What Powers the Compact Radio Emission in Nearby Elliptical and S0 Galaxies?

Many nearby early-type (elliptical and S0) galaxies contain weak (milli-Jansky level) nuclear radio sources on scales a few hundred parsecs or less. The origin of the radio emission, however, has remained unclear, especially in volume-limited samples that select intrinsically less luminous galaxies. Both active galactic nuclei and nuclear star formation have been suggested as possible mechanisms for producing the radio emission. This paper utilizes optical spectroscopic information to address this issue. A substantial fraction of the early-type galaxies surveyed with the Very Large Array by Wrobel & Heeschen (1991) exhibits detectable optical emission lines in their nuclei down to very sensitive limits. Comparison of the observed radio continuum power with that expected from the thermal gas traced by the optical emission lines implies that the bulk of the radio emission is nonthermal. Both the incidence and the strength of optical line emission correlate with the radio power. At a fixed line luminosity, ellipticals have stronger radio cores than S0s. The relation between radio power and line emission observed in this sample is consistent with the low-luminosity extension of similar relations seen in classical radio galaxies and luminous Seyfert nuclei. A plausible interpretation of this result is that the weak nuclear sources in nearby early-type galaxies are the low-luminosity counterparts of more powerful AGNs. The spectroscopic evidence supports this picture. Most of the emission-line objects are optically classified as Seyfert nuclei or low-ionization nuclear emission-line regions (LINERs), the majority of which are likely to be accretion-powered sources.Comment: LaTex, 16 pages including embedded figures. Accepted for publication in the Astrophysical Journa

Discovery of Radio Outbursts in the Active Nucleus of M81

The low-luminosity active galactic nucleus of M81 has been monitored at centimeter wavelengths since early 1993 as a by-product of radio programs to study the radio emission from Supernova 1993J. The extensive data sets reveal that the nucleus experienced several radio outbursts during the monitoring period. At 2 and 3.6 cm, the main outburst occurred roughly in the beginning of 1993 September and lasted for approximately three months; at longer wavelengths, the maximum flux density decreases, and the onset of the burst is delayed. These characteristics qualitatively resemble the standard model for adiabatically expanding radio sources, although certain discrepancies between the observations and the theoretical predictions suggest that the model is too simplistic. In addition to the large-amplitude, prolonged variations, we also detected milder changes in the flux density at 3.6 cm and possibly at 6 cm on short (less than 1 day) timescales. We discuss a possible association between the radio activity and an optical flare observed during the period that the nucleus was monitored at radio wavelengths.Comment: To appear in The Astronomical Journal. Latex, 18 pages including embedded figures and table

Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology

Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. These may especially benefit the management of pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high cancer stem cell (CSC) content and high density of stromal cells and extracellular matrix (ECM). To date, these features are only partially reproduced ex vivo using organoid and sphere cultures. We have now developed a more comprehensive and highly tuneable ex vivo model of PDAC based on the 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumourigenicity. User-defined modification of the system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Indeed, proteomic analysis of these cultures reveals improved matrisome recapitulation compared to organoids. Most importantly, patient-specific in vivo drug responses are better reproduced in self-assembled cultures than in other models. These findings support the use of tuneable self-assembling platforms in cancer research and pave the way for future precision medicine approaches

Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

Author Correction to: The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner (Nature Communications, (2018), 9, 1, (3279), 10.1038/s41467-018-05793-2)

This Article contained an error in the consent of some of the patients used in Figure 4. Following an institute-led investigation within BARTS Cancer Institute post-publication, no documentation of informed consent from the nine lung cancer patients whose blood samples were used in this research project could be recovered and therefore, this data have been removed from the published article.The patients and their families were informed of the original error and apologies were made.The following changes have been made to the paper to remove all mention of the lung cancer samples and the data associated with them.In the abstract, the sentence ‘We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinomapatients with minimal contamination of peripheral blood mononuclear cells.’ has been changed to read ‘We show that rVAR2 efficiently captures CTCs from hepatic, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells

Multiwavelength VLBI observations of Sagittarius A*

The compact radio source Sgr\,A*, associated with the super massive black hole at the center of the Galaxy, has been studied with VLBA observations at 3 frequencies (22, 43, 86\,GHz) performed on 10 consecutive days in May 2007. The total VLBI flux density of Sgr\,A* varies from day to day. The variability is correlated at the 3 observing frequencies with higher variability amplitudes appearing at the higher frequencies. For the modulation indices, we find 8.4\,% at 22\,GHz, 9.3\,% at 43\,GHz, and 15.5\,% at 86\,GHz. The radio spectrum is inverted between 22 and 86\,GHz, suggesting inhomogeneous synchrotron self-absorption with a turnover frequency at or above 86\,GHz. The radio spectral index correlates with the flux density, which is harder (more inverted spectrum) when the source is brighter. The average source size does not appear to be variable over the 10-day observing interval. However, we see a tendency for the sizes of the minor axis to increase with increasing total flux, whereas the major axis remains constant. Towards higher frequencies, the position angle of the elliptical Gaussian increases, indicative of intrinsic structure, which begins to dominate the scatter broadening. At cm-wavelength, the source size varies with wavelength as $\lambda^{2.12\pm0.12}$, which is interpreted as the result of interstellar scatter broadening. After removal of this scatter broadening, the intrinsic source size varies as $\lambda^{1.4 ... 1.5}$. The VLBI closure phases at 22, 43, and 86\,GHz are zero within a few degrees, indicating a symmetric or point-like source structure. In the context of an expanding plasmon model, we obtain an upper limit of the expansion velocity of about 0.1\,c from the non-variable VLBI structure. This agrees with the velocity range derived from the radiation transport modeling of the flares from the radio to NIR wavelengths.}Comment: 14pages, 14 Figures, Accepted for publication in A&

International ocean discovery program expedition 372 preliminary report: Creeping gas hydrate slides and Hikurangi LWD

International Ocean Discovery Program (IODP) Expedition 372 combined two research topics, slow slip events (SSEs) on subduction faults (IODP Proposal 781A-Full) and actively deforming gas hydrate-bearing landslides (IODP Proposal 841-APL). Our study area on the Hikurangi margin, east of the coast of New Zealand, provided unique locations for addressing both research topics.SSEs at subduction zones are an enigmatic form of creeping fault behavior. They typically occur on subduction zones at depths beyond the capabilities of ocean floor drilling. However, at the northern Hikurangi subduction margin they are among the best-documented and shallowest on Earth. Here, SSEs may extend close to the trench, where clastic and pelagic sediments about 1.0-1.5 km thick overlie the subducting, seamount-studded Hikurangi Plateau. Geodetic data show that these SSEs recur about every 2 years and are associated with measurable seafloor displacement. The northern Hikurangi subduction margin thus provides an excellent setting to use IODP capabilities to discern the mechanisms behind slow slip fault behaviour

Quick identification of acute chest pain patients study (QICS)

<p>Abstract</p> <p>Background</p> <p>Patients with acute chest pain are often referred to the emergency ward and extensively investigated. Investigations are costly and could induce unnecessary complications, especially with invasive diagnostics. Nevertheless, chest pain patients have high mortalities. Fast identification of high-risk patients is crucial. Therefore several strategies have been developed including specific symptoms, signs, laboratory measurements, and imaging.</p> <p>Methods/Design</p> <p>The Quick Identification of acute Chest pain Study (QICS) will investigate whether a combined use of specific symptoms and signs, electrocardiography, routine and new laboratory measures, adjunctive imaging including electron beam (EBT) computed tomography (CT) and contrast multislice CT (MSCT) will have a high diagnostic yield for patients with acute chest pain. All patients will be investigated according a standardized protocol in the Emergency Department. Serum and plasma will be frozen for future analysis for a wide range of biomarkers at a later time point. The primary endpoint is the safe recognition of low-risk chest pain patients directly at presentation. Secondary endpoint is the identification of a wide range of sensitive predictive clinical markers, chemical biomarkers and radiological markers in acute chest pain patients. Chemical biomarkers will be compared to quantitative CT measurements of coronary atherosclerosis as a surrogate endpoint. Chemical biomarkers will also be compared in head to head comparison and for their additional value.</p> <p>Discussion</p> <p>This will be a very extensive investigation of a wide range of risk predictors in acute chest pain patients. New reliable fast and cheap diagnostic algorithm resulting from the test results might improve chest pain patients' prognosis, and reduce unnecessary costs and diagnostic complications.</p

ICMSF Methods Studies. XV. Comparison of Four Media and Methods for Enumerating Staphylococcus aureus in Powdered Milk.

Four media were examined for their usefulness in enumerating Staphylococcus aureus inoculated (a) into milk that was then dried or (b) directly into dried milk powder. In all, seven strains of S. aureus were inoculated individually into each preparation and were enumerated after two periods of storage (18 to 19 d and 60 to 61 d). Fourteen laboratories from twelve countries participated in the comparison which found that direct plating on agar medium in 14-cm petri dishes may be as useful as enrichment followed by streaking. Plating on Baird-Parker medium or on Hauschild pork plasma fibrinogen medium and a MPN method using Giolitti and Cantoni's broth with Tween 80 were equally sensitive for enumerating S. aureus in dried milk powder. The use of Hauschild medium may eliminate the need for supplementary tests to confirm colonies as S. aureus , but in some cases was found to fail in some laboratories. Giolitti and Cantoni's broth without Tween 80 generally was less useful than the three other media for enumerating S. aureus . S. aureus inoculated into milk that was then dried survived longer than when inoculated into dried milk

Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7–9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies