Semi-classical signal analysis

This study introduces a new signal analysis method, based on a semi-classical approach. The main idea in this method is to interpret a pulse-shaped signal as a potential of a Schrödinger operator and then to use the discrete spectrum of this operator for the analysis of the signal. We present some numerical examples and the first results obtained with this method on the analysis of arterial blood pressure waveforms.     

The beta-cell in type 1 diabetes: What have we learned from proteomic studies?

Pancreatic beta-cells have a crucial role in the regulation of blood glucose homeostasis by the production and secretion of insulin. In type 1 diabetes (T1D), an autoimmune reaction against the beta-cells together with the presence of inflammatory cytokines and ROS in the islets leads to beta-cell dysfunction and death. This review gives an overview of proteomic studies that lead to better understanding of beta-cell functioning in T1D. Protein profiling of isolated islets and beta-cell lines in health and T1D contributed to the unraveling of pathways involved in cytokine-induced cell death. In addition, by studying the serological proteome of T1D patients, new biomarkers and beta-cell autoantigens were discovered, which may improve screening tests and follow-up of T1D development. Interestingly, an important role for PTMs was demonstrated in the generation of beta-cell autoantigens. To conclude, proteomic techniques are of indispensable value to improve the knowledge on beta-cell function in T1D and the search toward therapeutic targets.     

Cyclooxygenase-2 unlike cyclooxygenase-1 is highly expressed in ovine embryos during the implantation period

In this study we investigated expression of the two isoforms of the prostaglandin-forming enzyme, cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2), in sheep embryos. Using Western blot and immunohistochemical analyses, we demonstrated that Cox-2 was highly expressed in embryos from Day 8 to Day 17 of development whereas Cox-1 was undetectable during this time. The expression of Cox-2 was developmentally regulated. It was maximal between Days 14 and 16. There was a 30-fold increase in Cox-2 content per protein extract between Day 10 and Day 14, corresponding to a 50,000-fold increase in the whole embryo. The expression of Cox-2 declined after Day 16 to become undetectable by Day 25 of pregnancy. Cox-2 was localized in the trophoblastic cells and was not detected in the inner cell mass. The [3H]arachidonic acid metabolites synthesized by Cox-2-rich conceptuses were analyzed by HPLC after short-term embryo culture. Day 14 conceptuses released mainly cyclooxygenase metabolites and to a lesser extent lipoxygenase derivatives. Cyclooxygenase products were 6-keto-prostaglandin (PGF)1alpha 18.2% (+/- 4.2), thromboxane-B2 22.51% (+/- 15.9), PGF2alpha 21% (+/- 11), PGE2 14.5% (+/- 7.4), and PGD2 2.7% (+/- 2.6). Taken together, these results suggest an important role for the Cox-2-dependent cyclooxygenase metabolites during embryo development.     

Study of silicon photomultipliers fast amplifier and thermoregulation

The silicon photomultipliers (SiPM) are adopted in various physical applications, from medical physics to astrophysics, for their advantages in terms of cost and weight with respect to traditional photo detectors. Their low bias voltage supply (about 30 V), hardiness and resistance to magnetic field are ideal characteristics for space application. In the frame of INFN-Irst collaboration, some of them have been developed and produced at FBK (Trento-Italy), and have been characterized in the INFN laboratories of Bologna (DaSiPM2 collaboration).The SiPM can be used in conjunction with fibres and counters in high energy physics experiments. To exploit the SiPM time resolution, a fast amplifier has been studied. The SiPM gain depends critically on temperature and a thermal stabilization is also necessary. The use of a thermoelectric cooler module based on a Peltier cell has been investigated, and the results are shown.     

A monoclonal antibody to the ligand-binding domain of the neurokinin 1 receptor (NK1-R) for the neuropeptide substance P

For PCR-based genotyping using polymorphic microsatellite markers, DNA from decomposed postmortem human tissues was fractionated into six groups according to molecular size. The minimum required amounts of this degraded DNA, for detecting alleles at five microsatellite loci (ACTBP2, CMAG, HUMTH01, CYP19, and LPL) and one minisatellite locus (MCT118) were investigated respectively. The allele patterns were detected by electrophoresis of the PCR products on a 6%-denaturing polyacrylamide gel following silver staining. The detection of alleles for the loci with large allele size required more template DNA with higher molecular size than for that with small allele size. Amounts from 0.3 ng to 5 ng were needed for allele detection on genomic DNA from fresh blood. When the decomposed DNA mixture was used as the template, approximately ten times the amount of genomic DNA was required to detect alleles at the three loci of LPL, CYP19 and HUMTH01, while 24 to 67 times was required for the loci, CMAG, ACTBP2 and MCT118. It was demonstrated that a minimum molecular, size and amount of template DNA was needed for amplifying alleles of the six loci, and degraded DNA less than minimum size in the samples would prevent the detection of the loci which have large allele size.     

Rheological characterisation of salad-dressing-type emulsions stabilised by egg yolk/sucrose distearate blends

The overall objective of this work was to fully characterise the rheological behaviour of oil/water emulsions stabilised by egg yolk and a sucrose ester of intermediate hydrophilic-lipophilic balance. The influence of the egg yolk/sucrose ester weight ratio in the emulsifier blend was studied by keeping the total amount of emulsifier constant. With this aim, steady state and transient flow tests, oscillatory measurements within the linear viscoelasticity regime and stress relaxation tests were carried out. Rheological tests were complemented with droplet size measurements. The results demonstrate that the rheological response and droplet size of the emulsions studied clearly depend on the weight ratio of emulsifiers in the binary blends. Steady-state and transient viscosities, as well as the dynamic functions, significantly increase with sucrose distearate concentration in the emulsifier blend. However, the evolution of other rheological parameters related to shear-induced structural breakdown, such as the critical strain for the onset of the non-linear viscoelastic behaviour, the relative deviation of the Cox-Merz rule, the time corresponding to the stress overshoot in transient tests or the damping function indicates a more developed and resistant structural network at higher egg yolk concentrations in the emulsifier blend. These results were discussed on the basis of a gel-like continuous phase formed by the sucrose ester and the highly flocculated state favoured by egg yolk.     

Nebulized Gadolinium‐Based Nanoparticles: A Theranostic Approach for Lung Tumor Imaging and Radiosensitization

Lung cancer is the most common and most fatal cancer worldwide. Thus, improving early diagnosis and therapy is necessary. Previously, gadolinium‐based ultra‐small rigid platforms (USRPs) were developed to serve as multimodal imaging probes and as radiosensitizing agents. In addition, it was demonstrated that USRPs can be detected in the lungs using ultrashort echo‐time magnetic resonance imaging (UTE‐MRI) and fluorescence imaging after intrapulmonary administration in healthy animals. The goal of the present study is to evaluate their theranostic properties in mice with bioluminescent orthotopic lung cancer, after intrapulmonary nebulization or conventional intravenous administration. It is found that lung tumors can be detected non‐invasively using fluorescence tomography or UTE‐MRI after nebulization of USRPs, and this is confirmed by histological analysis of the lung sections. The deposition of USRPs around the tumor nodules is sufficient to generate a radiosensitizing effect when the mice are subjected to a single dose of 10 Gy conventional radiation one day after inhalation (mean survival time of 112 days versus 77 days for irradiated mice without USRPs treatment). No apparent systemic toxicity or induction of inflammation is observed. These results demonstrate the theranostic properties of USRPs for the multimodal detection of lung tumors and improved radiotherapy after nebulization.     

Ultrasmall Nanoplatforms as Calcium‐Responsive Contrast Agents for Magnetic Resonance Imaging

The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle‐based, calcium‐responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA‐USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA‐USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca²⁺. Cell viability is probed with the MTT assay using HEK‐293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA‐USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl₂ is also administrated. Laser‐induced breakdown spectroscopy experiments confirm accumulation of SCA‐USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium‐sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium‐dependent physiological and pathological processes in a dynamic manner.     

Fibroblast growth factor-2 has opposite effects on human breast cancer MCF-7 cell growth depending on the activation level of the mitogen-activated protein kinase pathway

In human breast cancer MCF-7 and MCF-7ras cells, we demonstrated that whereas insulin had a mitogenic effect on both cell lines, fibroblast growth factor-2 (FGF-2) had opposite effects, stimulating MCF-7 and inhibiting MCF-7ras cell proliferation. The inhibitory signal induced by FGF-2 was related to sustained mitogen-activated protein kinase (MAPK) activation in MCF-7ras cells, while transient MAPK activation was associated with MCF-7 cell proliferation. FGF-2 was further used in combination with insulin or cAMP. In MCF-7 cells, insulin and cAMP reversed the mitogenic effect of FGF-2. In MCF-7ras cells, insulin did not modify the inhibitory effect of FGF-2, but cAMP markedly enhanced it. These effects were also associated with an increased level and duration of MAPK activation. PD98056 abolished the effect of FGF-2 on DNA synthesis in both cell lines, demonstrating that the dual effect of FGF-2 on cell proliferation is dependent on the activity of the extracellular-signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway.     

Nebivolol: comparison of the effects of dl-nebivolol, d-nebivolol, l-nebivolol, atenolol, and placebo on exercise-induced increases in heart rate and systolic blood pressure

Congenital subluxation of the peroneal tendons is an uncommon, but not rare condition. In almost all cases, it will spontaneously resolve without requiring any treatment. Presented is a case report of the condition affecting the patient bilaterally. The subluxation did not resolve and the patient was subsequently treated with a modification of the Kelly procedure.