AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions

Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Distributed De La Garza algorithm for load-balancing routing in wireless sensor networks

Large scale wireless sensor networks raise many challenges in the design of efficient and effective routing algorithm due to their complexity and hardware constraints. However, the scalability challenge may be mitigated from a macroscopic perspective. One example is the distributed De la Garza iteration (DDLGI) algorithm for global routing load-balancing, based on a set of partial differential equations iteratively solved by the De la Garza method. We theoretically analyze the parallelism of DDLGI and illustrate that the region of interest may impact the degree of parallelism and error. Furthermore, though DDLGI always converges, the slow convergence and long-range information exchange problems may lead to excess energy consumption in communication. Thus, we propose various enhanced De la Garza routing (E-DLGR) algorithms to alleviate the energy consumption problem by which nodes may exchange less information and only need to exchange information with closer nodes to complete each iteration. Our theoretical analysis and simulation results show that the proposed E-DLGR algorithms may have less transmission overhead, thus further reducing energy consumption, and converge faster while still maintaining adequate accuracy.

     

Identification of the adverse effect of nitrate on the phosphate release rate and improvement of EBPR process models.

The adverse effect of nitrate on the phosphate release rate in the anaerobic phase was observed and was hardly explainable with conventional EBPR process models. Four possible mechanisms were proposed including substrate competition, reduced fermentation, parallel reaction and sequential reaction. Batch experiments were designed and conducted to identify the dominant mechanism. Results showed that the sequential reaction was the only possible mechanism where only denitrification occurred if any nitrate existed in the anaerobic phase. Then the phosphate release following after the nitrate was completely removed. Nitrate inhibition effect was added into the PHA storage rate to incorporate the sequential reaction in the conventional ASM3 plus EAWAG bio-P module (ASM3 + P). Nitrate inhibition coefficient, K(I,NO,PAO) was found to be as low as 0.05 mg/L. This correlated well with experimental observation where no also meant that the anaerobic compartment of a continuous flow reactor could be seriously affected by the residual nitrate contained in the sludge recycle flow. This phenomenon caused overestimation of the phosphate uptake rate and consequently underestimation of PO4(3-) -P concentration. This problem was resolved by incorporation of a nitrate inhibition term in the ASM3 + P for more accurate simulation of the EBPR process.     

Ethylene polymerization over MgO‐supported zirconocene catalysts

Supported zirconcene catalysts on a new support, MgO, were prepared and tested in ethylene polymerization. Three types of impregnation methods were employed to find an optimum supporting method for MgO. The direct impregnation of Cp₂ZrCl₂ on MgO showed low metal loading and polymerization activity, while the catalyst had a higher metal loading and polymerization activity when MgO was treated with methylaluminoxane (MAO) before supporting. Treatment of MgO with MAO during the supporting step invoked two types of catalytic sites, which was evidenced by the bimodal molecular weight distribution of the polymer products. MgO is considered to have potential as a support for metallocenes.     

Reducing cycle times in manufacturing and supply chains by input and service rate smoothing

A key performance parameter of a manufacturing network or supply chain is its cycle time; the time that a typical item spends in the network. A previous simulation study on a semiconductor assembly and test facility showed that cycle times could be reduced by having smooth input and service rates. This suggested that there is a “cycle time principle” that, for a system with a specified throughput or input rate, the shortest cycle times are obtained when the input and service rates do not vary over time. We prove that this principle is true for the M/G/1 and M/M/s queueing systems and Jackson networks. The analysis involves establishing several results on the concavity of waiting time probabilities and the convexity of expected waiting times and queue lengths, as functions of input and service rates. These results also have natural uses in other optimization problems.     

Performance analysis of OFDMA uplink systems with symbol timing misalignment

This letter presents our investigation for the effect of symbol timing errors in orthogonal frequency-division multiple access (OFDMA) uplink systems. We express the symbol timing errors between users as the symbol timing misalignments with respect to the desired user. Then, we derive an explicit expression of the signal-to-noise ratio (SNR) as a function of the maximum value of the symbol timing misalignments. Analyses and simulation results show that, to achieve an SNR of 20 dB, the maximum value of the symbol timing misalignments must be less than the cyclic prefix duration plus 6.25% of the useful symbol duration. Based on the resulting SNR degradation, we evaluate the SNR gain with guard subcarriers in order to mitigate the effect of the symbol timing misalignments.