Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Epirubicin to nanodiamonds creates a rapidly synthesized and stable nanodiamond–drug complex that promotes endocytic uptake and enhanced tumor cell retention. These attributes mediate the effective killing of both cancer stem cells and noncancer stem cells in vitro and in vivo. Enhanced treatment of both tumor cell populations results in an improved impairment of secondary tumor formation in vivo compared with treatment by unmodified chemotherapeutics. On the basis of these results, nanodiamond-mediated drug delivery may serve as a powerful method for overcoming chemoresistance in cancer stem cells and markedly improving overall treatment against hepatic cancers.

Chemoresistance is a prevalent issue that accounts for the vast majority of treatment failure outcomes in metastatic cancer. Among the mechanisms of resistance that markedly decrease treatment efficacy, the efflux of drug compounds by ATP-binding cassette (ABC) transporter proteins can impair adequate drug retention by cancer cells required for therapeutic cytotoxic activity. Of note, ABC transporters are capable of effluxing several classes of drugs that are clinical standards, including the anthracyclines such as doxorubicin, as well as anthracenediones such as mitoxantrone. To address this challenge, a spectrum of nanomaterials has been evaluated for improved drug retention and enhanced efficacy. Nanodiamonds (NDs) are emerging as a promising nanomaterial platform because they integrate several important properties into a single agent. These include a uniquely faceted truncated octahedral architecture that enables potent drug binding and dispersibility in water, scalably processed ND particles with uniform diameters of approximately 5 nm, and a demonstrated ability to improve drug tolerance while delaying tumor growth in multiple preclinical models, among others. This work describes a ND–mitoxantrone complex that can be rapidly synthesized and mediates marked improvements in drug efficacy. Comprehensive complex characterization reveals a complex with favorable drug delivery properties that is capable of improving drug retention and efficacy in an MDA-MB-231-luc-D3H2LN (MDA-MB-231) triple negative breast cancer cell line that was lentivirally transduced for resistance against mitoxantrone. Findings from this study support the further evaluation of ND–MTX in preclinical dose escalation and safety studies toward potentially clinical validation.

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Hydrophilic titania (TiO(2)) nanoparticles were dispersed in solutions of polystyrene (PS), and the suspensions were cast on glass surfaces. The effect of drying temperature on the hydrophobic character of PS/TiO(2) was investigated: the static water contact angle increased with the drying temperature, and the as-prepared coating could be adjusted from superhydrophilicity to superhydrophobicity just by controlling the drying temperature. Moreover, the superhydrophobic coating turning into a superhydrophilic one (CA < 5 degrees ) after UV illumination, which can be recovered through being heated.

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With increasing demands for rail passenger and freight operations, sharing a line or track is an economical solution if operational efficiency and track reliability challenges can be accommodated properly. This paper presents findings of ballast layer dynamic responses related to four different freight and passenger car loading patterns studied for four different tie support conditions using the Discrete Element Method (DEM). With the DEM model setup being identical for each support condition, ballast particle contact force networks were visualized first under one dynamic load cycle. Certain load transfer chains were observed associated with all four support conditions. Next, crosstie dynamic velocities were analyzed for all sixteen combinations of the different loading patterns and support conditions. The freight car loads traveling at 50 mph could induce higher crosstie vibration velocities than the lighter passenger car loads traveling at 110 mph and 150 mph in three support conditions: lack of center support, high center binding, and lack of rail seat support. Dynamic movements of ballast particles were visualized in velocity vector plots based on their initial and final centroid coordinates. Results reveal that for the same axle load, higher speeds will cause larger ballast particle movements. However, with higher load magnitudes, larger particle movements can be observed even at lower speeds. Generally, high center binding results in the smallest particle movement while lack of center support presents the largest particle movement. Dynamic load responses of the ballast layer simulations provide insights into evaluating and optimizing tracks to be shared by passenger and freight trains.

This paper presents findings of a railroad ballast study using the discrete element method (DEM) focused on mesoscale performance modeling of ballast layer under different tie support conditions. The simulation assembles ballast gradation that met the requirements of both American Railway Engineering and Maintenance-of-Way Association (AREMA) No. 3 and No. 4A specifications with polyhedral particle shapes created similar to the field-collected ballast samples. A full-track model was generated as a basic model, on which five different support conditions were studied in the DEM simulation. Static rail seat loads of 10 kips (44.5 kN) were applied until the DEM model became stable. The pressure distribution along the tie-ballast interface predicted by DEM simulations was in good agreement with previously published results backcalculated from laboratory testing. Static rail seat loads of 20 kips (89 kN) were then applied in the calibrated DEM model to evaluate in-track performance. Results from the validated full-track DEM simulations indicated that only a small portion of ballast particles participated in load distribution under static loading. Particles on the shoulders and particles in the areas with poor support conditions often experience no or very low contact forces. Load transfer mechanisms investigated through a contact force network varied greatly among different support conditions: lack of rail seat support, full support, and lack of center support had wider force distribution angles than the high center binding and severe center binding conditions. The severe center binding scenario was found to be the most critical support condition in terms of causing the highest tie-ballast contact pressure exceeding 30% of the AREMA allowable pressure.