Boost Full Bridge Bidirectional DC/DC Converter for Supervised Aeronautical Applications

The More Electrical Aircraft concept requires electronic devices able to efficiently and safely convert electrical power between different voltage levels. The entire realization of a bidirectional DC/DC converter, from design to validation phase, is here discussed in detail. First, a boost full bridge electrical structure is selected, adopting a Parallel Input Parallel Output (PIPO) interleaving technique and an optimal turns ratio selection for the transformers in order to reduce both weight and size of the equipment. Next, modulation schemes in both step-down and step-up modes are discussed. Successively ad hoc PI regulators for both operative modes are presented. A key idea of the paper is that the converter behavior must be related not only to the control strategy but also to a global supervision logic able to safely conduct the converter operations and to react from external stimuli. Thus, a finite state machine (FSM) approach is employed. An innovative strategy called buffer mode is presented, defined as an intelligent combination of buck and boost modes. Extensive simulations and experimental results are shown, in order to confirm the effectiveness of the proposed approach

Bacterial inactivation/sterilization by argon plasma treatment on contaminated titanium implant surfaces: in vitro study

Background: Surface treatment by argon plasma is widely used as the last step of the manufacturing process of titanium implant fixtures before their sterilization by gamma rays. The possibility of using such a technology in the daily clinical practice is particularly fascinating. The aim of the present study was to assess the effects of the argon plasma treatment on different titanium implant surfaces previously exposed in vitro to bacterial contamination. Material and Methods: Sterile c.p. titanium implant discs with turned (T, Sa: 0.8μm), sandblasted/acid-etched (SAE, Sa: 1.3μm) and titanium plasma sprayed (TPS, Sa: 3.0μm) surface were used in this study. A strain of Aggregatibacter actinomycetemcomitans ATCC3718 was grown at 37°C under anaerobic conditions for 24 h and then transferred on six discs for each of the three surface types. After 24 hours, a half of the contaminated discs (control group) were directly used to evaluate the colony forming units (CFUs). The other half of the contaminated discs (test group) were treated in an argon plasma chamber for 12 minutes at room temperature prior to be analyzed for CFU counting. All assays were performed using triplicate samples of each material in 3 different experiments. Results: When the CFU counting was carried out on control discs, a total of 1.50x106±1.4x105, 1.55x106±7.07x104 and 3.15x106±2.12x105 CFU was respectively assessed for T, SAE and TPS discs, without statistically significant differences among the three surfaces. On the contrary, any trace of bacterial contamination was assessed for titanium discs treated in the argon plasma chamber prior to be analyzed, irrespectively to the implant surface tested. Conclusions: Within the limit of this study, reported data suggested that the argon plasma technology could be efficiently used to decontaminate/sterilize previously infected titanium implant surfaces

Gender-related issues in the pharmacology of new anti-obesity drugs

Four new medicines-liraglutide, lorcaserin, bupropion/naltrexone, and phentermine/topiramate-have been recently added to the pharmacological arsenal for obesity treatment and could represent important tools to manage this epidemic disease. To achieve satisfactory anti-obesity goals, the use of these new medicines should be optimized and tailored to specific patient subpopulations also by applying dose adjustments if needed. In the present review, we posit that gender could be among the factors influencing the activity of the new obesity drugs both because of pharmacokinetic and pharmacodynamic factors. Although evidence from premarketing clinical studies suggested that no dose adjustment by gender is necessary for any of these new medicines, these studies were not specifically designed to identify gender-related differences. This observation, together with the strong theoretical background supporting the hypothesis of a gender-dimorphic response, strongly call upon an urgent need of new real-life data on gender-related difference in the pharmacology of these new obesity drugs

Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death

Resveratrol (3,5,4'-trihydroxystilbene) (RSV), a polyphenol widely present in plants, exerts a neuroprotective function in several neurological conditions; it is an activator of class III histone deacetylase sirtuin1 (SIRT1), a crucial regulator in the pathophysiology of neurodegenerative diseases. By contrast, the RE1-silencing transcription factor (REST) is involved in the neurotoxic effects following exposure to polychlorinated biphenyl (PCB) mixture A1254. The present study investigated the effects of RSV-induced activation of SIRT1 on REST expression in SH-SY5Y cells. Further, we investigated the possible relationship between the non-dioxin-like (NDL) PCB-95 and REST through SIRT1 to regulate neuronal death in rat cortical neurons. Our results revealed that RSV significantly decreased REST gene and protein levels in a dose- and time-dependent manner. Interestingly, overexpression of SIRT1 reduced REST expression, whereas EX-527, an inhibitor of SIRT1, increased REST expression and blocked RSV-induced REST downregulation. These results suggest that RSV downregulates REST through SIRT1. In addition, RSV enhanced activator protein 1 (AP-1) transcription factor c-Jun expression and its binding to the REST promoter gene. Indeed, c-Jun knockdown reverted RSV-induced REST downregulation. Intriguingly, in SH-SY5Y cells and rat cortical neurons the NDL PCB-95 induced necrotic cell death in a concentration-dependent manner by increasing REST mRNA and protein expression. In addition, SIRT1 knockdown blocked RSV-induced neuroprotection in rat cortical neurons treated with PCB-95. Collectively, these results indicate that RSV via SIRT1 activates c-Jun, thereby reducing REST expression in SH-SY5Y cells under physiological conditions and blocks PCB-95-induced neuronal cell death by activating the same SIRT1/c-Jun/REST pathway

resveratrol treatment reduces the vulnerability of sh sy5y cells and cortical neurons overexpressing sod1 g93a to thimerosal toxicity through sirt1 dream pdyn pathway

Abstract In humans, mutation of glycine 93 to alanine of Cu++/Zn++ superoxide dismutase type-1 (SOD1-G93 A) has been associated to some familial cases of Amyotrophic Lateral Sclerosis (ALS). Several evidence proposed the involvement of environmental pollutants that like mercury could accelerate ALS symptoms. SH-SY5Y cells stably transfected with SOD1 and G93 A mutant of SOD1 constructs were exposed to non-toxic concentrations (0.01 μM) of ethylmercury thiosalicylate (thimerosal) for 24 h. Interestingly, we found that thimerosal, in SOD1-G93 A cells, but not in SOD1 cells, reduced cell survival. Furthermore, thimerosal-induced cell death occurred in a concentration dependent-manner and was prevented by the Sirtuin 1 (SIRT1) activator Resveratrol (RSV). Moreover, thimerosal decreased the protein expression of transcription factor Downstream Regulatory Element Antagonist Modulator (DREAM), but not DREAM gene. Interestingly, DREAM reduction was blocked by co-treatment with RSV, suggesting the participation of SIRT1 in determining this effect. Immunoprecipitation experiments in SOD1-G93 A cells exposed to thimerosal demonstrated that RSV increased DREAM deacetylation and reduced its polyubiquitination. In addition, RSV counteracted thimerosal-enhanced prodynorphin (PDYN) mRNA, a DREAM target gene. Furthermore, cortical neurons transiently transfected with SOD1-G93 A construct and exposed to thimerosal (0.5 μM/24 h) showed a reduction of DREAM and an up-regulation of the prodynorphin gene. Importantly, both the treatment with RSV or the transfection of siRNA against prodynorphin significantly reduced thimerosal-induced neurotoxicity, while DREAM knocking-down potentiated thimerosal-reduced cell survival. These results demonstrate the particular vulnerability of SOD1-G93 A neuronal cells to thimerosal and that RSV via SIRT1 counteracts the neurodetrimental effect of this toxicant by preventing DREAM reduction and prodynorphin up-regulation

TCGA Molecular Subgroups in Endometrial Undifferentiated/Dedifferentiated Carcinoma

We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer: microsatellite-instable/hypermutated (MSI), POLE-mutant/ultramutated (POLE), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-abnormal (p53abn), through a systematic review and meta-analysis. Electronic databases were searched from January 2013 to July 2019 for studies assessing the TCGA classification in endometrial UDC/DDC series. Pooled prevalence of each TCGA subgroup on the total UDC/DDCs was calculated. Three studies with 73 patients were included. Pooled prevalence of the TCGA subgroups were: 12.4% for the POLE subgroup, 44% for the MSI subgroup, 18.6% for the p53abn subgroup, 25% for the p53wt group. All TCGA groups are represented in UDC/DDC, with a predominance of the MSI group, indicating a biological heterogeneity. Hypermutated/ultramutated cancers constitute the majority of UDC/DDC, suggesting a crucial difference with other high-risk histologies of endometrial carcinoma

Mimicking the Secretory Action of a Gland by a CompositeSystem Made of a pH-Responsive Surfactant-Based Hydrogel and a DialysisMembrane

The hydrogel obtained by a zwitterionic N-oxide surfactant is proposed as the core of a pH-responsive artificial gland model. The viscosity and pH variations, induced by pulse additions of acid and base, are investigated by a pyridinium salt and alizarin red S, respectively. The artificial gland model is implemented by enclosing the gel within a dialysis membrane, and its secretory action is tested by monitoring the release of a fluorescent acridinium salt