Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

Cancer metastasis involves the dissemination of cancer cells from the primary tumour site and is responsible for the majority of solid tumour-related mortality. Screening of anti-metastasis drugs often includes functional assays that examine cancer cell invasion inside a three-dimensional hydrogel that mimics the extracellular matrix (ECM). Here, we built a mechanically tuneable collagen hydrogel model to recapitulate cancer spreading into heterogeneous tumour stroma and monitored the three-dimensional invasion of highly malignant breast cancer cells, MDA-MB-231. Migration assays were carried out in the presence and the absence of drugs affecting four typical molecular mechanisms involved in cell migration, as well as under five ECMs with different biophysical properties. Strikingly, the effects of the drugs were observed to vary strongly with matrix mechanics and microarchitecture, despite the little dependence of the inherent cancer cell migration on the ECM condition. Specifically, cytoskeletal contractility-targeting drugs reduced migration speed in sparse gels, whereas migration in dense gels was retarded effectively by inhibiting proteolysis. The results corroborate the ability of cancer cells to switch their multiple invasion mechanisms depending on ECM condition, thus suggesting the importance of factoring in the biophysical properties of the ECM in anti-metastasis drug screenings.     

Elastic lateral buckling of cantilever Litesteel Beams under transverse loading

The LiteSteel Beam (LSB) is a new hollow flange channel section developed by OneSteel Australian Tube Mills using its patented dual electric resistance welding and automated continuous roll-forming technologies. The LSB has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. Its flexural strength for intermediate spans is governed by lateral distortional buckling characterised by simultaneous lateral deflection, twist and web distortion. Recent research on LSBs has mainly focussed on their lateral distortional buckling behaviour under uniform moment conditions. However, in practice, LSB flexural members are subjected to non-uniform moment distributions and load height effects as they are often under transverse loads applied above or below their shear centre. These loading conditions are known to have significant effects on the lateral buckling strength of beams. Many steel design codes have adopted equivalent uniform moment distribution and load height factors based on data for conventional hot-rolled, doubly symmetric I-beams subject to lateral torsional buckling. The non-uniform moment distribution and load height effects of transverse loading on cantilever LSBs, and the suitability of the current design modification factors to include such effects are not known. This paper presents a numerical study based on finite element analyses of the elastic lateral buckling strength of cantilever LSBs subject to transverse loading, and the results. The applicability of the design modification factors from various steel design codes was reviewed, and suitable recommendations are presented for cantilever LSBs subject to transverse loading.     

Increasing the hydrophobic interaction between terminal W-motifs enhances the stability of Salmonella typhimurium sialidase. A general strategy for the stabilization of {beta}-propeller protein fold

Protein engineering of the ß-propeller protein aimedat enhancing the structural stability of the protein was carriedout using a monomeric single domain ß-propeller protein,Salmonella typhimurium sialidase, as a model. Ala53 and Ala69each located at strands B and C of the W1 motif were mutatedto Leu and Val, respectively, to increase the hydrophobic interactionbetween W1 and W6 motifs. The mutants showed enhanced stabilitytowards guanidine hydrochloride and thermal unfolding. Ala53Leushowed higher stability, probably owing to the capability ofthe mutated Leu to interact extensively with more residues involvedin the hydrophobic interactions between the terminal W-motifs.The mutations, which are located far from the active site, haveno significant effect on the enzymatic properties. The strategyto enhance the stability proposed here might be applied to theother ß-propeller proteins.     

Charge Collection From Within a Collecting Junction Well

This paper provides the analytical equation for the charge collection from a collecting region with a finite dimension. Electron-beam-induced current has widely been used for semiconductor characterization. The availability of analytical expressions would further enhance the study and development of various measurement techniques. Nevertheless, most devices are fabricated with junctions that have finite dimensions, which are usually either L shaped or U shaped. For these cases, the analytical expressions are lacking. This paper provides the derivation of the electric current profile when an electron beam scans from within the collecting region for these two cases. The computation was verified with a semiconductor device simulation program on a computer and was found to be in good agreement. This paper then gives a discussion on the effects of certain parameters such as the junction depth and junction width, the diffusion length, and the depth of the generation volume.     

A New Sono-Chemo Sensitizer Overcoming Tumor Hypoxia for Augmented Sono/Chemo-Dynamic Therapy and Robust Immune-Activating Response

Novel sonosensitizers with intrinsic characteristics for tumor diagnosis, efficient therapy, and tumor microenvironment regulation are appealing in current sonodynamic therapy. Herein, a manganese (Mn)-layered double hydroxide-based defect-rich nanoplatform is presented as a new type of sono-chemo sensitizer, which allows ultrasound to efficiently trigger reactive oxygen species generation for enhanced sono/chemo-dynamic therapy. Moreover, such a nanoplatform is able to relieve tumor hypoxia and achieve augmented singlet oxygen production via catalyzing endogenous H₂O₂ into O₂. On top of these actions, the released Mn²⁺ ions and immune-modulating agent significantly intensify immune activation and reverse the immunosuppressive tumor microenvironment to the immunocompetent one. Consequently, this nanoplatform exhibits excellent anti-tumor efficacy and effectively suppresses both primary and distant tumor growth, demonstrating a new strategy to functionalize nanoparticles as sono-chemo sensitizers for synergistic combination cancer therapy.     

Carbon nanotube Schottky diode: an atomic perspective

The electron transport properties of semiconducting carbon nanotube (SCNT) Schottky diodes are investigated with atomic models using density functional theory and the non-equilibrium Green's function method. We model the SCNT Schottky diode as a SCNT embedded in the metal electrode, which resembles the experimental set-up. Our study reveals that the rectification behaviour of the diode is mainly due to the asymmetric electron transmission function distribution in the conduction and valence bands and can be improved by changing metal-SCNT contact geometries. The threshold voltage of the diode depends on the electron Schottky barrier height which can be tuned by altering the diameter of the SCNT. Contrary to the traditional perception, the metal-SCNT contact region exhibits better conductivity than the other parts of the diode.     

Measurement of concrete strength using the emission intensity ratio between Ca(II) 396.8 nm and Ca(I) 422.6 nm in a Nd:YAG laser-induced plasma

An experiment to investigate the potential of a laser-induced plasma method for determining concrete compressive strength was conducted by focusing a Nd:YAG laser on concrete samples with different degrees of compressive strength. This technique was developed in light of the role of the shock wave in the generation of a laser-induced plasma. It was found that the speed of the shock front depends on the hardness of the sample. It was also found that a positive relationship exists between the speed of the shock front and the ionization rate of the ablated atoms. Hence, the ratio of the intensity between the Ca(II) 396.8 nm and Ca(I) 422.6 nm emission lines detected from the laser-induced plasma can be used to examine the hardness of the material. In fact, it was observed that the ratio changes with respect to the change in the concrete compressive strength. The findings also show that the ratio increases with time after the cement is mixed with water.     

Quantitative analysis of deuterium in zircaloy using double-pulse laser-induced breakdown spectrometry (LIBS) and helium gas plasma without a sample chamber

A crucial safety measure to be strictly observed in the operation of heavy-water nuclear power plants is the mandatory regular inspection of the concentration of deuterium penetrated into the zircaloy fuel vessels. The existing standard method requires a tedious, destructive, and costly sample preparation process involving the removal of the remaining fuel in the vessel and melting away part of the zircaloy pipe. An alternative method of orthogonal dual-pulse laser-induced breakdown spectrometry (LIBS) is proposed by employing flowing atmospheric helium gas without the use of a sample chamber. The special setup of ps and ns laser systems, operated for the separate ablation of the sample target and the generation of helium gas plasma, respectively, with properly controlled relative timing, has succeeded in producing the desired sharp D I 656.10 nm emission line with effective suppression of the interfering H I 656.28 nm emission by operating the ps ablation laser at very low output energy of 26 mJ and 1 μs ahead of the helium plasma generation. Under this optimal experimental condition, a linear calibration line is attained with practically zero intercept and a 20 μg/g detection limit for D analysis of zircaloy sample while creating a crater only 10 μm in diameter. Therefore, this method promises its potential application for the practical, in situ, and virtually nondestructive quantitative microarea analysis of D, thereby supporting the more-efficient operation and maintenance of heavy-water nuclear power plants. Furthermore, it will also meet the anticipated needs of future nuclear fusion power plants, as well as other important fields of application in the foreseeable future.