Experimental determination of the frequency and field dependence of Specific Loss Power in Magnetic Fluid Hyperthermia

Magnetic nanoparticles are promising systems for biomedical applications and in particular for Magnetic Fluid Hyperthermia, a promising therapy that utilizes the heat released by such systems to damage tumor cells. We present an experimental study of the physical properties that influences the capability of heat release, i.e. the Specific Loss Power, SLP, of three biocompatible ferrofluid samples having a magnetic core of maghemite with different core diameter d= 10.2, 14.6 and 19.7 nm. The SLP was measured as a function of frequency f and intensity of the applied alternating magnetic field H, and it turned out to depend on the core diameter, as expected. The results allowed us to highlight experimentally that the physical mechanism responsible for the heating is size-dependent and to establish, at applied constant frequency, the phenomenological functional relationship SLP=cH^x, with 2<x<3 for all samples. The x-value depends on sample size and field frequency/ intensity, here chosen in the typical range of operating magnetic hyperthermia devices. For the smallest sample, the effective relaxation time Teff=19.5 ns obtained from SLP data is in agreement with the value estimated from magnetization data, thus confirming the validity of the Linear Response Theory model for this system at properly chosen field intensity and frequency

Relative influence of the adeno-associated virus (AAV) type 2 p5 element for recombinant AAV vector site-specific integration.

The p5 promoter region of the adeno-associated virus type 2 (AAV-2) rep gene has been described as essential for Rep-mediated site-specific integration (RMSSI) of plasmid sequences in human chromosome 19. We report here that insertion of a full-length or minimal p5 element between the viral inverted terminal repeats does not significantly increase RMSSI of a recombinant AAV (rAAV) vector after infection of growth-arrested or proliferating human cells. This result suggests that the p5 element may not improve RMSSI of rAAV vectors in vivo

Detection of pollutant sources in the atmosphere with Lidar/Dial techniques: Results of an experimental campaign in the south of Italy

In the last years, surveying large regions of the atmosphere in an automatic way, for early detection of pollutant sources in urban and industrial areas, has become a strategic objective of various public health organizations. The Lidar/Dial technique has become a well-established laser remote sensing method for atmosphere monitoring. It is often used to probe almost any level of the atmosphere and to acquire information necessary to validate theoretical models about different topics of atmospheric physics. It can also be deployed for environment surveying by monitoring particles, aerosols and molecules. For these reasons, an experimental campaign for evaluating the performances of a Lidar/Dial system in detecting pollutants (particulate and/or chemical compounds) has been carried out in an industrial area in the south of Italy. In this work, a homemade Lidar/Dial system (developed and built by the authors) and the results of the experimental campaign will be presented and discussed. © 2014 AEIT

Procedures of sensors deployment methodology on physical supports/platforms

The aim of task 2.3 is to define specific platform characteristics and identify deployment difficulties in order to determine the adequacy of sensors within specific platforms. In order to obtain the necessary information, two online questionnaires were realized. One questionnaire was created for sensor developers and one for those partners that will test the sensors at sea. The seven developers in COMMON SENSE have provided information on seven sensors: two for underwater noise – CEFAS and IOPAN; two for microplastics – IDRONAUT and LEITAT; one for an innovative piro and piezo resistive polymeric temperature and pressure – CSIC; one for heavy metal – CSIC; one for eutrophication sensor – DCU. Outside the scope of the questionnaire, FTM has proposed three sensors of which two for oil spill and one for heavy metals, realized in the framework of a previous EU project but that can be improved and tested with several platforms. This information is anyway incomplete because in most cases for the novel sensors which will be developed over the course of COMMON SENSE, the sensors cannot be clearly designed yet as the project only started a few months ago - and, consequently, technical characteristics cannot actually be perfectly defined. This produces some lag in the acquired information that will be solved in the near future. In the other questionnaire, partners-testers have provided information on eleven platforms. Outside the questionnaire, IOPAN has described two more platforms, one of which is a motorboat not previously listed in the DoW, and they have informed us that the oceanographic buoy in Gdansk Bay is not actually available. This is valid also for platforms from other partners where there were only preliminary contacts like for example for Aqualog and OBSEA Underwater observatory. In the following months, new information will be provided and questionnaires information updated. Then important characteristics have to be considered such as maintenance, energy autonomy, data transfer/storage and dimension of the sensors that are actually missing. Further updates of this report are therefore necessary in order to individuate the most suitable platforms to test each kind of sensor and then used at the end of 2014 when WP9 (Testing activities) will start. Objectives and rationale The objective of deliverable 2.2 is the definition of the characteristics and procedures of sensors deployment methodology on physical supports/platforms, possible needs and characteristics of the available platform. This is preparatory for the activities in other WPs and tasks: - for task 2.2 (New generation technologies), that will provide cost-effective sensors for large scale production through Deliverable 2.1 [month 10]; - for task 2.5 (Monitoring strategy) where sensitivity and stress tests of new sensors will be designed in order to establish confidence limits under different situations and certify the performance of the new instruments [Deliverable 2.5 at month 16]. - for WP9 (Field testing) starting at month 12 (October 2014) when the deployment of new sensors will be drawn and then realized

Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression

Lin28 is an evolutionary conserved RNA-binding protein that plays important roles during embryonic development and tumorigenesis. It regulates gene expression through two different post-transcriptional mechanisms. The first one is based on the regulation of miRNA biogenesis, in particular that of the let-7 family, whose expression is suppressed by Lin28. Thus, loss of Lin28 leads to the upregulation of mRNAs that are targets of let-7 species. The second mechanism is based on the direct interaction of Lin28 with a large number of mRNAs, which results in the regulation of their translation. This second mechanism remains poorly understood. To address this issue, we purified high molecular weight complexes containing Lin28a in mouse embryonic stem cells (ESCs). Numerous proteins, co-purified with Lin28a, were identified by proteomic procedures and tested for their possible role in Lin28a-dependent regulation of the mRNA encoding DNA methyltransferase 3a (Dnmt3a). The results show that Lin28a activity is dependent on many proteins, including three helicases and four RNA-binding proteins. The suppression of four of these proteins, namely Ddx3x, Hnrnph1, Hnrnpu or Syncrip, interferes with the binding of Lin28a to the Dnmt3a mRNA, thus suggesting that they are part of an oligomeric ribonucleoprotein complex that is necessary for Lin28a activity

Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signalling pathway

Aims: Homozygosity for a four-missense single-nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this longevity-associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy. Methods and results: Compared with age-matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV-BPIFB4 gene therapy using an adeno-associated viral vector serotype 9 (AAV9). In contrast, AAV9 wild-type-BPIFB4 exerted no benefit. Interestingly, LAV-BPIFB4-treated mice showed increased SDF-1 levels in peripheral blood and myocardium and up-regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF-1 up-regulation was instrumental to LAV-BPIFB4-induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF-1 CXCR4 receptor. Conclusions: In mice with type-2 diabetes, LAV-BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes-induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease

BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice

Long-living individuals (LLIs) escape age-related cardiovascular complications until the very last stage of life. Previous studies have shown that a Longevity-Associated Variant (LAV) of the BPI Fold Containing Family B Member 4 (BPIFB4) gene correlates with an extraordinarily prolonged life span. Moreover, delivery of the LAV-BPIFB4 gene exerted therapeutic action in murine models of atherosclerosis, limb ischemia, diabetic cardiomyopathy, and aging. We hypothesize that downregulation of BPIFB4 expression marks the severity of coronary artery disease (CAD) in human subjects, and supplementation of the LAV-BPIFB4 protects the heart from ischemia. In an elderly cohort with acute myocardial infarction (MI), patients with three-vessel CAD were characterized by lower levels of the natural logarithm (Ln) of peripheral blood BPIFB4 (p = 0.0077). The inverse association between Ln BPIFB4 and three-vessel CAD was confirmed by logistic regression adjusting for confounders (Odds Ratio = 0.81, p = 0.0054). Moreover, in infarcted mice, a single administration of LAV-BPIFB4 rescued cardiac function and vascularization. In vitro studies showed that LAV-BPIFB4 protein supplementation exerted chronotropic and inotropic actions on induced pluripotent stem cell (iPSC)-derived cardiomyocytes. In addition, LAV-BPIFB4 inhibited the pro-fibrotic phenotype in human cardiac fibroblasts. These findings provide a strong rationale and proof of concept evidence for treating CAD with the longevity BPIFB4 gene/protein

The SURF (Italian observational study for renal insufficiency evaluation in liver transplant recipients): A post-hoc between-sex analysis

Background: Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage. Methods: All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) &lt; 60 ml/min/1.73m2 at inclusion and follow-up visit. Results: Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR &lt; 60 mL/min/1.73 m2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O'Riordan eGFR levels were observed at time of transplant and study initial visit (p = 0.0005 and 0.0299 respectively), but not at follow-up. Conclusions: Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth

System Test of the ATLAS Muon Spectrometer in the H8 Beam at the CERN SPS

An extensive system test of the ATLAS muon spectrometer has been performed in the H8 beam line at the CERN SPS during the last four years. This spectrometer will use pressurized Monitored Drift Tube (MDT) chambers and Cathode Strip Chambers (CSC) for precision tracking, Resistive Plate Chambers (RPCs) for triggering in the barrel and Thin Gap Chambers (TGCs) for triggering in the end-cap region. The test set-up emulates one projective tower of the barrel (six MDT chambers and six RPCs) and one end-cap octant (six MDT chambers, A CSC and three TGCs). The barrel and end-cap stands have also been equipped with optical alignment systems, aiming at a relative positioning of the precision chambers in each tower to 30-40 micrometers. In addition to the performance of the detectors and the alignment scheme, many other systems aspects of the ATLAS muon spectrometer have been tested and validated with this setup, such as the mechanical detector integration and installation, the detector control system, the data acquisition, high level trigger software and off-line event reconstruction. Measurements with muon energies ranging from 20 to 300 GeV have allowed measuring the trigger and tracking performance of this set-up, in a configuration very similar to the final spectrometer. A special bunched muon beam with 25 ns bunch spacing, emulating the LHC bunch structure, has been used to study the timing resolution and bunch identification performance of the trigger chambers. The ATLAS first-level trigger chain has been operated with muon trigger signals for the first time

Review of existing and operable observing systems and sensors

Deliverable 1.4 is aimed at identification of existing and operable observing systems and sensors which are relevant to COMMON SENSE objectives. Report aggregates information on existing observing initiatives, programmes, systems, platforms and sensors. The Report includes: • inventory of previous and current EU funded projects. Some of the them, even if started before 2007, were aimed at activities which are relevant or in line with those stemming from MSFD in 2008. The ‘granulation’ of the contents and objectives of the projects varies from sensors development through observation methodologies to monitoring strategies, • inventory of research infrastructure in Europe. It starts from an attempt to define of Marine Research Infrastructure, as there is not a single definition of Research Infrastructure (RI) or of Marine Research Infrastructure (MRI), and there are different ways to categorise them. The chapter gives the categorization of the MRI, together with detailed description and examples of MRI – research platforms, marine data systems, research sites and laboratories with respect of four MSFD descriptors relevant to COMMON SENSE project, • two chapters on Research Programs and Infrastructure Networks; the pan-European initiatives aimed at cooperation and efficient use of infrastructural resources for marine observation and monitoring and data exchange are analysed. The detailed description of observing sensors and system are presented as well as frameworks for cooperation, • information on platforms (research vessels) available to the Project for testing developed sensors and systems. Platforms are available and operating in all three regions of interest to the project (Mediterranean, North Sea, Baltic), • annexed detailed description of two world-wide observation networks and systems. These systems are excellent examples of added value offered by integrated systems of ocean observation (from data to knowledge) and how they work in practice. Report concludes that it is seen a shortage of new classes of sensors to fulfil the emerging monitoring needs. Sensors proposed to be developed by COMMON SENSE project shall answer to the needs stemmed from introduction of MSFD and GES descriptors