115 research outputs found
Next-to-leading order strong interaction corrections to the Delta F=2 effective Hamiltonian in the MSSM
We compute the next-to-leading order strong interaction corrections to
gluino-mediated Delta F=2 box diagrams in the Minimal Supersymmetric Standard
Model. These corrections are given by two loop diagrams which we have
calculated in three different regularization schemes in the mass insertion
approximation. We obtain the next-to-leading order Wilson coefficients of the
Delta F=2 effective Hamiltonian relevant for neutral meson mixings. We find
that the matching scale uncertainty is largely reduced at the next-to-leading
order, typically from about 10-15% to few percent.Comment: 26 pages, 8 figure
Formation of laser plasma channels in a stationary gas
The formation of plasma channels with nonuniformity of about +- 3.5% has been
demonstrated. The channels had a density of 1.2x10^19 cm-3 with a radius of 15
um and with length >= 2.5 mm. The channels were formed by 0.3 J, 100 ps laser
pulses in a nonflowing gas, contained in a cylindrical chamber. The laser beam
passed through the chamber along its axis via pinholes in the chamber walls. A
plasma channel with an electron density on the order of 10^18 - 10^19 cm-3 was
formed in pure He, N2, Ar, and Xe. A uniform channel forms at proper time
delays and in optimal pressure ranges, which depend on the sort of gas. The
influence of the interaction of the laser beam with the gas leaking out of the
chamber through the pinholes was found insignificant. However, the formation of
an ablative plasma on the walls of the pinholes by the wings of the radial
profile of the laser beam plays an important role in the plasma channel
formation and its uniformity. A low current glow discharge initiated in the
chamber slightly improves the uniformity of the plasma channel, while a high
current arc discharge leads to the formation of overdense plasma near the front
pinhole and further refraction of the laser beam. The obtained results show the
feasibility of creating uniform plasma channels in non-flowing gas targets.Comment: 15 pages, 7 figures, submitted to Physics of Plasma
Giant lysosomes as a chemotherapy resistance mechanism in hepatocellular carcinoma cells
Despite continuous improvements in therapeutic protocols, cancer-related mortality
is still one of the main problems facing public health. The main cause of treatment
failure is multi-drug resistance (MDR: simultaneous insensitivity to different anticancer
agents), the underlying molecular and biological mechanisms of which
include the activity of ATP binding cassette (ABC) proteins and drug
compartmentalisation in cell organelles. We investigated the expression of the main
ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular
carcinoma (HCC) cell lines, and confirmed the accumulation of the yellow anticancer
drug sunitinib in giant (four lines) and small cytoplasmic vacuoles of
lysosomal origin (two lines). ABC expression analyses showed that the main ABC
protein harboured by all of the cell lines was PGP, whose expression was not
limited to the cell membrane but was also found on lysosomes. MTT assays
showed that the cell lines with giant lysosomes were more resistant to sorafenib
treatment than those with small lysosomes (p,0.01), and that verapamil incubation
can revert this resistance, especially if it is administered after drug pre-incubation.
The findings of this study demonstrate the involvement of PGP-positive lysosomes
in drug sequestration and MDR in HCC cell lines. The possibility of modulating this
mechanism using PGP inhibitors could lead to the development of new targeted
strategies to enhance HCC treatment
Correlation of circulating CD133+ progenitor subclasses with a mild phenotype in Duchenne muscular dystrophy patients.
Various prognostic serum and cellular markers have been identified for many diseases, such as cardiovascular diseases and tumor pathologies. Here we assessed whether the levels of certain stem cells may predict the progression of Duchenne muscular dystrophy (DMD)
Late-onset and long-lasting autoimmune neutropenia: An analysis from the Italian Neutropenia Registry
Evidence of Distinct Tumour-Propagating Cell Populations with Different Properties in Primary Human Hepatocellular Carcinoma
Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC) compartments within human hepatocellular carcinoma (HCC).After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ/⁻ mice.The primary cell populations (hcc-1, -2 and -3) and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features.Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution
The contribution of microlensing surveys to the distance scale
In the early nineties several teams started large scale systematic surveys of
the Magellanic Clouds and the Galactic Bulge to search for microlensing
effects. As a by product, these groups have created enormous time-series
databases of photometric measurements of stars with a temporal sampling
duration and accuracy which are unprecedented. They provide the opportunity to
test the accuracy of primary distance indicators, such as Cepheids, RRLyrae
stars, the detached eclipsing binaries, or the luminosity of the red clump. We
will review the contribution of the microlensing surveys to the understanding
of the physics of the primary distance indicators, recent differential studies
and direct distance determinations to the Magellanic Clouds and the Galactic
Bulge.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles',
A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21
pages; uses Kluwer's crckapb.sty LaTeX style file, enclose
Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis
Abstract Objective MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. Methods The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus (SLE) (n = 33) and primary Sjogren's syndrome (pSS) (n = 23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells. Results 30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes. Conclusions Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc
miR-494-3p is a novel tumor driver of lung carcinogenesis
Lung cancer is the leading cause of tumor-related death worldwide and more efforts are needed to elucidate lung carcinogenesis. Here we investigated the expression of 641 miRNAs in lung tumorigenesis in a K-Ras(+/LSLG12Vgeo);RERTn(ert/ert) mouse model and 113 human tumors. The conserved miRNA cluster on chromosome 12qF1 was significantly and progressively upregulated during murine lung carcinogenesis. In particular, miR-494-3p expression was correlated with lung cancer progression in mice and with worse survival in lung cancer patients. Mechanistically, ectopic expression of miR-494-3p in A549 lung cancer cells boosted the tumor-initiating population, enhanced cancer cell motility, and increased the expression of stem cell-related genes. Importantly, miR-494-3p improved the ability of A549 cells to grow and metastasize in vivo, modulating NOTCH1 and PTEN/PI3K/AKT signaling.Overall, these data identify miR-494-3p as a key factor in lung cancer onset and progression and possible therapeutic target
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