Seismic reliability analysis of isolated deck bridges using friction pendulum devices

In this study, the seismic reliability of multi-span continuous deck bridges equipped with isolation friction pendulum (FP) devices is investigated. The relevant aleatory uncertainties associated to the sliding friction coefficient of the FP isolators and to the seismic inputs are considered. A six-degree-of-freedom model is established to reproduce the elastic behavior of the reinforced concrete (RC) pier, the stiff response of the deck supported by the isolation devices and the non-linear response of the FPS bearings which depends on the sliding velocity. Moreover, the RC abutment is assumed as infinitely rigid. For what concerns the seismic inputs, a group of natural seismic records having various characteristics is adopted and properly scaled to increasing levels of intensity. The random variability of the friction coefficient is modelled by suitable probabilistic distribution. Then, considering several bridges and isolator configurations, the fragility curves of the RC pier and of the isolator devices (FP) are determined. Finally, in agreement with the hazard curve of the specific site, the convolution integral is adopted to determine the seismic reliability curves in the performance domain

Targeting RyR Activity Boosts Antisense Exon 44 and 45 Skipping in Human DMD Skeletal or Cardiac Muscle Culture Models.

Systemic delivery of antisense oligonucleotides (AO) for DMD exon skipping has proven effective for reframing DMD mRNA, rescuing dystrophin expression, and slowing disease progression in animal models. In humans with Duchenne muscular dystrophy treated with AOs, low levels of dystrophin have been induced, and modest slowing of disease progression has been observed, highlighting the need for improved efficiency of human skipping drugs. Here, we demonstrate that dantrolene and Rycals S107 and ARM210 potentiate AO-mediated exon skipping of exon 44 or exon 45 in patient-derived myotube cultures with appropriate mutations. Further, dantrolene is shown to boost AO-mediated exon skipping in patient-derived, induced cardiomyocyte cultures. Our findings further validate the ryanodine receptors (RyR) as the likely target responsible for exon skip boosting and demonstrate potential applicability beyond exon 51 skipping. These data provide preclinical support of dantrolene trial as an adjuvant to AO-mediated exon-skipping therapy in humans and identify a novel Rycal, ARM210, for development as a potential exon-skipping booster. Further, they highlight the value of mutation-specific DMD culture models for basic discovery, preclinical drug screening and translation of personalized genetic medicines

Main Fuel Cells mathematical models: Comparison and analysis in terms of free parameters

This paper resumes the main mathematical models of Fuel Cells (PEM models). In particular, a comparison study of the various models introduced in the technical literature is presented and the dependency of the various model parameters is analyzed in different operating conditions. As the manifold of the model parameter is very wide and their determination is difficult, it is mandatory to introduce approximations and simplifications on which each model is based. The novelty of this work is the organization of the existing models in three categories with regard to the number of free parameters and to the dependency of such parameters on the different running conditions and the usage of a reference model in order to compare the difference between the latter once both in terms of fast execution of the simulation and care of the simulation results

First Measurements with NeXtRAD, a Polarimetric X/L Band Radar Network

NeXtRAD is a fully polarimetric, X/L Band radar network. It is a development of the older NetRAD system and builds on the experience gained with extensive deployments of NetRAD for sea clutter and target measurements. In this paper we will report on the first measurements with NeXtRAD, looking primarily at sea clutter and some targets, as well as early attempts at calibration using corner reflectors, and an assessment of the polarimetric response of the system. We also highlight innovations allowing for efficient data manipulation post measurement campaigns, as well as the plans for the coming years with this system

Hypergrowth mTORC1 signals translationally activate the ARF tumor suppressor checkpoint

The ARF tumor suppressor is a potent sensor of hyperproliferative cues emanating from oncogenic signaling. ARF responds to these cues by eliciting a cell cycle arrest, effectively abating the tumorigenic potential of these stimuli. Prior reports have demonstrated that oncogenic Ras(V12) signaling induces ARF through a mechanism mediated by the Dmp1 transcription factor. However, we now show that ARF protein is still induced in response to Ras(V12) in the absence of Dmp1 through the enhanced translation of existing Arf mRNAs. Here, we report that the progrowth Ras/tuberous sclerosis complex (TSC)/mTORC1 signaling pathway regulates ARF protein expression and triggers ARF-mediated tumor suppression through a novel translational mechanism. Hyperactivation of mTORC1 through Tsc1 loss resulted in a significant increase in ARF expression, activation of the p53 pathway, and a dramatic cell cycle arrest, which were completely reversed upon Arf deletion. ARF protein induced from Ras(V12) in the absence of Dmp1 repressed anchorage-independent colony formation in soft agar and tumor burden in an allograft model. Taken together, our data demonstrate the ability of the ARF tumor suppressor to respond to hypergrowth stimuli to prevent unwarranted tumor formation

New insights about the putative role of myokines in the context of cardiac rehabilitation and secondary cardiovascular prevention.

Exercise training prevents the onset and the development of many chronic diseases, acting as an effective tool both for primary and for secondary prevention. Various mechanisms that may be the effectors of these beneficial effects have been proposed during the past decades: some of these are well recognized, others less. Muscular myokines, released during and after muscular contraction, have been proposed as key mediators of the systemic effects of the exercise. Nevertheless the availability of an impressive amount of evidence regarding the systemic effects of muscle-derived factors, few studies have examined key issues: (I) if skeletal muscle cells themselves are the main source of cytokine during exercise; (II) if the release of myokines into the systemic circulation reach an adequate concentration to provide significant effects in tissues far from skeletal muscle; (III) what may be the role carried out by muscular cytokine regarding the well-known benefits induced by regular exercise, first of all the anti-inflammatory effect of exercise. Furthermore, a greater part of our knowledge regarding myokines derives from the muscle of healthy subjects. This knowledge may not necessarily be transferred per se to subjects with chronic diseases implicating a direct or indirect muscular dysfunction and/or a chronic state of inflammation with persistent immune-inflammatory activation (and therefore increased circulating levels of some cytokines): cachexia, sarcopenia due to multiple factors, disability caused by neurological damage, chronic congestive heart failure (CHF) or coronary artery disease (CAD). A key point of future studies is to ascertain how is modified the muscular release of myokines in different categories of unhealthy subjects, both at baseline and after rehabilitation. The purpose of this review is to discuss the main findings on the role of myokines as putative mediators of the therapeutic benefits obtained through regular exercise in the context of secondary cardiovascular prevention

Occult renal dysfunction:a mortality and morbidity risk factor in coronary artery bypass grafting surgery

ObjectiveElevated preoperative serum creatinine is considered an independent risk factor for postoperative mortality and morbidity in patients undergoing coronary artery bypass grafting. However, the impact of occult renal dysfunction, defined as an impairment of glomerular filtration rate with normal serum creatinine, is still unknown. The aim of this study was to analyze the effects of occult renal dysfunction on early outcomes after coronary artery bypass grafting.MethodsThis was a retrospective, observational, cohort study of prospectively collected data on 9159 consecutive patients with normal serum creatinine levels undergoing coronary artery bypass grafting between April 1996 and February 2009. Patients were divided into two groups based on preoperative creatinine clearance estimated with the Cockcroft-Gault equation: 5484 patients with a creatinine clearance ≥ 60 mL/min and 3675 patients with a creatinine clearance < 60 mL/min (occult renal dysfunction group).ResultsOverall in-hospital mortality was 1%. Occult renal dysfunction was associated with a doubling in the risk of operative mortality (1.4% vs 0.7%; P = .001), postoperative renal dysfunction (5.1% vs 2.5%; P < .0001), and need for dialysis (0.8% vs 0.4%; P = .014). Moreover, occult renal dysfunction increased the risk of stroke (1% vs 0.3%; P < .0001), arrhythmia (28.5% vs 21.2%; P < .0001), and hospital stay > 7 days (36.45 vs 24.5%; P < .0001). In a multivariable analysis adjusting for preoperative risk factors, occult renal dysfunction was confirmed to be an independent predictor of mortality (odds ratio, 1.72), postoperative renal dysfunction (odds ratio, 1.9), dialysis (odds ratio, 1.82), stroke (odds ratio, 2.6) arrhythmia (odds ratio, 1.42), and hospital stay > 7 days (odds ratio, 1.65).ConclusionsOccult renal dysfunction is an independent risk factor for early mortality and morbidity in patients undergoing coronary artery bypass grafting