131 research outputs found
Stromal SPOCK1 supports invasive pancreatic cancer growth
This research was supported by a
KWF Dutch Cancer Society Research Project Grant
to MFB and HWL (UVA 2012-5607 and UVA 2013-
5932), and continuous AMC Foundation support
ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy
Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (nβ=β184) or gemcitabine monotherapy (nβ=β188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (pβ<β0.0001, nβ=β157 and nβ=β38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, pβ=β0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3βm vs 7.9βm pβ=β0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4βm and 11.2βm, respectively vs 8.3, pβ=β0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit
ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy
This work was supported by KWF Dutch Cancer Society (UVA 2012β5607 and UVA 2013β5932
Innate Immune Function in Placenta and Cord Blood of Hepatitis C β Seropositive Mother-Infant Dyads
Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in βΌ80% of cases following exposure, the rate of mother-to-child transmission (2β6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and Ξ³Ξ΄-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells
A Search for Technosignatures Around 11,680 Stars with the Green Bank Telescope at 1.15-1.73 GHz
We conducted a search for narrowband radio signals over four observing
sessions in 2020-2023 with the L-band receiver (1.15-1.73 GHz) of the 100 m
diameter Green Bank Telescope. We pointed the telescope in the directions of 62
TESS Objects of Interest, capturing radio emissions from a total of ~11,680
stars and planetary systems in the ~9 arcminute beam of the telescope. All
detections were either automatically rejected or visually inspected and
confirmed to be of anthropogenic nature. In this work, we also quantified the
end-to-end efficiency of radio SETI pipelines with a signal injection and
recovery analysis. The UCLA SETI pipeline recovers 94.0% of the injected
signals over the usable frequency range of the receiver and 98.7% of the
injections when regions of dense RFI are excluded. In another pipeline that
uses incoherent sums of 51 consecutive spectra, the recovery rate is ~15 times
smaller at ~6%. The pipeline efficiency affects calculations of transmitter
prevalence and SETI search volume. Accordingly, we developed an improved Drake
Figure of Merit and a formalism to place upper limits on transmitter prevalence
that take the pipeline efficiency and transmitter duty cycle into account.
Based on our observations, we can state at the 95% confidence level that fewer
than 6.6% of stars within 100 pc host a transmitter that is detectable in our
search (EIRP > 1e13 W). For stars within 20,000 ly, the fraction of stars with
detectable transmitters (EIRP > 5e16 W) is at most 3e-4. Finally, we showed
that the UCLA SETI pipeline natively detects the signals detected with AI
techniques by Ma et al. (2023).Comment: 22 pages, 9 figures, submitted to AJ, revise
Verslag van een archeologisch onderzoek in 1995
Dit rapport is het derde jaarverslag van het archeologisch onderzoek op Ockenburgh
Gebruiksvoorwerpen van de Schevingseweg
Deze publicatie is gewijd aan de vele bijzondere vondsten van been en metaal die de opgraving aan de Schevingseweg in Den Haag heeft opgeleverd. Het is de derde monografie die tot nu toe over deze belangrijke site verschenen is
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