Diabetic retinopathy, oxidative stress and sirtuins: an in depth look in enzymatic patterns and new therapeutic horizons

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. DR represents the most common microvascular complication of diabetes, and its incidence is constantly rising. The complex interactions between inflammation, oxidative stress, and the production of free oxygen radicals caused by prolonged exposure to hyperglycemia determine the development of DR. Sirtuins (SIRTs) are a recently discovered class of 7 histone deacetylases involved in cellular senescence, regulation of cell cycle, metabolic pathways, and DNA repair. SIRTs participate in the progress of several pathologies such as cancer, neurodegenerative and metabolic diseases. In DR, sirtuins 1,3,5 and 6 play an important role as they regulate the activation of the inflammatory response, insulin sensibility, and both glycolysis and gluconeogenesis. A wide spectrum of direct and indirect activators of SIRTs pathways (e.g. antagomiR, resveratrol, or glycyrrhizin) is currently being developed to treat the inflammatory cascade occurring in DR. We focuse on the main metabolic and inflammatory pathways involving SIRTs and DR, as well as recent evidence on SIRTs activators that may be employed as novel therapeutic approaches to DR

Trapping and detrapping effects in high-quality chemical-vapor-deposition diamond films: Pulse shape analysis of diamond particle detectors

An analysis of the time evolution of the response of diamond particle detectors is carried out, using as a probe 5.5 MeV α particles impinging on high-quality diamond films grown by microwave chemical vapor deposition (CVD). Both the amplitude and the time evolution of the pulses are shown to change drastically when the detector is preirradiated with β particles (pumping), a slow component developing after pumping, indicating carriers trapping and releasing (detrapping). Pulse shapes obtained for positive and negative detector polarities are compared in both the as-grown and pumped states. The presence of at least two trapping centers for holes is necessary to explain the results, the shallower having an activation energy of about 0.3 eV. The effects of pumping are clarified, and the different role played by electrons and holes is evidenced. We modify a previous model for trapping-detrapping behavior originally applied to Si(Li) detectors to describe the more complex behavior of CVD diamond detectors, and develop a computer simulation based on it. The simulated pulse shapes agree very well with experiment with reasonable values of the physical parameters involved, making this technique helpful for studying and identifying defects which are responsible for limitation of the efficiency of CVD diamond particle detectors. Field-assisted detrapping seems to take place for fields of about 104 V/cm

Systematic study of the normal and pumped state of high efficiency diamond particle detectors grown by chemical vapor deposition

The efficiency and charge collection distance (CCD) of nuclear particle detectors based on high quality diamond films grown by chemical vapor deposition (CVD) have been systematically studied as a function of the methane content in the growth gas mixture and for varying film thickness. The effects of preirradiation with β particles (pumping) have been thoroughly studied. The results fully support a recently proposed model [Marinelli et al., Appl. Phys. Lett. 75, 3216 (1999)] discussing the role of in-grain defects and grain boundaries in determining the charge collection spectra of CVD diamond films both in the normal and in the pumped state. The model allows us to quantitatively explain the dependence of CCD and efficiency on film thickness, giving a microscopic picture of the effects of preirradiation with ionizing radiation in CVD diamond films. The highest average CCD obtained is 145 μm in a 160 μm thick detector (corresponding to about 50% average efficiency), while the maximum value (about 70% efficiency) is close to 370 μm. In addition, CCD is shown to be higher than film thickness and to monotonically increase with thickness, indicating margins for further improvements. © 2001 American Institute of Physics

Experimental determination of electron and hole mean drift distance: Application to chemical vapor deposition diamond

A study was performed on the experimental determination of electron and hole mean drift distance in chemical vapor deposition polycrystalline diamond. Air was used as an absorbing layer in order to change the energy of the impinging α particles. The results showed that the pumping process was much more effective on hole conduction

Relativistic three-body bound states and the reduction from four to three dimensions

Beginning with an effective field theory based upon meson exchange, the Bethe-Salpeter equation for the three-particle propagator (six-point function) is obtained. Using the one-boson-exchange form of the kernel, this equation is then analyzed using time-ordered perturbation theory, and a three-dimensional equation for the propagator is developed. The propagator consists of a pre-factor in which the relative energies are fixed by the initial state of the particles, an intermediate part in which only global propagation of the particles occurs, and a post-factor in which relative energies are fixed by the final state of the particles. The pre- and post-factors are necessary in order to account for the transition from states where particles are off their mass shell to states described by the global propagator with all of the particle energies on shell. The pole structure of the intermediate part of the propagator is used to determine the equation for the three-body bound state: a Schr{\"o}dinger-like relativistic equation with a single, global Green's function. The role of the pre- and post-factors in the relativistic dynamics is to incorporate the poles of the breakup channels in the initial and final states. The derivation of this equation by integrating over the relative times rather than via a constraint on relative momenta allows the inclusion of retardation and dynamical boost corrections without introducing unphysical singularities.Comment: REVTeX, 21 pages, 4 figures, epsf.st

Thermal and fast neutron detection in chemical vapor deposition single-crystal diamond detectors

Recently, a compact solid-state neutron detector capable of simultaneously detecting thermal and fast neutrons was proposed [M. Marinelli et al., Appl. Phys. Lett. 89, 143509 (2006)]. Its design is based on a p-type/intrinsic/metal layered structure obtained by Microwave Plasma Chemical Vapor Deposition (CVD) of homoepitaxial diamond followed by thermal evaporation of an Al contact and a ⁶LiF converting layer. Fast neutrons are directly detected in the CVD diamond bulk, since they have enough energy to produce the ¹²C(n, α)⁹Be reaction in diamond. Thermal neutrons are instead converted into charged particles in the ⁶LiF layer through the ⁶Li(n, α)T nuclear reaction. These charged particles are then detected in the diamond layer. The thickness of the ⁶LiF converting layer and the CVD diamond sensing layer affect the counting efficiency and energy resolution of the detector both for low- (thermal) and high-energy neutrons. An analysis is carried out on the dynamics of the ⁶Li(n, α)T and the ¹²C(n, α)⁹Be reactions products, and the distribution of the energy released inside the sensitive layer is calculated. The detector counting efficiency and energy resolution were accordingly derived as a function of the thickness of the ⁶LiF and CVD diamond layers, both for thermal and fast neutrons, thus allowing us to choose the optimum detector design for any particular application. Comparison with experimental results is also reported

Wild ungulates as sentinels of flaviviruses and tick-borne zoonotic pathogen circulation: an Italian perspective

Background: Vector-borne zoonotic diseases are a concerning issue in Europe. Lyme disease and tick-borne encephalitis virus (TBEV) have been reported in several countries with a large impact on public health; other emerging pathogens, such as Rickettsiales, and mosquito-borne flaviviruses have been increasingly reported. All these pathogens are linked to wild ungulates playing roles as tick feeders, spreaders, and sentinels for pathogen circulation. This study evaluated the prevalence of TBEV, Borrelia burgdorferi sensu lato, Rickettsia spp., Ehrlichia spp., and Coxiella spp. by biomolecular screening of blood samples and ticks collected from wild ungulates. Ungulates were also screened by ELISA and virus neutralization tests for flaviviral antibody detection. Results: A total of 274 blood samples were collected from several wild ungulate species, as well as 406 Ixodes ricinus, which were feeding on them. Blood samples tested positive for B. burgdorferi s.l. (1.1%; 0-2.3%) and Rickettsia spp. (1.1%; 0-2.3%) and showed an overall flaviviral seroprevalence of 30.6% (22.1-39.2%): 26.1% (17.9-34.3%) for TBEV, 3.6% (0.1-7.1%) for Usutu virus and 0.9% (0-2.7%) for West Nile virus. Ticks were pooled when possible and yielded 331 tick samples that tested positive for B. burgdorferi s.l. (8.8%; 5.8-11.8%), Rickettsia spp. (26.6%; 21.8-31.2%) and Neoehrlichia mikurensis (1.2%; 0-2.4%). TBEV and Coxiella spp. were not detected in either blood or tick samples. Conclusions: This research highlighted a high prevalence of several tick-borne zoonotic pathogens and high seroprevalence for flaviviruses in both hilly and alpine areas. For the first time, an alpine chamois tested positive for anti-TBEV antibodies. Ungulate species are of particular interest due to their sentinel role in flavivirus circulation and their indirect role in tick-borne diseases and maintenance as Ixodes feeders and spreaders

Characterization of damage induced by heavy neutron irradiation on multilayered 6LiF-single crystal chemical vapor deposition diamond detectors

High performance neutron detectors sensitive to both thermal and fast neutrons are of great interest to monitor the high neutron flux produced, e.g., by fission and fusion reactors. An obvious requirement for such an application is neutron irradiation hardness. This is why diamond based neutron detectors are currently under test in some of these facilities. In this paper the damaging effects induced in chemical vapor deposition (CVD) diamond based detectors by a neutron fluence of ~2 × 10¹⁶ neutrons/cm² have been studied and significant changes in spectroscopic, electrical, and optical properties have been observed. The detectors are fabricated using high quality synthetic CVD single crystal diamond using the p-type/intrinsic/Schottky metal/⁶LiF layered structure recently proposed by Marinelli et al [Appl. Phys. Lett. 89, 143509 (2006)], which allows simultaneous detection of thermal and fast neutrons. Neutron radiation hardness up to at least 2 × 10¹⁴ n/cm² fast (14 MeV) neutron fluence has been confirmed so far [see Pillon et al, Fusion Eng. Des. 82, 1174 (2007)]. However, at the much higher neutron fluence of ~2 × 10¹⁶ neutrons/cm² damage is observed. The detector response to 5.5 MeV ²⁴¹Am α-particles still shows a well resolved α-peak, thus confirming the good radiation hardness of the device but a remarkable degradation and a significant instability with time of charge collection efficiency and energy resolution arise. Symmetric, nearly Ohmic I-V (current-voltage) characteristics have been recorded from the metal/intrinsic/p-doped diamond layered structure, which before neutron irradiation acted as a Schottky barrier diode with a strong rectifying behavior. The nature and the distribution of the radiation induced damage have been deeply examined by means of cathodoluminescence spectroscopy. A more heavily damaged area into the intrinsic diamond at the same position and with the same extension of the ⁶LiF layer has been found, the increased damage being ascribed to the highly ionizing particles produced in the ⁶LiF layer by thermal neutrons through the nuclear reaction ⁶Li(n, α)T