341 research outputs found
Deliverable 4.2 Support of joint learing and innovation in grassroots development initiatives: operational quality of arrangements
Special issue editorial - Plasma interactions with Solar System Objects: Anticipating Rosetta, Maven and Mars Orbiter Mission
Within our solar system, the planets, moons, comets and asteroids all have plasma interactions. The interaction depends on the nature of the object, particularly the presence of an atmosphere and a magnetic field. Even the size of the object matters through the finite gyroradius effect and the scale height of cold ions of exospheric origin. It also depends on the upstream conditions, including position within the solar wind or the presence within a planetary magnetosphere. Soon after ESA׳s Rosetta reached comet Churyumov–Gerasimenko, NASA׳s Maven and ISRO׳s Mars Orbiter Mission (MOM) reached Mars, and ESA׳s Venus Express mission was completed, this issue explores our understanding of plasma interactions with comets, Mars, Venus, and moons in the solar system. We explore the processes which characterise the interactions, such as ion pickup and field draping, and their effects such as plasma escape. Papers are based on data from current and recent space missions, modelling and theory, as we explore our local part of the ׳plasma universe׳
Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins
<p>Abstract</p> <p>Background</p> <p>Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the <it>Xiphophorus </it>melanoma model system, a mutated version of the EGF receptor Xmrk (<it>Xiphophorus </it>melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation.</p> <p>Methods</p> <p>Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene <it>FOSL1 </it>was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.</p> <p>Results</p> <p>Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (<it>Fosl1</it>), early growth response 1 (<it>Egr1</it>), osteopontin (<it>Opn</it>), insulin-like growth factor binding protein 3 (<it>Igfbp3</it>), dual-specificity phosphatase 4 (<it>Dusp4</it>), and tumor-associated antigen L6 (<it>Taal6</it>). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that <it>FOSL1</it>, <it>OPN</it>, <it>IGFBP3</it>, <it>DUSP4</it>, and <it>TAAL6 </it>also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of <it>FOSL1 </it>in human melanoma cell lines reduced their proliferation and migration.</p> <p>Conclusion</p> <p>Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.</p
Negative ion chemistry in Titan's upper atmosphere
International audienceThe Electron Spectrometer (ELS), one of the sensors making up the Cassini Plasma Spectrometer (CAPS) revealed the existence of numerous negative ions in Titan's upper atmosphere. The observations at closest approach (not, vert, similar1000 km) show evidence for negatively charged ions up to not, vert, similar10,000 amu/q, as well as two distinct peaks at 22±4 and 44±8 amu/q, and maybe a third one at 82±14 amu/q. We present the first ionospheric model of Titan including negative ion chemistry. We find that dissociative electron attachment to neutral molecules (mostly HCN) initiates the formation of negative ions. The negative charge is then transferred to more acidic molecules such as HC3N, HC5N or C4H2. Loss occurs through associative detachment with radicals (H and CH3). We attribute the three low mass peaks observed by ELS to CN−, C3N−/C4H− and C5N−. These species are the first intermediates in the formation of the even larger negative ions observed by ELS, which are most likely the precursors to the aerosols observed at lower altitudes
Human Melanoma-Associated Mast Cells Display a Distinct Transcriptional Signature Characterized by an Upregulation of the Complement Component 3 That Correlates With Poor Prognosis
Cutaneous melanoma is one of the most aggressive human malignancies and shows increasing incidence. Mast cells (MCs), long-lived tissue-resident cells that are particularly abundant in human skin where they regulate both innate and adaptive immunity, are associated with melanoma stroma (MAMCs). Thus, MAMCs could impact melanoma development, progression, and metastasis by secreting proteases, pro-angiogenic factors, and both pro-inflammatory and immuno-inhibitory mediators. To interrogate the as-yet poorly characterized role of human MAMCs, we have purified MCs from melanoma skin biopsies and performed RNA-seq analysis. Here, we demonstrate that MAMCs display a unique transcriptome signature defined by the downregulation of the FcεRI signaling pathway, a distinct expression pattern of proteases and pro-angiogenic factors, and a profound upregulation of complement component C3. Furthermore, in melanoma tissue, we observe a significantly increased number of C3 MCs in stage IV melanoma. Moreover, in patients, C3 expression significantly correlates with the MC-specific marker TPSAB1, and the high expression of both markers is linked with poorer melanoma survival. In vitro, we show that melanoma cell supernatants and tumor microenvironment (TME) mediators such as TGF-β, IL-33, and IL-1β induce some of the changes found in MAMCs and significantly modulate C3 expression and activity in MCs. Taken together, these data suggest that melanoma-secreted cytokines such as TGF-β and IL-1β contribute to the melanoma microenvironment by upregulating C3 expression in MAMCs, thus inducing an MC phenotype switch that negatively impacts melanoma prognosis
PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity
PDL1 blockade produces remarkable clinical responses,
thought to occur by T cell reactivation
through prevention of PDL1-PD1 T cell inhibitory interactions.
Here, we find that PDL1 cell-intrinsic
signaling protects cancer cells from interferon (IFN)
cytotoxicity and accelerates tumor progression.
PDL1 inhibited IFN signal transduction through a
conserved class of sequence motifs that mediate
crosstalk with IFN signaling. Abrogation of PDL1
expression or antibody-mediated PDL1 blockade
strongly sensitized cancer cells to IFN cytotoxicity
through a STAT3/caspase-7-dependent pathway.
Moreover, somatic mutations found in human carcinomas
within these PDL1 sequence motifs disrupted
motif regulation, resulting in PDL1 molecules with
enhanced protective activities from type I and type
II IFN cytotoxicity. Overall, our results reveal a
mode of action of PDL1 in cancer cells as a first line
of defense against IFN cytotoxicity
Quantum key distribution and 1 Gbit/s data encryption over a single fibre
We perform quantum key distribution (QKD) in the presence of 4 classical
channels in a C-band dense wavelength division multiplexing (DWDM)
configuration using a commercial QKD system. The classical channels are used
for key distillation and 1 Gbps encrypted communication, rendering the entire
system independent from any other communication channel than a single dedicated
fibre. We successfully distil secret keys over fibre spans of up to 50 km. The
separation between quantum channel and nearest classical channel is only 200
GHz, while the classical channels are all separated by 100 GHz. In addition to
that we discuss possible improvements and alternative configurations, for
instance whether it is advantageous to choose the quantum channel at 1310 nm or
to opt for a pure C-band configuration.Comment: 9 pages, 7 figure
The relative and absolute timing accuracy of the EPIC-pn camera on XMM-Newton, from X-ray pulsations of the Crab and other pulsars
Reliable timing calibration is essential for the accurate comparison of
XMM-Newton light curves with those from other observatories, to ultimately use
them to derive precise physical quantities. The XMM-Newton timing calibration
is based on pulsar analysis. However, as pulsars show both timing noise and
glitches, it is essential to monitor these calibration sources regularly. To
this end, the XMM-Newton observatory performs observations twice a year of the
Crab pulsar to monitor the absolute timing accuracy of the EPIC-pn camera in
the fast Timing and Burst modes. We present the results of this monitoring
campaign, comparing XMM-Newton data from the Crab pulsar (PSR B0531+21) with
radio measurements. In addition, we use five pulsars (PSR J0537-69, PSR
B0540-69, PSR B0833-45, PSR B1509-58 and PSR B1055-52) with periods ranging
from 16 ms to 197 ms to verify the relative timing accuracy. We analysed 38
XMM-Newton observations (0.2-12.0 keV) of the Crab taken over the first ten
years of the mission and 13 observations from the five complementary pulsars.
All the data were processed with the SAS, the XMM-Newton Scientific Analysis
Software, version 9.0. Epoch folding techniques coupled with \chi^{2} tests
were used to derive relative timing accuracies. The absolute timing accuracy
was determined using the Crab data and comparing the time shift between the
main X-ray and radio peaks in the phase folded light curves. The relative
timing accuracy of XMM-Newton is found to be better than 10^{-8}. The strongest
X-ray pulse peak precedes the corresponding radio peak by 306\pm9 \mus, which
is in agreement with other high energy observatories such as Chandra, INTEGRAL
and RXTE. The derived absolute timing accuracy from our analysis is \pm48 \mus.Comment: 16 pages, 9 figures. Accepted for publication on A&
Feasibility of quantum key distribution through dense wavelength division multiplexing network
In this paper, we study the feasibility of conducting quantum key
distribution (QKD) together with classical communication through the same
optical fiber by employing dense-wavelength-division-multiplexing (DWDM)
technology at telecom wavelength. The impact of the classical channels to the
quantum channel has been investigated for both QKD based on single photon
detection and QKD based on homodyne detection. Our studies show that the latter
can tolerate a much higher level of contamination from the classical channels
than the former. This is because the local oscillator used in the homodyne
detector acts as a "mode selector" which can suppress noise photons
effectively. We have performed simulations based on both the decoy BB84 QKD
protocol and the Gaussian modulated coherent state (GMCS) QKD protocol. While
the former cannot tolerate even one classical channel (with a power of 0dBm),
the latter can be multiplexed with 38 classical channels (0dBm power each
channel) and still has a secure distance around 10km. Preliminary experiment
has been conducted based on a 100MHz bandwidth homodyne detector.Comment: 18 pages, 5 figure
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