Behaviour of structures isolated by HDNR bearings at design and service conditions

High-Damping Natural Rubber (HDNR) bearings are widely employed for seismic isolation. These bearings are characterized by a remarkable nonlinear behaviour and often by a degrading cyclic response, induced by the addition of filler to enhance its dissipation capacity. This latter phenomenon, denoted as stress-softening or Mullins effect, can significantly influence the nonlinear dynamic response of isolated structures leading to a variability of the seismic response of isolated buildings. Moreover, the behaviour of HDNR bearings may produce an amplification of response, due to higher modes contribution, which can affect the performance of non-structural components and equipment. Models providing an accurate description of the nonlinear behaviour of HDNR bearings with significant stress-softening have been proposed only recently. Thus, the studies in the literature are generally based on simplified models. In this paper, an advanced HDNR model, accounting for variation of stiffness and damping with the strain amplitude and deformation history, is used to analyse the seismic performance of isolated structures at different intensity levels. First, a parametric analysis is carried out on a two-degree of freedom system to study different configurations of practical interest. Subsequently, a multi-degree of freedom system representing a realistic building is analysed to evaluate the response at different floors and the contribution of higher modes of vibration. The influence of practical aspects, such as the superstructure damping and the friction of the sliders, is also investigated

Rapid and innovative instrumental approaches for quality and authenticity of olive oils

The quality of virgin olive oils is assessed through the determination of several analytical parameters, whose values must be within the ranges established by the different institutions involved. In addition to official methods, there is a strong need for simple, rapid, and environmentally friendly techniques for the quality control of virgin olive oils and for addressing the challenging task of determining geographical origin and detecting adulterants. Toward this purpose, some of the most interesting applications based on optical spectroscopic techniques, on the measurement of electrical characteristics and on the use of instruments equipped with electronic chemical sensors, including also other promising techniques are herein discussed. These techniques, adequately coupled with an appropriate statistical approach, appear to be promising for assessment of several quality-related parameters. The prediction of sensory attributes and of the oxidative status of virgin olive oils have also been reviewed by adopting these selected techniques, which are also considered to be potentially appropriate solutions for identification of the geographical origin of virgin olive oils and to assess their adulteration with cheaper oils. Overall, the techniques discussed are promising and cutting-edge approaches for the establishment of useful portable instruments for in situ monitoring of the quality of virgin olive oils. Practical applications: The simple, rapid, and environmentally friendly analytical approaches discussed herein represent promising analytical tools for assuring the authenticity and monitoring the quality of virgin olive oils. Such innovative techniques and tools need to be ring-tested and validated. Some innovative reviewed approaches will permit to develop useful portable instruments able to perform in situ appropriate controls also by small laboratories or olive oil mills with limited technical facilities. These equipments will be potentially usable also by trained \u201cnon-professional analytical skilled\u201d people. Some other approaches, rapid but more expensive, will be applicable mainly by quality control labs and will increase the number of samples analyzed per day, thus fostering laboratory proficiency and an effective fighting against olive oil fraud

On the importance of anandamide structural features for its interactions with DPPC bilayers: effects on PLA2 activity

The acylethanolamide anandamide (AEA) occurs in a variety of mammalian tissues and, as a result of its action on cannabinoid receptors, exhibits several cannabimimetic activities. Moreover, some of its effects are mediated through interaction with an ion channel-type vanilloid receptor. However, the chemical features of AEA suggest that some of its biological effects could be related to physical interactions with the lipidic part of the membrane. The present work studies the effect of AEA-induced structural modifications of the dipalmitoylphosphatidylcholine (DPPC) bilayer on phospholipase A2 (PLA2) activity, which is strictly dependent on lipid bilayer features. This study, performed by 2-dimethylamino-(6-lauroyl)-naphthalene fluorescence, demonstrates that the effect of AEA on PLA2 activity is concentration-dependent. In fact, at low AEA/DPPC molar ratios (from R = 0.001 to R = 0.04), there is an increase of the enzymatic activity, which is completely inhibited for R = 0.1. X-ray diffraction data indicate that the AEA affects DPPC membrane structural properties in a concentration-dependent manner. Because the biphasic effect of increasing AEA concentrations on PLA2 activity is related to the induced modifications of membrane bilayer structural properties, we suggest that AEA-phospholipid interactions may be important to produce, at least in part, some of the similarly biphasic responses of some physiological activities to increasing concentrations of AEA

A Design Method for Viscous Dampers Connecting Adjacent Structures

This paper investigates the seismic design of fluid viscous dampers connecting adjacent structural systems. A simplified dampers design strategy is proposed, which relies on a linearized reduced order model of the coupled system. A stochastic linearization technique is adopted with the aim of extending the design method to non-linear viscous dampers. The effectiveness of the design method and of the coupling strategy are assessed via numerical analysis of two adjacent buildings with shear-type behavior connected by linear or non-linear viscous dampers and subjected to Gaussian stochastic base acceleration. Different dampers locations are analyzed. The accuracy of the reduced order model is assessed, by comparing the relevant response statistics to those provided by a refined multi degree of freedoms model. Finally, a parametric study is performed to assess the effectiveness of dissipative connection for different values of seismic intensity and dampers parameters (i.e., viscous coefficients and velocity exponents)

Influence of viscous dampers ultimate capacity on the seismic reliability of building structures

Anti-seismic devices should be designed with proper safety margins against their failure, because the reliability of the structural system where they are installed is strongly influenced by their reliability. Seismic standards generally prescribe safety factors (reliability factors) amplifying the device responses at the design condition, in order to reach a target safety level. In the case of Fluid Viscous Dampers (FVDs), these factors are applied to the stroke and velocity, and their values are not homogeneous among seismic codes. This paper investigates the influence of the values of the safety factors for FVDs on the reliability of the devices and of the structural systems equipped with them. An advanced FVD model is employed to account for the impact forces arising when the dampers reach the end-stroke and the brittle failure due to the attainment of the maximum force capacity. The effect of damper failure on both the fragility and the seismic risk of the structural system is investigated by performing multiple-stripe analysis and monitoring different global and local demand parameters. In particular, a parametric study has been carried out, considering two case studies consisting of a low-rise and a medium-rise steel building, coupled with a dissipative system with linear and nonlinear properties and studying the consequences of different values of safety factors for stroke and forces. The study results give evidence to the potential brittle behaviour of the coupled system and provide information about the relationships between damper safety factors and effective structural reliability. Some preliminary suggestions are given on possible improvements of current design approaches and on the values of the reliability factors to be considered for future code revision

A Chemically Defined Medium-Based Strategy to Efficiently Generate Clinically Relevant Cord Blood Mesenchymal Stromal Colonies.

During the last decade it has been demonstrated that mesenchymal progenitors are present and can be isolated also from cord blood (CB). Recently, we managed to set up a standard protocol allowing the isolation of mesenchymal stromal cells (MSCs) with high proliferative potential and multiple differentiation capabilities, whereas the generation rate of MSC-initiating colonies could still be further improved. Herein, we strikingly succeeded in defining some simple and basic culture conditions based on the use of a chemically defined medium that increased the colony isolation efficiency up to almost 80% of processed CB units. Importantly, this result was achieved irrespective of CB unit white blood cell content and time elapsed from delivery, two limiting parameters involved with processing CB units. Thus, this high efficiency is guaranteed without strict selection of the starting material. In addition, since we are profoundly concerned about how different culture conditions can influence cell behavior, we devoted part of this study to in-depth characterization of the established CB-MSC populations to confirm their stemness features in this novel isolation and culture system. Therefore, an extended study of their immunophenotype, including classical pericytic markers, and a detailed molecular analysis addressing telomere length and also stemness-related microRNA contribution were performed. In summary, we propose a straightforward, extremely efficient, and reliable approach to isolate and expand thoroughly characterized CB-MSCs, even when poor-quality CB units are the only available source, or there is no space for an isolation to fail

Phase II Prospective Open-Label Trial of Recombinant Interleukin-11 in DDAVP-Unresponsive Von Willebrand Disease and Mild or Moderate Hemophilia A

Desmopressin (DDAVP) is the treatment of choice in those with mild von Willebrand disease (VWD), yet 20% are unresponsive to DDAVP, and among the 80% who respond, the response is transient, as endothelial stores are depleted after 3 days. We, therefore, conducted a single-center Phase II clinical trial to determine safety and biologic efficacy of recombinant interleukin-11 (rhIL-11, Neumega®) in patients with VWD unresponsive or allergic to DDAVP, or mild or moderate hemophilia A (HA). Increases in VWF:RCo were observed by 48 hours after rhIL-11, with a 1.54-fold increase by day 4, 1.30-fold in VWD and 1.73-fold in HA. Similarly, by 48 hours, increases in VIII:C were observed, with a 1.65-fold increase by day 4, 1.86-fold in VWD and 1.48-fold in HA. Platelet VWFmRNA expression by qPCR increased 0.81-fold but did not correlate with plasma VWF:Ag responses. rhIL-11 was well tolerated, with grade 1 or less fluid retention, flushing, conjunctival erythema, except for transient grade 3 hyponatremia in one subject after excess fluid intake for diabetic hyperglycemia, which resolved with fluid restriction. In summary, rhIL-11 increases VWF levels in 2 of 4 DDAVP-unresponsive or allergic VWD and F.VIII levels in 4 of 5 mild or moderate hemophilia A subjects, suggesting its potential use in treatment of these disorders

Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling

Class 2: Transcripts that are less abundant in the phr1Δ mutant than in the wild type. (XLSX 39 kb

FOXP1 circular RNA sustains mesenchymal stem cell identity via microRNA inhibition

Stem cell identity and plasticity are controlled by master regulatory genes and complex circuits also involving non-coding RNAs. Circular RNAs (circRNAs) are a class of RNAs generated from protein-coding genes by backsplicing, resulting in stable RNA structures devoid of free 5' and 3' ends. Little is known of the mechanisms of action of circRNAs, let alone in stem cell biology. In this study, for the first time, we determined that a circRNA controls mesenchymal stem cell (MSC) identity and differentiation. High-throughput MSC expression profiling from different tissues revealed a large number of expressed circRNAs. Among those, circFOXP1 was enriched in MSCs compared to differentiated mesodermal derivatives. Silencing of circFOXP1 dramatically impaired MSC differentiation in culture and in vivo. Furthermore, we demonstrated a direct interaction between circFOXP1 and miR-17-3p/miR-127-5p, which results in the modulation of non-canonical Wnt and EGFR pathways. Finally, we addressed the interplay between canonical and non-canonical Wnt pathways. Reprogramming to pluripotency of MSCs reduced circFOXP1 and non-canonical Wnt, whereas canonical Wnt was boosted. The opposing effect was observed during generation of MSCs from human pluripotent stem cells. Our results provide unprecedented evidence for a regulatory role for circFOXP1 as a gatekeeper of pivotal stem cell molecular networks

Amniotic membrane-mesenchymal stromal cells secreted factors and extracellular vesicle-miRNAs: Anti-inflammatory and regenerative features for musculoskeletal tissues

Human amniotic membrane-derived mesenchymal stromal cells (hAMSCs) are easily obtained in large quantities and free from ethical concerns. Promising therapeutic results for both hAMSCs and their secreted factors (secretome) were described by several invitro and preclinical studies, often for treatment of orthopedic disorders such as osteoarthritis (OA) and tendinopathy. For clinical translation of the hAMSC secretome as cell-free therapy, a detailed characterization of hAMSC-secreted factors is mandatory. Herein, we tested the presence of 200 secreted factors and 754 miRNAs in extracellular vesicles (EVs). Thirty-seven cytokines/chemokines were identified at varying abundance, some of which involved in both chemotaxis and homeostasis of inflammatory cells and in positive remodeling of extracellular matrix, often damaged in tendinopathy and OA. We also found 336 EV-miRNAs, 51 of which accounted for more than95% of the genetic message. A focused analysis based on miRNAs related to OA and tendinopathy showed that most abundant EV-miRNAs are teno- and chondro-protective, able to induce M2 macrophage polarization, inhibit inflammatory Tcells, and promote Treg. Functional analysis on IL-1beta treated tenocytes and chondrocytes resulted in downregulation of inflammation-associated genes. Overall, presence of key regulatory molecules and miRNAs explain the promising therapeutic results of hAMSCs and their secretome for treatment of musculoskeletal conditions and are a groundwork for similar studies in other pathologies. Furthermore, identified molecules will pave the way for future studies aimed at more sharply predicting disease-targeted clinical efficacy, as well as setting up potency and release assays to fingerprint clinical-grade batches of whole secretome or purified components