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After their successful first observing run (September 12, 2015 -January 12, 2016, the Advanced LIGO detectors were upgraded to increase their sensitivity for the second observing run (November 30, 2016 -August 26, 2017. The Advanced Virgo detector joined the second observing run on August 1, 2017. We discuss the updates that happened during this period in the GstLAL-based inspiral pipeline, which is used to detect gravitational waves from the coalescence of compact binaries both in low latency and an offline configuration. These updates include deployment of a zero-latency whitening filter to reduce the over-all latency of the pipeline by up to 32 seconds, incorporation of the Virgo data stream in the analysis, introduction of a single-detector search to analyze data from the periods when only one of the detectors is running, addition of new parameters to the likelihood ratio ranking statistic, increase in the parameter space of the search, and introduction of a template mass-dependent glitch-excision thresholding method.

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Synthetic lethality is a molecular-targeted therapy for selective killing of cancer cells. We exploited a lethal interaction between superoxide dismutase 1 inhibition and Bloom syndrome gene product (BLM) defect for the treatment of colorectal cancer (CRC) cells (HCT 116) with a customized lung cancer screen-1-loaded nanocarrier (LCS-1-NC). The drug LCS-1 has poor aqueous solubility. To overcome its limitations, a customized NC, composed of a magnetite core coated with three polymeric shells, namely, aminocellulose (AC), branched poly(amidoamine), and paraben-PEG, was developed for encapsulating LCS-1. Encapsulation efficiency and drug loading were found to be 74% and 8.2%, respectively. LCS-1-NC exhibited sustained release, with ∼85% of drug release in 24 h. Blank NC (0.5 mg/mL) exhibited cytocompatibility toward normal cells, mainly due to the AC layer. LCS-1-NC demonstrated high killing selectivity (104 times) toward BLM-deficient HCT 116 cells over BLM-proficient HCT 116 cells. Due to enhanced efficacy of the drug using NC, the sensitivity difference for BLM-deficient cells increased to 1.7 times in comparison to that with free LCS-1. LCS-1-NC induced persistent DNA damage and apoptosis, which demonstrates that LCS-1-NC effectively and preferentially killed BLM-deficient CRC cells. This is the first report on the development of a potential drug carrier to improve the therapeutic efficacy of LCS-1 for specific killing of CRC cells having BLM defects.

We investigated whether particles suitable for delivery to alveolar macrophages may provide a means of targeting rapamycin, an inducer of autophagy, to alveolar macrophages as a host-directed antituberculosis agent. Inhalable particles were prepared by spray-drying and characterized using laser scattering and electron microscopy. Their aerodynamic diameter was calculated from bulk and tapped densities. In vitro drug release was studied in PBS containing 1% SDS. In vitro uptake of particles by THP-1 derived macrophages was studied by flow cytometry. Cytotoxicity of the particles toward macrophages and their efficacy against intracellular Mycobacterium tuberculosis were studied using a methyltetrazolium assay and counting bacterial colonies obtained when cell lysates were plated on agar. The encapsulation efficiency was 88.8 ± 1.13% and drug content 22 ± 4% w/w. The particles had a median diameter of 2.88 ± 0.8 μm and appeared as collapsed spheres. Their calculated aerodynamic diameter was about 1 μm. In vitro drug release from the particles was first-order and extended beyond 10 days. Flow cytometry indicated that the particles were taken up by macrophages within 3 h. Macrophages exposed to the particles or rapamycin in solution at a concentration of 100 μg/mL over a 24 h period maintained 79.37 ± 0.72% and 58.33 ± 1.39% viability, respectively. Efficacy studies concluded that particles were more effective in clearing intracellular mycobacteria than rapamycin in solution. It was concluded that the preparation was suitable for formulating as a dry powder inhalation to test efficacy of inhaled, macrophage-targeted rapamycin against TB.