinically approved L-asparaginases have significant L-glutaminase co-activity, associated with non-immune related toxic side effects observed during therapy. Therefore, reduction of L-glutaminase co-activity with concomitant maintenance of its anticancer L-asparaginase effect may effectively improve the tolerability of this unique drug. Previously, we designed a new alternative variant of Erwinia chrysanthemi (ErA; Erwinaze) with decreased L-glutaminase co-activity, while maintaining its L-asparaginase activity, by the introduction of three key mutations around the active site (ErA-TM). However, Erwinaze and our ErA-TM variant have very short half-lives in vivo. Here, we show that the fusion of ErA-TM with an albumin binding domain (ABD)-tag significantly increases its in vivo persistence. In addition, we evaluated the in vivo therapeutic efficacy of ABD-ErA-TM in a B-ALL xenograft model of SUP-B15. Our results show a comparable long-lasting durable antileukemic effect between the standard-of-care pegylated-asparaginase and ABD-ErA-TM L-asparaginase, but with fewer co-glutaminase-related acute side effects. Since the toxic side effects of current L-asparaginases often result in treatment discontinuation in ALL patients, this novel ErA-TM variant with ultra-low L-glutaminase co-activity and long in vivo persistence may have great clinical potential.
Adiponectin (APN) is an adipokine which predominantly expresses in adipocytes with neuroprotective and anti-inflammatory effects. We have recently indicated that circulatory trimeric APN can enter ...the brain by crossing the blood-brain barrier (BBB) and modulate microglia-mediated neuroinflammation. Here, we found that the microglial NLR family pyrin domain containing 3 (NLRP3)-inflammasome activation was exacerbated in APN
5xFAD mice in age-dependent manner. The focus of this study was to develop a new and tractable therapeutic approach for treating Alzheimer's disease (AD)-related pathology in 5xFAD mice using peripheral APN gene therapy. We have generated and transduced adeno-associated virus (AAV2/8) expressing the mouse mutated APN gene (APN
) into the liver of 5xFAD mice that generated only low-molecular-weight trimeric APN (APN
). Single dose of AAV2/8-APN
in the liver increased circulatory and cerebral APN levels indicating the overexpressed APN
was able to cross the BBB. Overexpression of APN
decreased both the soluble and fibrillar Aβ in the brains of 5xFAD mice. AAV2/8-APN
treatment reduced Aβ-induced IL-1β and IL-18 secretion by suppressing microglial NLRP3-inflammasome activation. The memory functions improved significantly in AAV-APN
-treated 5xFAD mice with reduction of dystrophic neurites. These findings demonstrate that peripheral gene delivery to overexpress trimeric APN can be a potential therapy for AD.
The use of infrared thermography (IRT) technique combining other remoting sensing techniques such as photogrammetry and unmanned aerial vehicle (UAV) platforms to perform geotechnical studies has ...been attempted by several previous researchers and encouraging results were obtained. However, studies using time-lapse IRT survey via a UAV equipped with a thermal camera are limited. Given the unique setting of Hong Kong, which has a high population living in largely hilly terrain with little natural flat land, steep man-made slopes and natural hillsides have caused significant geotechnical problems which pose hazards to life and facilities. This paper presents the adoption of a time-lapse IRT survey using a UAV in such challenging geotechnical conditions. Snapshot and time-lapse IRT studies of a selected site in Hong Kong, where landslides had occurred were carried out, and visual inspection, photogrammetry, and IRT techniques were also conducted. 3D terrain models of the selected sites were created by using data collected from the photogrammetry and single (snapshot) and continuous monitoring (time-lapse) infrared imaging methods applied in this study. The results have successfully identified various thermal infrared signatures attributed to the existence of moisture patches, seepage, cracks/discontinuities, vegetation, and man-made structures. Open cracks/discontinuities, moisture, vegetation, and rock surfaces with staining can be identified in snapshot thermal image, while the gradient of temperature decay plotted in ln(T) vs. ln(t) enables quantifiable identifications of the above materials via time-lapse thermography and analysis.
We have studied the photocatalytic activity of ZnO tetrapods, ZnO powder, and different ZnO nanoparticles. While nanoparticles with small particle size exhibited higher Brunauer–Emmett–Teller (BET) ...surface area, tetrapods exhibited significantly higher photocatalytic activity for degradation of different dyes. Degradation of four different dyes has been achieved for at least 5 times shorter time for tetrapods compared to nanoparticles (20 nm average particle size). Different ZnO samples have been characterized by variable-temperature photoluminescence and time-resolved photoluminescence measurements, and the relationship between optical properties, native defects, production of the reactive oxygen species, and photocatalytic dye degradation has been discussed.
•A new manufacturing system for mycelium-based biocomposite parts.•A Manufacturing cost model of biocomposite part production.•Optimization of a biocomposite manufacturing system.
A manufacturing ...cost model is created that includes all labor, material and overhead costs for novel mycelium-based biocomposite sandwich structures produced by a commercial firm. This model is implemented through a spreadsheet to calculate the equivalent uniform annual costs (UAC) of all manufacturing facilities. A simulation model of the manufacturing line is then implemented based on all these costs as well as system parameters experimentally measured from real manufacturing operations. The Tabu search method is utilized to search for the best manufacturing configuration including optimal number of machines and workers for each manufacturing step under both the current and projected production situations. The optimal solution can be used by the spreadsheet tool to calculate the net cost of each manufactured part and determine a proper retail price. The manufacturing system presented and associated models can be used by manufacturing personnel to assess the commercial viability of bicomposite parts.
We and others have reported that the anticancer activity of L-asparaginase (ASNase) against asparagine synthetase (ASNS)-positive cell types requires ASNase glutaminase activity, whereas anticancer ...activity against ASNS-negative cell types does not. Here, we attempted to disentangle the relationship between asparagine metabolism, glutamine metabolism, and downstream pathways that modulate cell viability by testing the hypothesis that ASNase anticancer activity is based on asparagine depletion rather than glutamine depletion per se. We tested ASNase wild-type (ASNase
) and its glutaminase-deficient Q59L mutant (ASNase
) and found that ASNase glutaminase activity contributed to durable anticancer activity against xenografts of the ASNS-negative Sup-B15 leukemia cell line in NOD/SCID gamma mice, whereas asparaginase activity alone yielded a mere growth delay. Our findings suggest that ASNase glutaminase activity is necessary for durable, single-agent anticancer activity
, even against ASNS-negative cancer types.
The imbalanced distribution of shared bikes in the dockless bike-sharing system (a typical example of the resource-sharing system), which may lead to potential customer churn and lost profit, ...gradually becomes a vital problem for bike-sharing firms and their users. To resolve the problem, we first formulate the bike-sharing system as a Markovian queueing network with higher-demand nodes and lower-demand nodes, which can provide steady-state probabilities of having a certain number of bikes at one node. A model reduction method is then designed to reduce the complexity of the proposed model. Subsequently, we adopt an operator-based relocation strategy to optimize the reduced network. The objective of the optimization model is to maximize the total profit and act as a decision-making tool for operators to determine the optimal relocation frequency. The results reveal that it is possible for most of the shared bikes to gather at one low-demand node eventually in the long run under the influence of the various arrival rates at different nodes. However, the decrease of the number of bikes at the high-demand nodes is more sensitive to the unequal demands, especially when the size of the network and the number of bikes in the system are large. It may cause a significant loss for operators, to which they should pay attention. Meanwhile, different estimated values of parameters related with revenue and cost affect the optimization results differently.
A critical problem in large neural networks is over parameterization with a large number of weight parameters, which limits their use on edge devices due to prohibitive computational power and ...memory/storage requirements. To make neural networks more practical on edge devices and real-time industrial applications, they need to be compressed in advance. Since edge devices cannot train or access trained networks when internet resources are scarce, the preloading of smaller networks is essential. Various works in the literature have shown that the redundant branches can be pruned strategically in a fully connected network without sacrificing the performance significantly. However, majority of these methodologies need high computational resources to integrate weight training via the back-propagation algorithm during the process of network compression. In this work, we draw attention to the optimization of the network structure for preserving performance despite compression by pruning aggressively. The structure optimization is performed using the simulated annealing algorithm only, without utilizing back-propagation for branch weight training. Being a heuristic-based, non-convex optimization method, simulated annealing provides a globally near-optimal solution to this NP-hard problem for a given percentage of branch pruning. Our simulation results have shown that simulated annealing can significantly reduce the complexity of a fully connected network while maintaining the performance without the help of back-propagation.
Our ultimate goal of in vitro derivation of Schwann cells (SCs) from adult bone marrow stromal cells (BMSCs) is such that they may be used autologously to assist post-traumatic nerve regeneration. ...Existing protocols for derivation of SC-like cells from BMSCs fall short in the stability of the acquired phenotype and the functional capacity to myelinate axons. Our experiments indicated that neuro-ectodermal progenitor cells among the human hBMSCs could be selectively expanded and then induced to differentiate into SC-like cells. Co-culture of the SC-like cells with embryonic dorsal root ganglion neurons facilitated contact-mediated signaling that accomplished the switch to fate-committed SCs. Microarray analysis and in vitro myelination provided evidence that the human BMSC-derived SCs were functionally mature. This was reinforced by repair and myelination phenotypes observable in vivo with the derived SCs seeded into a nerve guide as an implant across a critical gap in a rat model of sciatic nerve injury.
•A protocol for in vitro derivation of fate-committed SCs from human BMSCs•The derived human SCs were functionally capable of myelination in vitro•The derived human SCs guided axonal regrowth and formed compact myelin in vivo
Ying-Shing Chan and colleagues demonstrate that the human bone marrow harbors neuro-ectodermal progenitors that can be enriched, expanded, and directed to differentiate into functionally mature, fate-committed SCs. This work holds promise for further development into an autologous cell source for implantation as a treatment strategy for nerve injuries or peripheral neuropathies.
PDF
