Stringent bounds on HWWHWW and HZZHZZ anomalous couplings with quantum tomography at the LHC

Quantum tomography provides the full reconstruction of the density matrix of a state. We use it to study the Higgs boson decay into weak gauge bosons. Anomalous couplings beyond the Standard Model can be constrained by means of observables easily defined in terms of entries of the polarization density matrix. We describe a strategy based on two observables that together provide the most stringent limits. One of these observables is linked to entanglement between the polarizations of the two gauge bosons, the other to CP-odd combinations of one momentum and two polarizations. We find that this strategy could offer, already with the available LHC data, an improvement by a factor of 5 to one order of magnitude with respect to the best current bounds.Comment: 13 pages, 3 figures. arXiv admin note: text overlap with arXiv:2302.0068

Polymer-coated superparamagnetic iron oxide nanoparticles as T-2 contrast agent for MRI and their uptake in liver

Aim: To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T-2 magnetic resonance contrast agent and their uptake and toxicity in liver. Materials & methods: Mice were intravenously injected with bioferrofluids and Endorem (R). The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques. Results: Bioferrofluids are a good T-2 contrast agent with a higher r(2)/r(1) ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection. Conclusion: Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection. Lay abstract: Several superparamagnetic iron oxide nanoparticles (SPIONs) preparations have been approved by US FDA for clinical use as MRI contrast agents. In recent years, we have been developing a synthetic multifunctional platform for SPIONs based on the use of polymers. In this report, we explored the diagnostic potential of these nanoparticles (herein called bioferrofluids) as an MRI contrast agent and their uptake in liver, without neglecting their toxicological effects. Results show that our bioferrofluids are a good T-2 contrast agent without any observed toxicity in liver

PSMA PET/CT in Castration-Resistant Prostate Cancer: Myth or Reality?

Background: prostate-specific membrane antigen (PSMA) ligand PET has been recently incorporated into international guidelines for several different indications in prostate cancer (PCa) patients. However, there are still some open questions regarding the role of PSMA ligand PET in castration-resistant prostate cancer (CRPC). The aim of this work is to assess the clinical value of PSMA ligand PET/CT in patients with CRPC. Results: PSMA ligand PET has demonstrated higher detection rates in comparison to conventional imaging and allows for a significant reduction in the number of M0 CRPC patients. However, its real impact on patients’ prognosis is still an open question. Moreover, in CRPC patients, PSMA ligand PET presents some sensitivity and specificity limitations. Due to its heterogeneity, CRPC may present a mosaic of neoplastic clones, some of which could be PSMA−/FDG+, or vice versa. Likewise, unspecific bone uptake (UBU) and second primary neoplasms (SNPs) overexpressing PSMA in the neoangiogenic vessels represent potential specificity issues. Integrated multi-tracer imaging (PSMA ligand and [18F]FDG PET) together with a multidisciplinary discussion could allow for reaching the most accurate evaluation of each patient from a precision medicine point of view

An in vivo study of quantum dots tissue accumulation

Nanotechnology represents a new frontier for the science progress and there are great expectations in relation to diagnostic and therapeutic envelopes [1]. Living organisms are built of cells that are typically 10 \u3bcm across. However, the cell parts are much smaller and are in the sub-micron size domain, for example a red blood cell is approximately 7,000 nm wide. Even smaller are the proteins with a typical size of just 5 nm, which is comparable with the dimensions of smallest manmade nanoparticles. This simple size comparison gives an idea of using nanoparticles as very small probes that would allow us to spy at the cellular machinery without introducing too much interference. Understanding of biological processes on the nanoscale level is a strong driving force behind development of nanotechnologyOur current knowledge of the toxicology of nanoparticles in vivo is poor [2] but suggests that nanoparticles may able to have adverse effects at their portal of entry , for example, the lungs, but that some nanoparticles may also escape the normal defences and translocate from their portal of entry to have diverse effects in other target organs [3].There is no cut-off below witch particles suddenly become harmful, in the lung at least. This is because harmful particles have their effects as a consequence of two factors that act together to determine their potential to cause harm: their large surface area, and the reactivity or intrinsic toxicity of the surface. It is self evident that the smaller particles are, the more surface area they have per unit mass; therefore any intrinsic toxicity of the particles surface will be emphasised. Some of the most complex nanoparticles are likely to be produced for therapeutic purposes, furthermore nanoparticles binding to protein may result in a series of consequences not expected to occur when proteins bind to large particles. Very small particles may be not detected by the normal phagocytic defences, allowing them to gain access to the blood or nervous system [4]. Very small particles are smaller than some molecules and could act like haptens to modify protein structures, either altering their function or rendering them antigenic, raising the potential for autoimmune effects.Tracers that we have used are nanoparticles with optical properties, fluorescent semiconductors, that absorb photons of light and re-emit photons at a different wavelength They are known as quantum dots (QDs), nanocrystals that are nanometres-scale (10-20nm, roughly protein-sized) atom clusters, containing from a few hundred to a few thousand atoms of a semiconductor material (cadmium mixed with selenium), which has been coated with an additional semiconductor shell (zinc sulfide) to improve the optical properties of the material. These nanoparticles fluoresce in a different way than do traditional fluorophores, they exhibit some important differences as compared to organic fluorescent dyes and naturally fluorescent proteins: they have an extinction coefficient 10-50 times bigger than them. These nanoparticles projected around their optical properties: stable , bright and photo-stable fluorescence, observed and measured for hours, and that persists also into isolated tissues. Nanoparticles like QDs, could be targeted and not targeted and provided several unique features and capabilities[5, 6]: the size-effect does the QDs cancer biomarkers and there is the possibility to functionalize their surface area with a several numbers of functional groups that can be linked with multiple diagnostic (e.g. radio-isotopic or magnetic) and therapeutic agents. The aim of the study is to monitor nanoparticles behaviour into blood system: kinetic, T1/2, bio distribution, and tissues accumulation. We would extrapolate from optics parameters physiological ones, in specific districts so as liver and lungs that are the most probably targets of toxicity

Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal development at the periphery of carcinomas

Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed during 2 weeks of daily administration of an inhibitor of tyrosine kinase receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a hyper-enhancing rim, not observed in untreated tumours. To account for tissue heterogeneity in the quantitative analysis, we segmented tumours into three subunits automatically identified by cluster analysis of the enhancement curves using a k-means algorithm. Transendothelial permeability (Kps) and fractional plasma volume (fPV) were calculated in each subunit. An avascular and necrotic region, an intermediate zone and a well-vascularised periphery were reliably identified. During untreated tumour growth, the identified sub-regions did not substantially change their enhancement pattern. Treatment with SU6668 induced major changes at tumour periphery where a significant increase of Kps and fPV was observed with respect to control tumours. Histology revealed a sub-capsular layer composed of hyper-dense viable tumour cells in the periphery of untreated tumours. The rim of viable neoplastic cells was reduced in treated tumours, and replaced by loose connective tissue characterised by numerous vessels, which explains the observed hyper-enhancement. The present data show a peripheral abnormal development of cancer-associated stroma, indicative of an adaptive response to anti-angiogenic treatment

Bioluminescence imaging in brain tumor: a powerful tool

Glioblastoma represents the most malignant and lethal among brain tumours because of its highly infiltration capacity and invasion into the normal brain that account for its resistance to treatments (chemotherapy and radiotherapy). Recent advance and development of technologies to non-invasively image brain tumour growth in living animals can open an opportunity to monitor directly the efficacy of the treatment on tumour development. In vivo bioluminescence imaging is based on light-emitting enzymes, luciferases, which require specific substrates for light production. When linked to a specific biological process/pathway in an animal model of human disease, the enzyme-substrate interactions become biological indicators that can be studied. In order to explore and compare different imaging modalities (MRI and bioluminescence imaging) we have validated the use of bioluminescence imaging to monitor glioblastoma progression in vivo. The human glioma cell line (DBTRG-05MG) derived from an adult patient with glioblastoma multiforme who had been treated with local brain irradiation and multidrug chemotherapy has been used for the experiment. The DBTRG-05MG cell line was stably transfected with TCF-luciferase and orthotopic implantated onto immunodeficient mice. Bioluminescence technology was used to follow tumour growth in parallel with classical MRI on the same animals

Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: a new method to obtain labeled exosomes

Purpose: Recent findings indicate that the beneficial effects of adipose stem cells (ASCs), reported in several neurodegenerative experimental models, could be due to their paracrine activity mediated by the release of exosomes. The aim of this study was the development and validation of an innovative exosome-labeling protocol that allows to visualize them with magnetic resonance imaging (MRI).Materials and methods: At first, ASCs were labeled using ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, 4\u20136 nm), and optimal parameters to label ASCs in terms of cell viability, labeling efficiency, iron content, and magnetic resonance (MR) image contrast were investigated. Exosomes were then isolated from labeled ASCs using a standard isolation protocol. The efficiency of exosome labeling was assessed by acquiring MR images in vitro and in vivo as well as by determining their iron content. Transmission electron microscopy images and histological analysis were performed to validate the results obtained.Results: By using optimized experimental parameters for ASC labeling (200 \ub5g Fe/mL of USPIO and 72 hours of incubation), it was possible to label 100% of the cells, while their viability remained comparable to unlabeled cells; the detection limit of MR images was of 102 and 2.5 7103 ASCs in vitro and in vivo, respectively. Exosomes isolated from previously labeled ASCs retain nanoparticles, as demonstrated by transmission electron microscopy images. The detection limit by MRI was 3 \ub5g and 5 \ub5g of exosomes in vitro and in vivo, respectively.Conclusion: We report a new approach for labeling of exosomes by USPIO that allows detection by MRI while preserving their morphology and physiological characteristics