There is growing support that environmental influences and individual genetic susceptibility may increase the incidence and accelerate the onset of Alzheimer’s disease (AD). Epigenetic mechanisms ...encompass a complex regulatory network of modifications with considerable impact on health and disease risk. Abnormal epigenetic regulation is a hallmark in many pathological conditions including AD. It is well recognized that numerous bioactive dietary components mediate epigenetic modifications associated with the pathophysiology of several diseases. Although the influences of dietary factors on epigenetic regulation have been extensively investigated, only few studies have explored the effects of specific food components in regulating epigenetic patterns during neurodegeneration and AD. Epigenetic nutritional research has substantial potential for AD and may represent a window of opportunity to complement other interventions. Here, we provide a brief overview of the main mechanisms involved in AD, some of which may be epigenetically modulated by bioactive food.
Abstract
The experimental fusion reactor ITER will feature two (or three) heating neutral beam injectors (NBI) capable of delivering 33(or 50) MW of power into the plasma. A NBI consists of a plasma ...source for production of negative ions (extracted negative ion current up to 329 A/m
2
in H and 285 A/m
2
in D) then accelerated up to 1 MeV for one hour. The negative ion beam is neutralized, and the residual ions are electrostatically removed before injection. The beamline was designed for a beam divergence between 3 and 7 mrad.
The ion source in ITER NBIs relies on RF-driven, Inductively-Coupled Plasmas (ICP), based on the prototypes developed at IPP Garching; RF-driven negative-ion beam sources have never been employed in fusion devices up to now. The recent results of SPIDER, the full size ITER NBI ion source operating at NBTF in Consorzio RFX, Padova, measure a beamlet divergence minimum of 12mrad and highlighted beam spatial non-uniformity. SPIDER results confirmed the experimental divergence found in smaller prototype sources, which is larger compared to filament-arc ion sources. Although prototype experiments have shown that the extracted current requirement can be achieved with minor design improvements, the beamlet divergence is expected to marginally achieve the design value of 7 mrad, which in multi-grid long accelerators results in unexpected heat loads over the accelerator grids. A contributor to the beam divergence is the energy/temperature of the extracted negative ions, so it is believed that plasma differences between the two source types play a role. Research is focused on the plasma parameters in the ion source.
One RF driver, identical to the ones used in SPIDER, installed in a relatively small-scale experimental set-up, inherently more flexible than large devices, is starting operations devoted to the investigation of the properties of RF-generated plasmas, so as to contribute to the assessment of negative ion precursors, and of their relationship with the plasma parameters, particularly when enhancing plasma confinement. The scientific questions, that have arisen from the preliminary results of SPIDER, guided the design of the test stand, which are described in this contribution, together with the diagnostic systems and related simulation tools. The test stand, which shares with the larger experiment all the geometrical features and constraints, will allow technological developments and optimized engineering solutions related to the ICP design for the ITER NBIs.
The Acceleration Grid Power Supply Conversion System (AGPS-CS) of the MITICA Neutral Beam Injector has been installed between late 2017 - early 2018 and commissioned in the first half of 2018. This ...paper is focused on the installation and commissioning activities, with emphasis on the integration issues. The results of the site and acceptance tests are presented, proving the capability of the system to deliver the specified performance.
Since the discovery of p53 as "guardian of the genome", a large number of efforts have been put in place in order to find molecular strategies aiming to restore p53 wild-type functions, particularly ...in the light of the fact that its pathway results ineffective in most tumors even though they have non-mutated p53. In this context, pediatric cancers, that are mostly p53 wild-type at the time of diagnosis, represent an ideal target for such therapeutic approach. Within the several mechanisms and proteins ruling p53 activity, the murine double minute 2 (MDM2) is its crucial negative regulator, frequently found overexpressed in p53-wild-type tumors. The development of new technologies such as nuclear magnetic resonance structure analyses, computational structure-based design studies, and library peptides screening have recently led to the discovery and characterization of a large number of compounds belonging to different chemical families that are able to target the interaction p53-MDM2, rescuing the p53 wild-type pathway with an overall pro-apoptotic and anticancer activity. Within the preclinical assessment of these molecules, the cis-imidazoline analogue Nutlin-3 has definitely attracted great interest for its in vitro and in vivo antitumor activity in several pediatric cancer models, either as single agent on in combination with standard chemotherapy. In this light, the aim of this review is to summarize the main preclinical evidences of the potential of MDM2 inhibitors for the treatment of childhood cancers and the key suggestions coming from their assessment in the treatment of adult cancers as proof of concept for future pediatric clinical studies.
There is growing support that environmental influences and individual genetic susceptibility may increase the incidence and accelerate the onset of Alzheimer’s disease (AD). Epigenetic mechanisms ...encompass a complex regulatory network of modifications with considerable impact on health and disease risk. Abnormal epigenetic regulation is a hallmark in many pathological conditions including AD. It is well recognized that numerous bioactive dietary components mediate epigenetic modifications associated with the pathophysiology of several diseases. Although the influences of dietary factors on epigenetic regulation have been extensively investigated, only few studies have explored the effects of specific food components in regulating epigenetic patterns during neurodegeneration and AD. Epigenetic nutritional research has substantial potential for AD and may represent a window of opportunity to complement other interventions. Here, we provide a brief overview of the main mechanisms involved in AD, some of which may be epigenetically modulated by bioactive food.
The TPE-RX Neutral Beam Injector, which provides a 25
keV positive ion beam energy with a maximum current of 50
A for a pulse duration of 30
ms, will be installed on RFX-mod thanks to the agreement ...with the AIST Institute of Tsukuba (Japan). The main scientific objective is the study of the behavior of the fast ions, which in the RFP helical equilibrium have exhibited very long confinement times.
The integration of TPE-RX NBI on RFX-mod requires the development of several new components: a mechanical interface between the RFX-mod vacuum vessel and neutralizer; a Magnetic Residual Ion Dump; a new vacuum pumping system designed to maximize pumping and minimize beam stopping due to reionization.
As regards the power supplies the compliance of the Japanese equipment to the Italian safety rules has been considered and layout studies have been carried out; the integration of the NBI control system in the RFX timing sequence has been studied as well.
Interferon (IFN)- alpha affects the growth, differentiation and function of various cell types by transducing regulatory signals through the Janus tyrosine kinase/signal transducers of activation and ...transcription (Jak/STAT) pathway. The signalling pathways employing the mitogen-activated ERK-activating kinase (MEK) and the extracellular-regulated kinase (ERK) are critical in growth factors signalling. Engagement of the receptors, and subsequent stimulation of Ras and Raf, initiates a phosphorylative cascade leading to activation of several proteins among which MEK and ERK play a central role in routing signals critical in controlling cell development, activation and proliferation. We demonstrate here that 24-48 h following treatment of transformed T- and monocytoid cell lines with recombinant human IFN- alpha 2b both the phosphorylation and activity of MEK1 and its substrates ERK1/2 were reduced. In contrast, the activities of the upstream molecules Ras and Raf-1 were not affected. No effect on MEK/ERK activity was observed upon short-term exposure (1-30 min) to IFN. The anti-proliferative effect of IFN- alpha was increased by the addition in the culture medium of a specific inhibitor of MEK, namely PD98059. In conclusion, our results indicate that IFN- alpha regulates the activity of the MEK/ERK pathway and consequently modulates cellular proliferation through a Ras/Raf-independent mechanism. Targeting the MEK/ERK pathway may strengthen the IFN-mediated anti-cancer effect.
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