ABSTRACT
GW190425 is the second of two binary neutron star (BNS) merger events to be significantly detected by the Laser Interferometer Gravitational Wave (GW) Observatory (LIGO), Virgo and the ...Kamioka Gravitational Wave (KAGRA) detector network. With a detection only in LIGO Livingston, the skymap containing the source was large and no plausible electromagnetic counterpart was found in real-time searching in 2019. Here, we summarize Asteroid Terrestrial-Impact Last Alert System (ATLAS) and Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) wide-field optical coverage of the skymap beginning within 1 and 3 h, respectively, of the GW190425 merger time. More recently, a potential coincidence between GW190425 and a fast radio burst FRB 20190425A has been suggested, given their spatial and temporal coincidences. The smaller sky localization area of FRB 20190425A and its dispersion measure led to the identification of a likely host galaxy, UGC 10667 at a distance of 141 ± 10 Mpc. Our optical imaging covered the galaxy 6.0 h after GW190425 was detected and 3.5 h after the FRB 20190425A. No optical emission was detected and further imaging at +1.2 and +13.2 d also revealed no emission. If the FRB 20190425A and GW190425 association were real, we highlight our limits on kilonova emission from a BNS merger in UGC 10667. The model for producing FRB 20190425A from a BNS merger involves a supramassive magnetized neutron star spinning down by dipole emission on the time-scale of hours. We show that magnetar-enhanced kilonova emission is ruled out by optical upper limits. The lack of detected optical emission from a kilonova in UGC 10667 disfavours, but does not disprove, the FRB–GW link for this source.
Tumor cells aberrantly express chemokines and/or chemokine receptors, and some may promote tumor growth and metastasis. We examined the expression and function of chemokine receptor CXCR3 in a ...syngeneic murine model of metastatic breast cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell lines examined. All human breast cancer cell lines examined also expressed CXCR3, as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant murine mammary tumor cell line 66.1 resulted in intracellular calcium mobilization and chemotaxis in vitro. To test the hypothesis that tumor metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this antimetastatic activity was compromised in mice depleted of natural killer cells. Systemic administration of AMG487 also inhibited experimental lung metastasis. In contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary tumors was not affected by receptor antagonism. These studies indicate that murine mammary tumor cells express CXCR3 which facilitates the development of lung metastases. These studies also indicate for the first time that a small molecular weight antagonist of CXCR3 has the potential to inhibit tumor metastasis.
Coccolithoviruses employ a suite of glycosphingolipids (GSLs) to successfully infect the globally important coccolithophore Emiliania huxleyi. Lipid rafts, chemically distinct membrane lipid ...microdomains that are enriched in GSLs and are involved in sensing extracellular stimuli and activating signalling cascades through protein–protein interactions, likely play a fundamental role in host–virus interactions. Using combined lipidomics, proteomics and bioinformatics, we isolated and characterized the lipid and protein content of lipid rafts from control E. huxleyi cells and those infected with EhV86, the type strain for Coccolithovirus. Lipid raft‐enriched fractions were isolated and purified as buoyant, detergent‐resistant membranes (DRMs) in OptiPrep density gradients. Transmission electron microscopy of vesicle morphology, polymerase chain reaction amplification of the EhV major capsid protein gene and immunoreactivity to flotillin antisera served as respective physical, molecular and biochemical markers. Subsequent lipid characterization of DRMs via high performance liquid chromatography‐triple quadrapole mass spectrometry revealed four distinct GSL classes. Parallel proteomic analysis confirmed flotillin as a major lipid raft protein, along with a variety of proteins affiliated with host defence, programmed cell death and innate immunity pathways. The detection of an EhV86‐encoded C‐type lectin‐containing protein confirmed that infection occurs at the interface between lipid rafts and cellular stress/death pathways via specific GSLs and raft‐associated proteins.
Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) are indicators of a poor prognosis in breast cancer. Using several independent publicly available breast cancer gene expression ...databases, we investigated other members of the PGE2 pathway. PGE2 is produced by COX-2 and actively exported by multiple drug resistance-associated protein 4 (MRP4) into the extracellular microenvironment, where PGE2 can bind four cognate EP receptors (EP1–EP4) and initiate diverse biological signaling pathways. Alternatively, PGE2 is imported via the prostaglandin transporter (PGT) and metabolized by 15-prostaglandin dehydrogenase (15-PGDH/HPGD). We made the novel observation that MRP4, PGT, and 15-PGDH are differentially expressed among distinct breast cancer molecular subtypes; this finding was confirmed in independent datasets. In triple-negative breast cancer, the observed gene expression pattern (high COX-2, high MRP4, low PGT, and low 15-PGDH) would favor high levels of tumor-promoting PGE2 in the tumor microenvironment that may contribute to the overall poor prognosis of triple-negative breast cancer.
Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most ...cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs released by cells share similar size, biophysical characteristics and even a biogenesis pathway with cell-produced enveloped viruses, making it a challenge to efficiently separate EVs from LVs. Thus, EVs co-purified with LVs during downstream processing, are considered "impurities" in the context of gene and cell therapy. A greater understanding of EVs co-purifying with LVs is needed to enable improved downstream processing. To that end, EVs from an inducible lentivirus producing cell line were studied under two conditions: non-induced and induced. EVs were identified in both conditions, with their presence confirmed by transmission electron microscopy and Western blot. EV cargos from each condition were then further characterized by a multi-omic approach. Nineteen proteins were identified by mass spectrometry as potential EV markers to differentiate EVs in LV preparations. Lipid composition of EV preparations before and after LV induction showed similar enrichment in phosphatidylserine. RNA cargos in EVs showed enrichment in transcripts involved in viral processes and binding functions. These findings provide insights on the product profile of lentiviral preparations and could support the development of improved separation strategies aimed at removing co-produced EVs.
To determine which type of egg-laying hen housing was best for the chickens, the workers in those housing systems, the environment, and society based on food safety and affordability, a combined ...research project involving egg suppliers, food manufacturers, food service representatives, and food retailers, as well as research institutions and nongovernmental organizations, was performed. This study reports the hen health and welfare portion based upon veterinary health inspections and compared mortality rates, skeletal abnormalities, causes of death determined by necropsy, and titers to infectious bronchitis and Newcastle disease viruses. Birds were housed on a preexisting Midwest layer complex, which consisted of conventional cages (CC). New houses were built adjacent to the CC house where enriched colony cages (EC) and an aviary system (AV) were installed. Two flock cycles from housing to 78 wk of age were followed. Total mortality was greatest for AV, while CC and EC birds were similar. Keel bone fractures were greatest for AV, next greatest for EC, and least for CC birds. Other skeletal abnormalities were greatest for AV birds. Birds dying from being caught in the structure, pick out, and persecution was most frequent for AV and next most frequent for EC, but nonexistent with CC birds. Infectious pododermatitis (bumblefoot) was most frequent for AV, next most frequent for EC, and essentially nonexistent for CC birds. There was little to no effect on antibody titers based upon housing type. Based upon these findings, it appears that EC housing is better for the health and welfare of egg-laying chickens than CC or AV housing.
Annual Emiliania huxleyi blooms (along with other coccolithophorid species) play important roles in the global carbon and sulfur cycles. E. huxleyi blooms are routinely terminated by large, ...host-specific dsDNA viruses, (Emiliania huxleyi Viruses; EhVs), making these host-virus interactions a driving force behind their potential impact on global biogeochemical cycles. Given projected increases in sea surface temperature due to climate change, it is imperative to understand the effects of temperature on E. huxleyi's susceptibility to viral infection and its production of climatically active dimethylated sulfur species (DSS). Here we demonstrate that a 3°C increase in temperature induces EhV-resistant phenotypes in three E. huxleyi strains and that successful virus infection impacts DSS pool sizes. We also examined cellular polar lipids, given their documented roles in regulating host-virus interactions in this system, and propose that alterations to membrane-bound surface receptors are responsible for the observed temperature-induced resistance. Our findings have potential implications for global biogeochemical cycles in a warming climate and for deciphering the particular mechanism(s) by which some E. huxleyi strains exhibit viral resistance.
Automated driving technology along with electric propulsion are widely expected to fundamentally change our transport systems. They may not only allow a more productive use of travel time, but will ...likely trigger completely new business models in the mobility market. A key determinant of the future prospects of both existing and new mobility services will be their production costs. Hence, in this research the production costs of various transport modes both today and in an automated-electric future are analyzed. To account for different local contexts, the study is conducted for 17 cities across the globe. The results indicate that high-income countries will benefit the most from vehicle automation, while only smaller changes can be expected in lower-income countries. This is due to the different relative contribution of labor cost to the total cost of current taxi and bus operations. In a likely final state, transportation costs will be largely decoupled from a country’s income level, which will favor productivity in higher-income locations. While this research provides valuable first insights into potential future developments, the underlying assumptions will need to be updated as better information becomes available.
Revolutions in shared mobility services, vehicle electrification, and automated vehicle technology will affect urban traffic patterns, energy use and CO2 emissions, the automotive industry, public ...transportation, and more. This paper examines the monetary costs of these innovations for users in the near-term (approximately 2020) and how they may evolve in the long-term (approximately 2030–2035). We estimate traveler costs for light duty vehicle trips on a per-mile basis, and investigate their sensitivity to vehicle powertrain, vehicle size, travel mode and intensity of vehicle use, and DC charging assumptions. To highlight differences between human and automated driving, we consider only autonomous vehicle scenarios in the long-term. We document three main findings. First, as battery costs continue to drop over the next decade, private battery electric vehicles will become more cost-competitive with internal combustion vehicles; and in high-mileage ridesourcing applications, electric vehicles will be much more cost-competitive. Second, near-term ridesourcing trips will likely remain about 4–5 times the per-mile cost of driving one's own car, while pooled trips cut this factor to around 3. Third, in the long-term automated vehicles may make ridesourcing cheaper than driving one's own vehicle. Even if the manufacturing cost of automated vehicles remains high, this cost will be minor when amortized over a service life of 400,000 miles. These findings are unchanged even with significant variations in assumed future battery and automation costs, electricity (charging) cost, vehicle insurance and maintenance cost, and ridesourcing providers' overhead rates.
•As batteries become cheaper, private battery electric vehicles will become more cost-competitive with internal combustion vehicles. The full monetary cost of battery electric vehicle travel for households will be about equal to that of internal combustion engine vehicles within a few years, and already is for commercial (longer distance) vehicles.•Near-term (ca. 2020) ridesourcing trips, involving drivers, are about 4–5 times the per-mile cost of driving one's own car, while pooled trips cut this factor to around 3.•Assuming that in the long term (2030-2035), automated vehicles are available at a cost of $10,000 more than conventional driven vehicles, the net savings from eliminating the driver will make ridesourcing about 30% cheaper than driving one's own vehicle. Pooled trips will continue to provide savings but the cost advantage is likely to decline as overall costs decline.
Policy and other implications.•For ridesourcing with EVs, the high mileage and associated energy savings could make these vehicles cost effective; the main question is whether range and recharging considerations create obstacles to their use as high mileage vehicles.•Ridesourcing in the near-term may fail competitive without private subsidies and suffer even more if regulations get severe (e.g. AB 5 in California, or Congestion Pricing in NYC). The question is whether public authorities could invest in bike infrastructure to facilitate micromobility providers' business, smooth capping on number of ebikes and scooters allowed per provider, facilitate POOL services, or support providers becoming multi-modal aggregator platforms.•The low cost of ridesourcing with driverless cars might lead to increased VMT. Policy interventions (such as pricing) could be considered to encourage more collective (POOL, High Capacity Vehicles) travel in the future coupled with multi-modal vision that includes micromobility.
Chemical dispersants can be a useful tool to mitigate oil spills. This study examined potential risks to sensitive estuarine species by comparing the toxicity of two dispersants (Corexit
®
EC9500A ...and Finasol
®
OSR 52) individually and in chemically enhanced water-accommodated fractions (CEWAFs) of Louisiana Sweet Crude oil. Acute toxicity thresholds and sublethal biomarker responses were determined in seven species (sheepshead minnow, grass shrimp, mysid, amphipod, polychaete, hard clam, mud snail). Comparing median lethal (LC
50
) values for the dispersants, Finasol was generally more toxic than Corexit and had greater sublethal toxicity (impaired embryonic hatching, increased lipid peroxidation, decreased acetylcholinesterase activity). The nominal concentration-based mean LC
50
for all species tested with Corexit was 150.31 mg/L compared with 43.27 mg/L with Finasol. Comparing the toxicity of the CEWAFs using the nominal concentrations (% CEWAF), Corexit-CEWAFs appeared more toxic than Finasol-CEWAFs; however, when LC
50
values were calculated using measured hydrocarbon concentrations, the Finasol-CEWAFs were more toxic. There was greater dispersion efficiency leading to greater hydrocarbon concentrations measured in the Corexit-CEWAF solutions than in equivalent Finasol-CEWAF solutions. The measured concentration-based mean LC
50
values for all species tested with Corexit-CEWAF were 261.96 mg/L total extractable hydrocarbons (TEH) and 2.95 mg/L total polycyclic aromatic hydrocarbons (PAH), whereas the mean LC
50
values for all species tested with Finasol-CEWAF were 23.19 mg/L TEH and 0.49 mg/L total PAH. Larval life stages were generally more sensitive to dispersants and dispersed oil than adult life stages within a species. These results will help to inform management decisions regarding the use of oil-spill dispersants.
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