Although the anticancer drugs paclitaxel and doxorubicin are commonly used to treat many solid tumors, their effectiveness is highly variable due to tumor cell resistance. Therefore, it is important to find mechanisms that can be targeted to increase the sensitivity of cancer cells to current chemotherapeutic agents. NIMA-related kinase 2 (Nek2), a serine/threonine kinase is emerging as an important oncogene because of its regulatory role in mitosis. Thus, regulation of the Nek2 expression levels may prove important as a target for cancer treatment. The purpose of our study was to determine whether drug sensitivity was increased in the triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 by using small interfering RNA (siRNA) and antisense oligo-nucleotides (ASOs) against Nek2. To this end, MDA-MB-231 and MDA-MB-468 breast cancer cells transfected with Nek2 siRNA or ASO were exposed to various concentrations of paclitaxel and doxorubicin. Cell viability, cell cycle distribution and apoptosis were evaluated. We observed that drug susceptibility in these transfected cells was dramatically increased compared with either agent alone. FACS results showed that apoptosis was induced in siRNA- and ASO-transfected cells as expected due to the regulatory function of Nek2 in centrosome duplication. Interestingly, the cell cyle was not arrested in transfected cells. We found that siRNA and ASO against Nek2 worked synergistically with paclitaxel and doxorubicin by promoting cell apoptosis. Our results suggest that these drugs in combination with Nek2 siRNA or ASO treatment may improve the sensitivity of cancer cells during chemotherapy treatments.
A layered two-dimensional superconducting material 2H-NbSe is used to build a van der Waals heterostructure, where a proximity-coupled superconducting order can be induced in the interfacing materials. Vertically stacked NbSe-graphene-NbSe is fabricated using van der Waals interlayer coupling, producing defect-free contacts with a high interfacial transparency. The atomically thin graphene layer allows the formation of a highly coherent proximity Josephson coupling between the two NbSe flakes. The temperature dependence of the junction critical current (I) reveals short and ballistic Josephson coupling characteristics that agree with theoretical prediction. The strong Josephson coupling is confirmed by a large junction critical current density of 1.6 × 10 A/cm, multiple Andreev reflections in the subgap structure of the differential conductance, and a magnetic-field modulation of I. This is the first demonstration of strongly proximity-coupled Josephson junctions with extremely clean interfaces in a dry-transfer-stacked van der Waals heterostructure.
Gas hydrates consist of guest gas molecules inside hydrogen-bonded water lattices. Natural gas hydrates are found in offshore and permafrost regions. The large amounts of gas hydrate reserves suggest the potential of gas hydrates as an energy resource if economically viable production methods were developed. The proper understandings of hydrate formation/dissociation are important for the drilling and oil production applications. The investigations of physical and geotechnical properties provide the in-depth understandings of the in-situ hydrate formation mechanism and the associated production technologies. The purpose of this review paper is to provide a starting kit for civil engineers who have recently started the research related to the hydrate development and production and want to have insights on the general trends of the hydrate research and the relevant knowledge needed for their research. Gas hydrate explorations include the geophysical explorations, such as the seismic survey, the borehole logging and the geological and geochemical explorations. Gas hydrate productions require the dissociation of gas hydrates, and the production technologies are categorized based on the dissociation techniques involved: depressurization method, thermal stimulation method, and inhibitor injection method. Establishing safe and efficient gas production technology requires the extensive information on the geotechnical characteristics of hydrate reservoirs. Flow assurances, the integrity of sediment formation and the well bore stability are crucial for the safe and efficient productions of gases from gas hydrates in sediments. The strength and deformation characteristics, the fluid migration characteristics, and the thermal conduction characteristics are key factors for controlling the above.
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