Long-term physical evolution of an elastomeric ultrasound contrast microbubble

Hypothesis: One of the main assets of crosslinked polymer-shelled microbubbles (MBs) as ultrasound-active theranostic agents is the robustness of the shells, combined with the chemical versatility in modifying the surface with ligands and/or drugs. Despite the long shelf-life, subtle modifications occur in the MB shells involving shifts in acoustic, mechanical and structural properties. Experiments: We carried out a long-term morphological and acoustic evolution analysis on elastomeric polyvinyl-alcohol (PVA)-shelled MBs, a novel platform accomplishing good acoustic and surface performances in one agent. Confocal laser scanning microscopy, acoustic spectroscopy and AFM nanomechanics were integrated to understand the mechanism of PVA MBs ageing. The changes in the MB acoustic properties were framed in terms of shell thickness and viscoelasticity using a linearised oscillation theory, and compared to MB morphology and to nanomechanical analysis. Findings: We enlightened a novel, intriguing ageing time evolution of the PVA MBs with double behaviour with respect to a crossover time of ∼50 days. Before, significant changes occur in MB stiffness and shell thickness, mainly due to a massive release of entangled PVA chains. Then, the MB resonance frequency increases together with shell thickening and softening. Our benchmark study is of general interest for emerging viscoelastomeric bubbles towards personalised medicine

Noise in multiple sclerosis: unwanted and necessary

As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression “noise”) can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy

MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia

OBJECTIVE: To evaluate the expression of microRNA (miR)-551b in patients with low and high grade cervical intraepithelial neoplasia (CIN) and to find an association with high-risk Human Papillomavirus (HR-HPV) infection-related prognostic biomarkers. PATIENTS AND METHODS: The expression level of miR-551b was determined in 50 paraffin-embedded cervical specimens (10 normal squamous epithelium, 18 condylomas, 8 CIN1, and 14 CIN2-3) using quantitative Real-time polymerase chain reaction (qRT-PCR). χ2-test compared miR-551b expression in different diagnosis groups. An Ordered Logistic Regression and a Probit correlation were made to correlate miR-551b expression levels with the cervical tissue histological findings. The immunohistochemical distribution of p16 and Ki-67 according to histopathological findings was also assessed. RESULTS: The distribution of the miR-551b expression profile was significantly lower in CIN1-3 samples compared to other histological diagnosis groups (condyloma and negative). The expression levels were inversely correlated to the cervical pathological grade, from negative to CIN2-3. A 1% increase in miR-551b expression level produced an increase of 19% to the probability of a minor histological grade diagnosis in a range from negative to CIN2-3 and an increase of 13% to the probability of a negative histological grade diagnosis. Among the cases with miR-551b expression < 0.02 (considered as cut-off value) a significant statistical correlation was found between p16 and Ki-67 expression and the diagnosis of CIN2-3. CONCLUSIONS: O ur d ata s howed a s ignificant inverse correlation between miR-551b expression and the histological grading of the lesions, suggesting a tumor suppressive function in the different stages of cervical dysplasia

Provenance support for service-based infrastructure

Service-based architectures represent the next evolutionary step in the development of e-science, namely, the transformation of the Internet from a commercial marketplace to a mechanism for sharing multidisciplinary scientific resources. Although scientists in many disciplines have become increasingly reliant on distributed computing technologies for data processing and dissemination, the record of the processing history and origin of a data product, that is its data provenance, is often nonexistent, incomplete or impossible to recover by potential users. This thesis aims to address data provenance issues in service-based environments, particularly to answer how a scientist who performs a workflow execution in such an environment can (1) document the data provenance for a data item created by the execution, and (2) use the provenance documentation as a recipe to re-execute the workflow. This thesis pro poses a provenance model for delivering data provenance support in a service-based environment. Through the use of an example scenario of a scientific workflow in the Astrophysics domain, we explore and identify components of the provenance model. The provenance model proposes a technique to collect and record data provenance for service-based workflow executions. The technique facilitates the collection of data provenance of workflow execution at runtime. In order to record the collected data provenance, the thesis also proposes a specification to represent provenance to de scribe the processing history whereby a piece of data was derived. The thesis also proposes query interfaces that allow recorded provenance to be queried, has formulated a technique to construct provenance graphs, and supports the re-execution of past workflows. The provenance representation specification, the collection technique, and the query interfaces have been used to implement a prototype system to demonstrate the proposed model. The thesis also experimentally evaluates the scalability of the components implemented.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

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

Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features

Internal levels of selected endocrine disruptors (EDs) (i.e., perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di-2-ethylhexyl-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and bisphenol A (BPA)) were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs) of same subjects, gene expression levels of a panel of nuclear receptors (NRs), namely estrogen receptor α (ERα) estrogen receptor β (ERβ), androgen receptor (AR), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptor γ (PPARγ) and pregnane X receptor (PXR) were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERβ, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health

Symptomatic leptomeningeal and intramedullary metastases from intracranial glioblastoma multiforme: A case report

Background. Glioblastoma multiforme infrequently metastasizes to the leptomeninges and even more rarely to the spinal cord. Moreover, very few patients with intracranial glioblastoma develop symptoms from spinal dissemination, with most patients not surviving long enough for spinal disease to become clinically evident. Case report. We present a rare case of symptomatic diffuse spinal leptomeningeal metastases simultaneously to an intramedullary lesion from an intracranial glioblastoma multiforme. After the diagnosis of spinal metastases the patient was treated with limited-field spinal radiotherapy (30 Gy in 3-Gy fractions). Results. Radiotherapy on the main spinal lesions provided either relief from pain or mild improvement of neurological deficits. The patient died due to intracranial progression 4 months after diagnosis of spinal seeding and 17 months after diagnosis of the primary disease. We analyzed leptomeningeal and spinal metastases from glioblastoma multiforme with reference to the literature. Conclusions. Radiotherapy for spinal disease may provide important symptom relief but the prognosis of these patients remains dramatically poor. As the local control of primary glioblastoma multiforme has improved with recent therapeutic advances, distant metastasis from high-grade gliomas is likely to become a more common clinical problem and such patients need to be included in clinical trials to evaluate new therapeutic approaches

Assembling patchy plasmonic nanoparticles with aggregation-dependent antibacterial activity

We realise an antibacterial nanomaterial based on the self-limited assembly of patchy plasmonic colloids, obtained by adsorption of lysozyme to gold nanoparticles. The possibility of selecting the size of the assemblies within several hundred nanometres allows for tuning their optical response in a wide range of frequencies from visible to near infrared. We also demonstrate an aggregation-dependent modulation of the catalytic activity, which results in an enhancement of the antibacterial performances for assemblies of the proper size. The gained overall control on structure, optical properties and biological activity of such nanomaterial paves the way for the development of novel antibacterial nanozymes with promising applications in treating multi drug resistant bacteria

Spatial patterns and temporal variability of drought in Western Iran

An analysis of drought in western Iran from 1966 to 2000 is presented using monthly precipitation data observed at 140 gauges uniformly distributed over the area. Drought conditions have been assessed by means of the Standardized Precipitation Index (SPI). To study the long-term drought variability the principal component analysis was applied to the SPI field computed on 12-month time scale. The analysis shows that applying an orthogonal rotation to the first two principal component patterns, two distinct sub-regions having different climatic variability may be identified. Results have been compared to those obtained for the largescale using re-analysis data suggesting a satisfactory agreement. Furthermore, the extension of the large-scale analysis to a longer period (1948–2007) shows that the spatial patterns and the associated time variability of drought are subjected to noticeable changes. Finally, the relationship between hydrological droughts in the two sub-regions and El Niño Southern Oscillation events has been investigated finding that there is not clear evidence for a link between the two phenomen