A rubidium gallosilicate with zeolite LTL framework topology has been synthesized under hydrothermal conditions, and the as-synthesized hydrated material was characterized via high-resolution synchrotron X-ray powder diffraction at room temperature. Rb-GaSi-LTL, Rb9.8Ga10.4Si25.6O72·17.5H2O, is hexagonal, space group P6/mmm, with a = 18.6260(1) Å and c = 7.6459(1) Å. The framework model shows complete disordering of Ga and Si in the tetrahedral sites, which is analogous to the framework chemistry of its potassium counterpart, K11Ga10.3Si25.7O72·15.1H2O with a = 18.5525(1) Å and c = 7.5619(1) Å, but contrasts to the proposed preferential aluminum partitioning for the 6-ring sites in the aluminosilicate analogues. Similar to the cation distribution in the potassium analogue, half of the rubidium cations in the unit cell fully occupy the sites associated with the narrow channels on the z = 1/2 plane (sites B and C), whereas the other half fill, on average, five out of the six 8-ring sites in the recessed walls of the main 12-ring channel on the z = 0 plane (site D). All of the water molecules are located along the main 12-ring channels at z = 0, 1/6, 1/3, and 1/2 planes. Water molecules on the latter three planes form clusters within the 12-ring windows confinement via hydrogen bonding to one another and to framework oxygen atoms, while those on the z = 0 plane separate the water clusters by coordinating to the site D cations in the main channel. This partitioning of water molecules in the main channel becomes modulated in the hydrated potassium analogue and seems to be dependent on the chemistry of non-framework cations.
Abstract Introduction Tumor cells growing in the brain are resistant to chemotherapy. We have recently demonstrated that the activation of the endothelin receptors A and B axis is involved in the induction of resistance to chemotherapy by primary brain tumor cells and by brain metastases. Treatment with a dual endothelin receptor antagonist in combination with chemotherapy produced significant therapy of orthotopically growing glioblastoma cells as well as breast cancer and lung cancer brain metastases. Since the milieu of tumors in the brain is hypoxic (0.5% - 1% O2), we investigated whether the chemo-resistance of the tumor cells is linked to hypoxia mediated activation of the endothelin receptor axis. Materials and Methods Human glioma (LN229), breast cancer (MDA231), and lung adenocarcinoma (PC14) cell lines were cultured in DMEM supplemented with 5% FBS. The endothelin receptor A (ETAR) and/or B (ETBR) of cancer cells were knocked down by shRNA. ETAR and ETBR were activated by incubating the tumor cells with exogenous endothelin-1 for 15 minutes or blocked by treating the parental or engineered cells with ETAR-specific antagonist, BQ123 (100nM), and/or ETBR-specific antagonist, BQ788 (100nM), for 2 hours prior to the addition of paclitaxel (5ng/ml), temozolomide (100μg/ml) or cisplatinum (5μg/ml). The cultures were placed into incubators with an atmosphere of 20%, 6% or 1% oxygen for 48 hours (MDA231 cells) or 72 hours (LN229 and PC14 cells). Tumor cells were then plated into 96-well plates to determine chemosensitivity by the MTT assay or into 6-well plates for western blots, or into chamber slides for immunohistochemical analyses. Expression of survival-related proteins such as pETAR, pETBR, pAkt, pMAPK, pNFκB, GSTA5, TWIST1 or Bcl2L1, were then determined. Results Stimulation of parental MDA-231, PC-14, or LN229 cells with exogenous ET-1 induced significant resistance against all tested chemotherapeutic agents. The resistance was abolished only when both the ETAR and ETBR were antagonized by a combination of BQ123 and BQ788. Parental cells cultured under hypoxia were also significantly resistant to chemotherapy and treatment of these cells with BQ123 and BQ788 reversed this resistance. The effects of exogenous ET-1 on the induction of chemo-resistance or BQ123 and BQ788 on restoration of chemo-sensitivity were not found in any cancer cells devoid of ETAR and ETBR. In all cases, the chemo-resistance of tumor cells was associated with increased level of expression of proteins related to cell survival. Conclusion These data suggest that the endothelin receptor axis plays a role in hypoxia induced resistance of cancer cells to chemotherapy. Additional studies are warranted to determine the functional changes of the endothelin receptor axis in hypoxia. Citation Format: Hyun Kyung Yu, Ho Jeong Lee, Fahao Zhang, Qiuyu Wu, Isaiah J. Fidler, Sun Jin Kim. Hypoxia induced resistance to chemotherapy is regulated by the endothelin receptor axis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2943.
High-throughput and rapid screening testing is highly desirable to effectively combat the rapidly evolving COVID-19 pandemic co-presents with influenza and seasonal common cold epidemics. Here, we present a general workflow for iterative development and validation of an antibody-based microarray assay for the detection of a respiratory viral panel: (a) antibody screening to quickly identify optimal reagents and assay conditions, (b) immunofluorescence assay design including signal amplification for low viral titers, (c) assay characterization with recombinant proteins, inactivated viral samples and clinical samples, and (d) multiplexing to detect a panel of common respiratory viruses. Using RT-PCR-confirmed SARS-CoV-2 positive and negative pharyngeal swab samples, we demonstrated that the antibody microarray assay exhibited a clinical sensitivity and specificity of 77.2% and 100%, respectively, which are comparable to existing FDA-authorized antigen tests. Moreover, the microarray assay is correlated with RT-PCR cycle threshold (Ct) values and is particularly effective in identifying high viral titers. The multiplexed assay can selectively detect SARS-CoV-2 and influenza virus, which can be used to discriminate these viral infections that share similar symptoms. Such protein microarray technology is amenable for scale-up and automation and can be broadly applied as a both diagnostic and research tool.
The formation of paramagnetic defect centers in aluminophosphate (AlPO4) molecular sieves with different structures is investigated by electron spin resonance (ESR) spectroscopy. Distinct differences in the position and number of the ESR signals generated by dehydroxylation of AlPO4 molecular sieves under a vacuum of 10-5 Torr at 773 K clearly show that the nature of the paramagnetic defect centers formed is significantly different in the structure type of the molecular sieves. In addition, it is found that the spin concentration of these defects depends strongly on the pore size of the AlPO4 molecular sieves as well as their hydration level before dehydroxylation. The larger ring size the molecular sieve has, the higher spin concentration of paramagnetic defects it shows. Thus, the extra-large-pore VPI-5 shows the highest spin concentration value among the molecular sieves studied here, which corresponds to 6.4 defects per 1000 unit cells. The ESR results obtained from AlPO4-based molecular sieves containing heteroatoms other than aluminum and phosphorus (such as silicon or cobalt) reveal that the formation of paramagnetic defect centers is severely restricted when the amount of heteroatoms in their framework increases. On the basis of the overall ESR results of this study, a reliable mechanism of formation of paramagnetic defect centers in AlPO4 molecular sieves is proposed.
Previously we have reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and consequently are impaired in their ability to perform A-to-I microRNA (miRNA) editing. The effects of A-to-I miRNAs editing on melanoma growth and metastasis are yet to be determined. Here we report that miR-378a-3p is undergoing A-to-I editing only in the non-metastatic but not in metastatic melanoma cells. The function of the edited form is different from its wild-type counterpart. The edited form of miR-378a-3p preferentially binds to the 3'-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotype. Indeed, edited miR-378a-3p but not its WT form inhibits melanoma metastasis in vivo. These results further emphasize the role of RNA editing in melanoma progression.
Due to the ever-growing amount of data produced through versatile hyper-connected networks, in pursuit of the Internet of Everything (IoE), the challenges to derive useful knowledge from these big IoE data have received increasing attention. This research deals with fusing multi-modal data from the IoE networks, in order to efficiently provide a set of highly relevant input data for further high-level data analytics such as machine learning. We propose a functional structure of such a data fusion and implement a system prototype based on Apache Spark. Further, our concept is validated through the experiments using the KDD Cup 1999 data.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)