Purpose
Approximately 40–70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in
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gallium-prostate-specific membrane ...antigen positron emission tomography (
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Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases’ site on outcome after metastasis-directed radiotherapy (MDR).
Methods
Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis.
Results
All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04–47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03–18.30). After a median follow-up of 16 months (1–57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up.
Conclusion
Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.
A volatility basis set (VBS) approach for the simulation of secondary organic aerosol (SOA) formation is incorporated in the online coupled atmospheric model system COSMO-ART and applied over Europe ...during the EUCAARI May 2008 campaign. Organic aerosol performance is improved when compared to the default SOA module of COSMO-ART (SORGAM) against high temporal resolution aerosol mass spectrometer ground measurements. The impact of SOA on the overall radiative budget was investigated. The mean direct surface radiative cooling averaged over Europe is -1.2 W m super(-2), representing approximately 20% of the total effect of aerosols on the radiative budget. However, responses are not spatially correlated with the radiative forcing, due to the nonlinear interactions among changes in particle chemical composition, water content, size distribution and cloud cover. These interactions initiated by the effect of SOA on radiation are found to result even in a positive forcing in specific areas. Further model experiments showed that the availability of nitrogen oxides slightly affects SOA production, but that the aging rate constant used in the VBS approximation and boundary concentrations assumed in the model should be carefully selected. The aging of SOA is found to reduce hourly nitrate levels by up to 30%, while the condensation of inorganic species upon pre-existing, SOA-rich particles results in a monthly average increase of 5% in sulfate and ammonium formation in the accumulation mode.
We present an analysis of the molecular gas distributions in the 29 barred and 15 unbarred spirals in the BIMA CO (J= 1-0) Survey of Nearby Galaxies (SONG). For galaxies that are bright in CO, we ...confirm the conclusion by Sakamoto et al. that barred spirals have higher molecular gas concentrations in the central kiloparsec. The SONG sample also includes 27 galaxies below the CO brightness limit used by Sakamoto et al. Even in these less CO-bright galaxies we show that high central gas concentrations are more common in barred galaxies, consistent with radial inflow driven by the bar. However, there is a significant population of early-type (Sa-Sbc) barred spirals (6 of 19) that have no molecular gas detected in the nuclear region and have very little out to the bar corotation radius. This suggests that in barred galaxies with gas-deficient nuclear regions, the bar has already driven most of the gas within the bar corotation radius to the nuclear region, where it has been consumed by star formation. The median mass of nuclear molecular gas is over 4 times higher in early-type bars than in late-type (Sc-Sdm) bars. Since previous work has shown that the gas consumption rate is an order of magnitude higher in early-type bars, this implies that the early types have significantly higher bar-driven inflows. The lower accretion rates in late-type bars can probably be attributed to the known differences in bar structure between early and late types. Despite the evidence for bar-driven inflows in both early and late Hubble-type spirals, the data indicate that it is highly unlikely for a late-type galaxy to evolve into an early type via bar-induced gas inflow. Nonetheless, secular evolutionary processes are undoubtedly present, and pseudobulges are inevitable; evidence for pseudobulges is likely to be clearest in early-type galaxies because of their high gas inflow rates and higher star formation activity.
The host type I interferon (IFN) response protects against
infections. Other bacterial pathogens inhibit type I IFN-mediated cell signaling; however, the interaction between this signaling pathway ...and
has not been well described. Here, we demonstrate that
inhibits the IFN-β signaling pathway but does not inhibit IFN-γ-mediated cell signaling. The addition of IFN-β to
-infected macrophages limited bacterial growth independently of NOS2 and reactive nitrogen species. The type IV secretion system of
is required to inhibit IFN-β-mediated cell signaling. Finally, we show that the inhibition of the IFN-β signaling pathway occurs downstream of STAT1 and STAT2 phosphorylation. In conclusion, our findings describe a novel host cell signaling pathway inhibited by
via its type IV secretion system.
Understanding how galaxies cease to form stars represents an outstanding challenge for galaxy evolution theories. This process of “star formation quenching” has been related to various causes, ...including active galactic nuclei activity, the influence of large-scale dynamics, and the environment in which galaxies live. In this paper, we present the first results from a follow-up of CALIFA survey galaxies with observations of molecular gas obtained with the APEX telescope. Together with the EDGE-CARMA observations, we collected
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CO observations that cover approximately one effective radius in 472 CALIFA galaxies. We observe that the deficit of galaxy star formation with respect to the star formation main sequence (SFMS) increases with the absence of molecular gas and with a reduced efficiency of conversion of molecular gas into stars, which is in line with the results of other integrated studies. However, by dividing the sample into galaxies dominated by star formation and galaxies quenched in their centres (as indicated by the average value of the H
α
equivalent width), we find that this deficit increases sharply once a certain level of gas consumption is reached, indicating that different mechanisms drive separation from the SFMS in star-forming and quenched galaxies. Our results indicate that differences in the amount of molecular gas at a fixed stellar mass are the primary drivers for the dispersion in the SFMS, and the most likely explanation for the start of star formation quenching. However, once a galaxy is quenched, changes in star formation efficiency drive how much a retired galaxy differs in its star formation rate from star-forming ones of similar masses. In other words, once a paucity of molecular gas has significantly reduced star formation, changes in the star formation efficiency are what drives a galaxy deeper into the red cloud, hence retiring it.
This review will focus on the molecular mechanisms of macrophage activation and desensitization by bacterial lipopolysaccharide (LPS). The most recent advances in the understanding of the function of ...the LPS receptor complex and its role in the development of the septic shock syndrome and endotoxin tolerance will be discussed.
Ice-nucleating particles (INPs) trigger the formation of cloud ice crystals in the atmosphere. Therefore, they strongly influence cloud microphysical and optical properties and precipitation and the ...life cycle of clouds. Improving weather forecasting and climate projection requires an appropriate formulation of atmospheric INP concentrations. This remains challenging as the global INP distribution and variability depend on a variety of aerosol types and sources, and neither their short-term variability nor their long-term seasonal cycles are well covered by continuous measurements. Here, we provide the first year-long set of observations with a pronounced INP seasonal cycle in a boreal forest environment. Besides the observed seasonal cycle in INP concentrations with a minimum in wintertime and maxima in early and late summer, we also provide indications for a seasonal variation in the prevalent INP type. We show that the seasonal dependency of INP concentrations and prevalent INP types is most likely driven by the abundance of biogenic aerosol. As current parameterizations do not reproduce this variability, we suggest a new mechanistic description for boreal forest environments which considers the seasonal variation in INP concentrations. For this, we use the ambient air temperature measured close to the ground at 4.2 m height as a proxy for the season, which appears to affect the source strength of biogenic emissions and, thus, the INP abundance over the boreal forest. Furthermore, we provide new INP parameterizations based on the Ice Nucleation Active Surface Site (INAS) approach, which specifically describes the ice nucleation activity of boreal aerosols particles prevalent in different seasons. Our results characterize the boreal forest as an important but variable INP source and provide new perspectives to describe these new findings in atmospheric models.
Toll-like receptors (TLRs) and proteinase-activated receptors (PARs) function as innate immune biosensors in mucosal epithelial cells (ECs). We previously reported the functional and physical ...interactions between TLR4 and PAR(2). We have extended these findings herein by showing the cooperation between PAR(2) and TLR2, TLR3, or TLR4 for activation of nuclear factor-kappaB-dependent signaling in mucosal EC lines. In contrast, activation of PAR(2) negatively regulated TLR3-dependent antiviral pathway, blunting the expression of TLR3/interferon regulatory factor-3 (IRF-3)-driven genes, as well as activation of IRF-3 and STAT1. Consistent with these in vitro observations, PAR(2)(-/-) and TLR4(-/-) mice, which were refractory to footpad edema induced by PAR(2) agonist peptide, were protected from mouse-adapted H1N1 influenza A virus-induced lethality when compared to wild-type (WT) mice. These data support and extend our recently described, novel model of PAR(2)-TLR4 "receptor cooperativity" and highlight the complexity of signaling integration between heterologous innate immune biosensors.
Toll-like receptor (TLR) 2 has recently been associated with cellular responses to numerous microbial products, including LPS and bacterial lipoproteins. However, many preparations of LPS contain low ...concentrations of highly bioactive contaminants described previously as "endotoxin protein," suggesting that these contaminants could be responsible for the TLR2-mediated signaling observed upon LPS stimulation. To test this hypothesis, commercial preparations of LPS were subjected to a modified phenol re-extraction protocol to eliminate endotoxin protein. While it did not influence the ability to stimulate cells from wild-type mice, repurification eliminated the ability of LPS to activate cells from C3H/HeJ (Lpsd) mice. Additionally, only cell lines transfected with human TLR4, but not human or murine TLR2, acquired responsiveness to both re-extracted LPS and to a protein-free, synthetic preparation of lipid A. These results suggest that neither human nor murine TLR2 plays a role in LPS signaling in the absence of contaminating endotoxin protein.
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