Differential effects on membrane permeability and viability of human keratinocyte cells undergoing very low intensity megasonic fields

Among different therapeutic applications of Ultrasound (US), transient membrane sonoporation (SP) - a temporary, non-lethal porosity, mechanically induced in cell membranes through US exposure - represents a compelling opportunity towards an efficient and safe drug delivery. Nevertheless, progresses in this field have been limited by an insufficient understanding of the potential cytotoxic effects of US related to the failure of the cellular repair and to the possible activation of inflammatory pathway. In this framework we studied the in vitro effects of very low-intensity US on a human keratinocyte cell line, which represents an ideal model system of skin protective barrier cells which are the first to be involved during medical US treatments. Bioeffects linked to US application at 1 MHz varying the exposure parameters were investigated by fluorescence microscopy and fluorescence activated cell sorting. Our results indicate that keratinocytes undergoing low US doses can uptake drug model molecules with size and efficiency which depend on exposure parameters. According to sub-cavitation SP models, we have identified the range of doses triggering transient membrane SP, actually with negligible biological damage. By increasing US doses we observed a reduced cells viability and an inflammatory gene overexpression enlightening novel healthy relevant strategies

First results from an aging test of a prototype RPC for the LHCb Muon System

Recent results of an aging test performed at the CERN Gamma Irradiation Facility on a single--gap RPC prototype developed for the LHCb Muon System are presented. The results are based on an accumulated charge of about 0.45 C/cm$^2$, corresponding to about 4 years of LHCb running at the highest background rate. The performance of the chamber has been studied under several photon flux values exploiting a muon beam. A degradation of the rate capability above 1 kHz/cm$^2$ is observed, which can be correlated to a sizeable increase of resistivity of the chamber plates. An increase of the chamber dark current is also observed. The chamber performance is found to fulfill the LHCb operation requirements.Comment: 6 pages, 9 figures, presented at the International Workshop on Aging Phenomena in Gaseous Detectors'', DESY-Hamburg (Germany), October 200

Preliminary results of an aging test of RPC chambers for the LHCb Muon System

The preliminary results of an aging test performed at the CERN Gamma Irradiation Facility on a single--gap RPC prototype developed for the LHCb Muon System are presented. The results are based on an accumulated charge density of 0.42 C/cm^2, corresponding to about 4 years of LHCb running at the highest background rate. We observe a rise in the dark current and noise measured with source off. The current drawn with source on steadily decreased, possibly indicating an increase of resistivity of the chamber plates. The performance of the chamber, studied with a muon beam under several photon flux values, is found to still fulfill the LHCb operation requirements.Comment: 4 pages, 6 figures, presented at RPC2001, VIth Workshop on Resistive Plate Chambers and Related Detectors, November 26-27 2001, Coimbra, Portuga

The twist-bend nematic phase: translational self-diffusion and biaxiality studied by 1H nuclear magnetic resonance diffusometry

Recently, there has been a surge of interest in mesogens exhibiting the twist-bend nematic (NTB) phase that is shown to be chiral even though formed by effectively achiral molecules. Although it now seems to be clear that the NTB phase in the bulk is formed by degenerate domains having opposite handedness, the presence of a supramolecular heliconical structure proposed in the Dozov model has been contradicted by the Hoffmann et al. model in which the heliconical arrangement is replaced by a polar nematic phase. The evidence in support of this is that the quadrupolar splitting tensor measured in various experiments is uniaxial and not biaxial as expected for the twist-bend nematic structure. In this debate, among other evidence, the molecular translational diffusion, and its magnitude with respect to that in the nematic phase above the NTB phase, has also been invoked to eliminate or to confirm one model or the other. We attempt to resolve this issue by reporting the first measurements of the translational self-diffusion coefficients in the nematic and twist-bend nematic phases formed 1″,7″-bis-4-(4′-cyanobiphenyl-4′-yl) heptane (CB7CB). Such measurements certainly appear to resolve the differences between the two models in favour of that for the classic twist-bend nematic phase

Ultrasound delivery of Surface Enhanced InfraRed Absorption active gold-nanoprobes into fibroblast cells: a biological study via Synchrotron-based InfraRed microanalysis at single cell level

Ultrasound (US) induced transient membrane permeabilisation has emerged as a hugely promising tool for the delivery of exogenous vectors through the cytoplasmic membrane, paving the way to the design of novel anticancer strategies by targeting functional nanomaterials to specific biological sites. An essential step towards this end is the detailed recognition of suitably marked nanoparticles in sonoporated cells and the investigation of the potential related biological effects. By taking advantage of Synchrotron Radiation fourier transform infrared micro-spectroscopy (SR-microftiR) in providing highly sensitive analysis at the single cell level, we studied the internalisation of a nanoprobe within fibroblasts (NIH-3T3) promoted by low-intensity US. To this aim we employed 20 nm gold nanoparticles conjugated with the IR marker 4-aminothiophenol. The significant Surface Enhanced Infrared Absorption provided by the nanoprobes, with an absorbance increase up to two orders of magnitude, allowed us to efficiently recognise their inclusion within cells. Notably, the selective and stable SR- microftiR detection from single cells that have internalised the nanoprobe exhibited clear changes in both shape and intensity of the spectral profile, highlighting the occurrence of biological effects. Flow cytometry, immunofluorescence and murine cytokinesis-block micronucleus assays confirmed the presence of slight but significant cytotoxic and genotoxic events associated with the US-nanoprobe combined treatments. our results can provide novel hints towards US and nanomedicine combined strategies for cell spectral imaging as well as drug delivery-based therapies

Per Bocca d'altri. Indios, gesuiti e spagnoli in due documenti segreti sul Perů del XVII secolo

Il volume contiene una serie di testi concernenti lo studio dei Documenti Miccinelli, una serie di manoscritti relativi alla storia del Perù coloniale e alla figura del gesuita Blas Valera

New results from an extensive aging test on bakelite Resistive Plate Chambers

We present recent results of an extensive aging test, performed at the CERN Gamma Irradiation Facility on two single--gap RPC prototypes, developed for the LHCb Muon System. With a method based on a model describing the behaviour of an RPC under high particle flux conditions, we have periodically measured the electrode resistance R of the two RPC prototypes over three years: we observe a large spontaneous increase of R with time, from the initial value of about 2 MOhm to more than 250 MOhm. A corresponding degradation of the RPC rate capabilities, from more than 3 kHz/cm2 to less than 0.15 kHz/cm2 is also found.Comment: 6 pages, 7 figures, presented at Siena 2002, 8th Topical Seminar on Innovative Particle and Radiation Detectors 21-24 October 2002, Siena, Ital

Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections.

Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order to identify novel candidate biological markers for major depression and schizophrenia, we have applied a focused proteomic approach using plasma samples from a large case-control collection. Patients were diagnosed according to DSM criteria using structured interviews and a number of additional clinical variables and demographic information were assessed. Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia. Univariate data analysis showed more significant p-values than would be expected by chance and highlighted several proteins belonging to pathways or mechanisms previously suspected to be involved in the pathophysiology of major depression or schizophrenia, such as insulin and MMP-9 for depression, and BDNF, EGF and a number of chemokines for schizophrenia. Multivariate analysis was carried out to improve the differentiation of cases from controls and identify the most informative panel of markers. The results illustrate the potential of plasma biomarker profiling for psychiatric disorders, when conducted in large collections. The study highlighted a set of analytes as candidate biomarker signatures for depression and schizophrenia, warranting further investigation in independent collections