The myelin sheath facilitates action potential conduction along the axons, however, the mechanism by which myelin maintains the spatiotemporal fidelity and limits the hyperexcitability among myelinated neurons requires further investigation. Therefore, in this study, the model of quantum tunneling of potassium ions through the closed channels is used to explore this function of myelin. According to the present calculations, when an unmyelinated neuron fires, there is a probability of that it will induce an action potential in other unmyelinated neurons, and this probability varies according to the type of channels involved, the channels density in the axonal membrane, and the surface area available for tunneling. The myelin sheath forms a thick barrier that covers the potassium channels and prevents ions from tunneling through them to induce action potential. Hence, it confines the action potentials spatiotemporally and limits the hyperexcitability. On the other hand, lack of myelin, as in unmyelinated neurons or demyelinating diseases, exposes potassium channels to tunneling by potassium ions and induces the action potential. This approach gives different perspectives to look at the interaction between neurons and explains how quantum physics might play a role in the actions occurring in the nervous system. Full article

In this paper, a new semiempirical probability model, allowing for prediction of the composition of multimaterial cold spray coating in dependence on the initial percentage of blend components, is developed and applied. The proposed modeling approach takes into account the deposition efficiencies and the particle sizes of each component of the spraying powder blend. The experimental validation using several Cu/Cr₂C₃NiCr mixtures with different percentages of copper and cermet powders showed that the simulation results were in a good agreement with the experimental data. It was demonstrated that the deposition efficiency of the Cr₂C₃NiCr cermet powder strongly decreased when its mass percentage in the Cu/Cr₂C₃NiCr mixture increased from 5% to 75%. It was also shown that the dependence of the Cr₂C₃NiCr content in the coating on the initial percentage in the blend was nonlinear and the standard rule of mixtures was not applicable for prediction of copper–cermet coating composition. Full article

Many latrine campaigns in developing countries fail to be sustained because the introduced latrine is not appropriate to local socio-economic, cultural and environmental conditions, and there is an inadequate community health education component. We tested a low-cost, locally designed and constructed all-weather latrine (the “BALatrine”), together with community education promoting appropriate hygiene-related behaviour, to determine whether this integrated intervention effectively controlled soil-transmitted helminth (STH) infections. We undertook a pilot intervention study in two villages in Central Java, Indonesia. The villages were randomly allocated to either control or intervention with the intervention village receiving the BALatrine program and the control village receiving no program. STH-infection status was measured using the faecal flotation diagnostic method, before and eight months after the intervention. Over 8 months, the cumulative incidence of STH infection was significantly lower in the intervention village than in the control village: 13.4% vs. 27.5% (67/244 vs. 38/283, p < 0.001). The intervention was particularly effective among children: cumulative incidence 3.8% (2/53) for the intervention vs. 24.1% (13/54) for the control village (p < 0.001). The integrated BALatrine intervention was associated with a reduced incidence of STH infection. Following on from this pilot study, a large cluster-randomised controlled trial was commenced (ACTRN12613000523707). Full article

Expression of the small GTPase, Ras-related C3 botulinum toxin substrate 1B (RAC1B), a RAC1-related member of the Rho GTPase family, in tumor tissues of pancreatic ductal adenocarcinoma (PDAC) has been shown previously to correlate positively with patient survival, but the underlying mechanism(s) and the target genes involved have remained elusive. Screening of a panel of established PDAC-derived cell lines by immunoblotting indicated that both RAC1B and Mothers against decapentaplegic homolog 3 (SMAD3) were more abundantly expressed in poorly metastatic and well-differentiated lines as opposed to highly metastatic, poorly differentiated ones. Both siRNA-mediated RAC1B knockdown in the transforming growth factor (TGF)-β-sensitive PDAC-derived cell lines, Panc1 and PaCa3, or CRISPR/Cas-mediated knockout of exon 3b of RAC1 in Panc1 cells resulted in a dramatic decrease in the expression of SMAD3. Unexpectedly, the knockdown of SMAD3 reproduced the promigratory activity of a RAC1B knockdown in Panc1 and PaCa3, but not in TGF-β-resistant BxPC3 and Capan1 cells, while forced expression of SMAD3 alone was able to mimic the antimigratory effect of ectopic RAC1B overexpression in Panc1 cells. Moreover, overexpression of SMAD3 was able to rescue Panc1 cells from the RAC1B knockdown-induced increase in cell migration, while knockdown of SMAD3 prevented the RAC1B overexpression-induced decrease in cell migration. Using pharmacological and dominant-negative inhibition of SMAD3 C-terminal phosphorylation, we further show that the migration-inhibiting effect of SMAD3 is independent of its activation by TGF-β. Finally, we provide evidence that the antimigratory program of RAC1B-SMAD3 in Panc1 cells is executed through upregulation of the migration and TGF-β inhibitor, biglycan (BGN). Together, our data suggest that a RAC1B-SMAD3-BGN axis negatively controls cell migration and that SMAD3 can induce antimigratory genes, i.e., BGN independent of its role as a signal transducer for TGF-β. Therefore, targeting this novel pathway for activation is a potential therapeutic strategy in highly metastatic PDAC to interfere with invasion and metastasis. Full article

Grain boundary (GB) segregation is an important phenomenon that affects many physical properties, as well as microstructure of polycrystals. The segregation of solute atoms on GBs and its effect on GB structure in Al were investigated using two approaches: First principles total energy calculations and the finite temperature large-scale atomistic modeling within hybrid MD/MC approach comprising molecular dynamics and Monte Carlo simulations. We show that the character of chemical bonding is essential in the solute–GB interaction, and that formation of directed quasi-covalent bonds between Si and Zn solutes and neighboring Al atoms causes a significant reconstruction of the GB structure involving a GB shear-migration coupling. For the solutes that are acceptors of electrons in the Al matrix and have a bigger atomic size (such as Mg), the preferred position is determined by the presence of extra volume at the GB and/or reduced number of the nearest neighbors; in this case, the symmetric GB keeps its structure. By using MD/MC approach, we found that GBs undergo significant structural reconstruction during segregation, which can involve the formation of single- or double-layer segregations, GB splitting, and coupled shear-migration, depending on the details of interatomic interactions. Full article

Benzyl isothiocyanate (BITC) is known to inhibit the metastasis of gastric cancer cells but further studies are needed to confirm its chemotherapeutic potential against gastric cancer. In this study, we observed cell shrinkage and morphological changes in one of the gastric adenocarcinoma cell lines, the AGS cells, after BITC treatment. We performed 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2H-tetrazolium bromide (MTT) assay, a cell viability assay, and found that BITC decreased AGS cell viability. Reactive oxygen species (ROS) analyses using 2′,7′-dichlorofluorescin diacetate (DCFDA) revealed that BITC-induced cell death involved intracellular ROS production, which resulted in mitochondrial dysfunction. Additionally, cell viability was partially restored when BITC-treated AGS cells were preincubated with glutathione (GSH). Western blotting indicated that BITC regulated the expressions of the mitochondria-mediated apoptosis signaling molecules, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cytochrome c (Cyt c). In addition, BITC increased death receptor DR5 expression, and activated the cysteine-aspartic proteases (caspases) cascade. Overall, our results showed that BITC triggers apoptosis in AGS cells via the apoptotic pathways involved in ROS-promoted mitochondrial dysfunction and death receptor activation. Full article

Antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism by which antitumor antibodies mediate therapeutic efficacy. At present, we evaluate an Fc-optimized (amino acid substitutions S239D/I332E) FLT3 antibody termed 4G8-SDIEM (FLYSYN) in patients with acute myeloid leukemia (NCT02789254). Here we studied the possibility to induce NK cell ADCC against B-cell acute lymphoblastic leukemia (B-ALL) by Fc-optimized FLT3 antibody treatment. Flow cytometric analysis confirmed that FLT3 is widely expressed on B-ALL cell lines and leukemic cells of B-ALL patients. FLT3 expression did not correlate with that of CD20, which is targeted by Rituximab, a therapeutic monoclonal antibody (mAb) employed in B-ALL treatment regimens. Our FLT3 mAb with enhanced affinity to the Fc receptor CD16a termed 4G8-SDIE potently induced NK cell reactivity against FLT3-transfectants, the B-ALL cell line SEM and primary leukemic cells of adult B-ALL patients in a target-antigen dependent manner as revealed by analyses of NK cell activation and degranulation. This was mirrored by potent 4G8-SDIE mediated NK cell ADCC in experiments with FLT3-transfectants, the cell line SEM and primary cells as target cells. Taken together, the findings presented in this study provide evidence that 4G8-SDIE may be a promising agent for the treatment of B-ALL, particularly in CD20-negative cases. Full article

Motivated by the growing technology of control and data processing as well as the increasingly complex designs of the new generation of gas turbine engines, a fully automatic control strategy that is capable of dealing with different aspects of operational and safety considerations is required to be implemented on gas turbine engines. An advanced practical control mode satisfaction method for the entire operating envelope of gas turbine engines is proposed in this paper to achieve the optimal transient performance for the engine. A constraint management strategy is developed to generate different controller settings for short-range fighters as well as long-range intercontinental aircraft engines at different operating conditions by utilizing a model predictive control approach. Then, the designed controller is tuned and modified with respect to different realistic considerations including the practicality, physical limitations, system dynamics, and computational efforts. The simulation results from a verified two-spool turbofan engine model and controller show that the proposed method is capable of maneuverability and/or fuel economy optimization indices while satisfying all the predefined constraints successfully. Based on the parameters, natural frequencies, and dynamic behavior of the system, a set of optimized weighting factors for different engine parameters is also proposed to achieve the optimal and safe operation for the engine at different flight conditions. The paper demonstrates the effects of the prediction length and control horizon; adding new constraints on the computational effort and the controller performance are also discussed in detail to confirm the effectiveness and practicality of the proposed approach in developing a fully automatic optimized real-time controller for gas turbine engines. Full article

This paper reports on a complete end-to-end 5G mmWave testbed fully reconfigurable based on a FPGA architecture. The proposed system is composed of a baseband/low-IF processing unit, and a mmWave RF front-end at both TX/RX ends. In particular, the baseband unit design is based on a typical agile digital IF architecture, enabling on-the-fly modulations up to 256-QAM. The real-time 5G mmWave testbed, herein presented, adopts OFDM as the transmission scheme waveform, which was assessed OTA by considering the key performance indicators, namely EVM and BER. A detailed overview of system architecture is addressed together with the hardware considerations taken into account for the mmWave testbed development. Following this, it is demonstrated that the proposed testbed enables real-time multi-stream transmissions of UHD video content captured by nine individual cameras, which is in fact one of the killing applications for 5G. Full article

Silver carbonate (Ag₂CO₃), a common transition metal-based inorganic carbonate, is widely utilized in palladium-catalyzed C–H activations as an oxidant in the redox cycle. Silver carbonate can also act as an external base in the reaction medium, especially in organic solvents with acidic protons. Its superior alkynophilicity and basicity make silver carbonate an ideal catalyst for organic reactions with alkynes, carboxylic acids, and related compounds. This review describes recent reports of silver carbonate-catalyzed and silver carbonate-mediated organic transformations, including cyclizations, cross-couplings, and decarboxylations. Full article

Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration. Full article

: Rangeland desertification is one of the most serious problems threatening the ecological environment and socio-economic development on the eastern Qinghai-Tibet Plateau in China. To combat desertification and reduce its adverse effects, some strategies have been undertaken to stabilize the mobile sand dunes and restore the desertified land. In this study, rangeland desertification with a gradient degree of none, light, medium, severe and extreme was assessed, and short-term effectiveness of different treatments on stabilizing the shifting sand dunes was evaluated by monitoring selected vegetation and soil properties. Results showed that vegetation became thinner and sparser, and soil environment deteriorated significantly under desertification, leading to a poor and low diversity ecosystem. Applying a checkerboard protection strategy in which herb species were planted and using a shrub vegetation planting method without checkerboard protection on mobile dunes for five years, vegetation growth state and soil properties were improved. Soil particles were finer, vegetation restoration was more rapid, and soil nutrient improvement was more apparent at the lower locations of the sand dunes under the checkerboard protection planted with herbs, which performed slightly better in improving soil properties than the shrub planting method alone. A longer time period would be required for vegetation and soils on the sand dunes to be restored to sustain more intensive land use. These findings provide more insight into dune stabilization, allowing effective management in the ecological restoration of desertified rangeland. Full article

The effects of soil and topography on the responses of soil respiration (R_s) to climatic variables must be investigated in the southeastern mountainous areas of China due to the rapid land-use change from forest to agriculture. In this study, we investigated the response of R_s to soil temperature (ST), precipitation over the previous seven days (AP7), and soil water content (SWC) across two hillslopes that had different land uses: a tea garden (TG) and a bamboo forest (BF). Meanwhile, the roles of soil properties including soil clay content and total nitrogen (TN), and topography including elevation, profile curvature (PRC), and slope on the different responses of R_s to these climatic variables were investigated. Results showed that mean R_s on the BF hillslope (2.21 umol C m⁻² s⁻¹) was 1.71 times of that on the TG hillslope (1.29 umol C m⁻² s⁻¹). Soil clay content, elevation, and PRC had negative correlations (p < 0.05) with spatial variation of R_s, and ST was positively correlated (p < 0.01) with temporal variation of R_s on both hillslopes. Across both hillslopes ST explained 33%–73% and AP7 explained 24%–38% of the temporal variations in R_s. The mean temperature sensitivities (Q_10s) of R_s were 2.02 and 3.22, respectively, on the TG and BF hillslopes. The Q₁₀ was positively correlated (p < 0.05) with the temporal mean of SWC and TN, and negatively correlated (p < 0.05) with clay and slope. The mean AP7 sensitivities (a concept similar to Q₁₀) were greatly affected by clay and PRC. When R_s was normalized to that at 10 °C, power or quadratic relationships between R_s and SWC were observed in different sites, and the SWC explained 12%–32% of the temporal variation in R_s. When ST and SWC were integrated and considered, improved explanations (45%–81%) were achieved for the R_s temporal variation. In addition, clay and elevation had vital influences on the responses of R_s to SWC. These results highlight the influences of soil, topographic features, and land use on the spatial variations of the R_s, as well as on the responses of R_s to different climatic variables, which will supplement the understanding of controlling mechanisms of R_s on tea and bamboo land-use types in Southeastern China. Full article