This paper gathers arguments and reasons why muons surviving the Gran Sasso mountain cannot mimic the Dark Matter annual modulation signature exploited by the DAMA/NaI and DAMA/LIBRA experiments. A ...number of these items have already been presented in individual papers. Further arguments have been addressed here in order to present a comprehensive collection and to enable a wider community to correctly approach this point.
DAMA/LIBRA results and perspectives Bernabei, R; Belli, P; Cappella, F ...
Journal of physics. Conference series,
07/2018, Letnik:
1056, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The DAMA/LIBRA-phase2 experiment (≃ 250 kg highly radiopure NaI(Tl) equipped with new high quantum efficiency photomultipliers) is in progress in the Gran Sasso National Laboratory of the I.N.F.N.. ...When considering the data collected by DAMA/LIBRA- phase1 and by the former DAMA/NaI experiment (∼ 100 kg of highly radio-pure NaI(Tl)) the data over 14 independent annual cycles, for a total exposure of 1.33 ton × yr, have already been released by exploiting the model-independent Dark Matter (DM) annual modulation signature. Cumulatively a DM annual modulation effect has been observed at 9.3 σ C.L., supporting the presence of DM particles in the galactic halo. No systematic effect or side reaction able to mimic the observed DM annual modulation has been found. Recent corollary analyses in frameworks of Mirror DM candidates and R&D efforts for a possible future DAMA/LIBRA-phase3 are mentioned.
RANKL (receptor activator of NF-κB ligand) is a crucial cytokine for regulating diverse biological systems such as innate immunity, bone homeostasis and mammary gland differentiation, operating ...through activation of its cognate receptor RANK. In these normal physiological processes, RANKL signals through paracrine and/or heterotypic mechanisms where its expression and function is tightly controlled. Numerous pathologies involve RANKL deregulation, such as bone loss, inflammatory diseases and cancer, and aberrant RANK expression has been reported in bone cancer. Here, we investigated the significance of RANK in tumor cells with a particular emphasis on homotypic signaling. We selected RANK-positive mouse osteosarcoma and RANK-negative preosteoblastic MC3T3-E1 cells and subjected them to loss- and gain-of-RANK function analyses. By examining a spectrum of tumorigenic properties, we demonstrate that RANK homotypic signaling has a negligible effect on cell proliferation, but promotes cell motility and anchorage-independent growth of osteosarcoma cells and preosteoblasts. By contrast, establishment of RANK signaling in non-tumorigenic mammary epithelial NMuMG cells promotes their proliferation and anchorage-independent growth, but not motility. Furthermore, RANK activation initiates multiple signaling pathways beyond its canonical target, NF-κB. Among these, biochemical inhibition reveals that Erk1/2 is dominant and crucial for the promotion of anchorage-independent survival and invasion of osteoblastic cells, as well as the proliferation of mammary epithelial cells. Thus, RANK signaling functionally contributes to key tumorigenic properties through a cell-autonomous homotypic mechanism. These data also identify the likely inherent differences between epithelial and mesenchymal cell responsiveness to RANK activation.
Background Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of ...cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. Methods Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. Results Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 p < 0.05), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. Conclusion This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development. Keywords: Circulating tumor cell, Circulating tumor DNA, VX2, Rabbit, Radiation, Head and neck cancer, Oral cavity cancer preclinical model
Some cancers have been stratified into subclasses based on their unique involvement of specific signaling pathways. The mapping of human cancer genomes is revealing a vast number of somatic ...alterations; however, the identification of clinically relevant molecular tumor subclasses and their respective driver genes presents challenges. This information is key to developing more targeted and personalized cancer therapies. Here, we generate a new mouse model of genomically unstable osteosarcoma (OSA) that phenocopies the human disease. Integrative oncogenomics pinpointed cAMP-dependent protein kinase type I, alpha regulatory subunit (Prkar1a) gene deletions at 11qE1 as a recurrent genetic trait for a molecularly distinct subclass of mouse OSA featuring RANKL overexpression. Using mouse genetics, we established that Prkar1a is a bone tumor suppressor gene capable of directing subclass development and driving RANKL overexpression during OSA tumorigenesis. Finally, we uncovered evidence for a PRKAR1A-low subset of human OSA with distinct clinical behavior. Thus, tumor subclasses develop in mice and can potentially provide information toward the molecular stratification of human cancers.
The results obtained with the total exposure of 1.04 ton × yr collected by DAMA/LIBRA–phase1 deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N. during 7 annual cycles ...(i.e. adding a further 0.17 ton × yr exposure) are presented. The DAMA/LIBRA–phase1 data give evidence for the presence of Dark Matter (DM) particles in the galactic halo, on the basis of the exploited model independent DM annual modulation signature by using highly radio-pure NaI(Tl) target, at 7.5
σ
C.L. Including also the first generation DAMA/NaI experiment (cumulative exposure 1.33 ton × yr, corresponding to 14 annual cycles), the C.L. is 9.3
σ
and the modulation amplitude of the
single-hit
events in the (2–6) keV energy interval is: (0.0112±0.0012) cpd/kg/keV; the measured phase is (144±7) days and the measured period is (0.998±0.002) yr, values well in agreement with those expected for DM particles. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade.
The DAMA/LIBRA experiment (~ 250 kg sensitive mass composed by highly radio-pure NaI(Tl)) is in data taking in the underground Laboratory of Gran Sasso (LNGS). The data collected in its first 7 ...annual cycles, corresponding to the so called DAMA/LIBRA-phase1, have been released. Considering also of the former DAMA/NaI experiment (~ 100 kg of highly radio-pure NaI(Tl)) the data of 14 independent annual cycles have been analysed exploiting the model-independent Dark Matter (DM) annual modulation signature (total exposure 1.33 ton × yr). A DM annual modulation effect has been observed at 9.3 σ C.L., thus the presence of DM particles in the galactic halo has been pointed out. No systematic or side reaction able to mimic the observed DM annual modulation has been found or suggested by anyone. At present DAMA/LIBRA is running after an upgrade of the experiment in its phase2 with increased sensitivity.
The wall-pressure fluctuations induced by a compressible subsonic jet over a flat plate are experimentally investigated. Measurements were performed in a semi-anechoic environment, where a ...compressible jet facility, whose nozzle diameter (
D
) was 12 mm, is installed. The position of the flat plate was fixed at
H
/
D
= 2, where
H
is the radial position of the flat plate from the jet axis. The study was carried out for several jet Mach numbers spanning the range from 0.5 to 0.9. An overall aerodynamic characterization of the plate effect on the jet plume is provided by means of Pitot tube measurements. The wall-pressure fluctuations acting on the flat plate were measured by a couple of cavity-mounted pressure transducers, providing pointwise pressure signals in the streamwise and in the spanwise directions. A statistical and spectral characterization of the wall-pressure fluctuation field is provided addressing the effect of the jet Mach number variation and of the spatial evolution along the streamwise and spanwise directions. Implications for wall-pressure fluctuations modelling are discussed by the application of the Corcos’ model. Scaling laws with respect to the different jet flow conditions for the wall-pressure spectra are finally presented.
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