Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis

Emerging evidence shows that the efficacy of chemotherapeutic drugs are reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated DAMPs (i.e. damage-associated molecular patterns, such as CALR exposure, ATP secretion and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which lead to the activation of NF-κB-mediated CCL2 transcription and IKK2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced ER stress, which triggered PERK activation and eIF2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer

H I content in Coma cluster substructure

Galaxy clusters are some of largest structures in the universe. These very dense environments tend to be home to higher numbers of evolved galaxies that what is found in lower density environments. It is well known that dense environments can influence the evolution of galaxies through the removal of the neutral gas (HI) reservoirs which fuel star formation. It is unclear which environment has a stronger effect: the local environment (i.e. the substructure within the cluster), or the cluster itself. Using the new HI data from the Westerbork Coma Survey, we explore the average HI content of galaxies across the cluster comparing galaxies that reside in substructure to those that do not. We apply to the Dressler-Shectman test to our newly compiled redshift catalogue of the Coma cluster to search for substructure. With so few of the Coma galaxies directly detected in HI, we use the HI stacking technique to probe average HI content below what can be directly detected. Using the Dressler-Shectman test, we find 15 substructures within the footprint of the Westerbork Coma Survey. We compare the average HI content for galaxies within substructure to those not in substructure. Using the HI stacking technique, we find that the Coma galaxies (for which are not detected in HI) are more than 10--50 times more HI deficient than expected which supports the scenario of an extremely efficient and rapid quenching mechanism. By studying the galaxies that are not directly detected in HI, we also find Coma to be more HI deficient than previously thought.Comment: 18 pages (+ 21 page appendix), 23 figures, accepted for publication in A&

Overview of the Development of the Solar Electric Propulsion Technology Demonstration Mission 12.5-kW Hall Thruster

NASA is developing mission concepts for a solar electric propulsion technology demonstration mission. A number of mission concepts are being evaluated including ambitious missions to near Earth objects. The demonstration of a high-power solar electric propulsion capability is one of the objectives of the candidate missions under consideration. In support of NASA's exploration goals, a number of projects are developing extensible technologies to support NASA's near and long term mission needs. Specifically, the Space Technology Mission Directorate Solar Electric Propulsion Technology Demonstration Mission project is funding the development of a 12.5-kilowatt magnetically shielded Hall thruster system to support future NASA missions. This paper presents the design attributes of the thruster that was collaboratively developed by the NASA Glenn Research Center and the Jet Propulsion Laboratory. The paper provides an overview of the magnetic, plasma, thermal, and structural modeling activities that were carried out in support of the thruster design. The paper also summarizes the results of the functional tests that have been carried out to date. The planned thruster performance, plasma diagnostics (internal and in the plume), thermal, wear, and mechanical tests are outlined

The WEBT Campaign on the Blazar 3C279 in 2006

The quasar 3C279 was the target of an extensive multiwavelength monitoring campaign from January through April 2006, including an optical-IR-radio monitoring campaign by the Whole Earth Blazar Telescope (WEBT) collaboration. In this paper we focus on the results of the WEBT campaign. The source exhibited substantial variability of optical flux and spectral shape, with a characteristic time scale of a few days. The variability patterns throughout the optical BVRI bands were very closely correlated with each other. In intriguing contrast to other (in particular, BL Lac type) blazars, we find a lag of shorter- behind longer-wavelength variability throughout the RVB ranges, with a time delay increasing with increasing frequency. Spectral hardening during flares appears delayed with respect to a rising optical flux. This, in combination with the very steep IR-optical continuum spectral index of ~ 1.5 - 2.0, may indicate a highly oblique magnetic field configuration near the base of the jet. An alternative explanation through a slow (time scale of several days) acceleration mechanism would require an unusually low magnetic field of < 0.2 G, about an order of magnitude lower than inferred from previous analyses of simultaneous SEDs of 3C279 and other FSRQs with similar properties.Comment: Accepted for publication in Ap

Electron Beam-Induced Writing of Nanoscale Iron Wires on a Functional Metal Oxide

Electron beam-induced surface activation (EBISA) has been used to grow wires of iron on rutile TiO2(110)-(1 × 1) in ultrahigh vacuum. The wires have a width down to ∼20 nm and hence have potential utility as interconnects on this dielectric substrate. Wire formation was achieved using an electron beam from a scanning electron microscope to activate the surface, which was subsequently exposed to Fe(CO)5. On the basis of scanning tunneling microscopy and Auger electron spectroscopy measurements, the activation mechanism involves electron beam-induced surface reduction and restructuring