A new digital image correlation software for displacements field measurement in structural applications

Recently, there has been a growing interest in studying non-contact techniques for strain and displacement measurement. Within photogrammetry, Digital Image Correlation (DIC) has received particular attention thanks to the recent advances in the field of low-cost, high resolution digital cameras, computer power and memory storage. DIC is indeed an optical technique able to measure full field displacements and strain by comparing digital images of the surface of a material sample at different stages of deformation and thus can play a major role in structural monitoring applications. For all these reasons, a free and open source 2D DIC software, named py2DIC, was developed at the Geodesy and Geomatics Division of DICEA, University of Rome "La Sapienza". Completely written in python, the software is based on the template matching method and computes the displacement and strain fields. The potentialities of Py2DIC were evaluated by processing the images captured during a tensile test performed in the Lab of Structural Engineering, where three different Glass Fiber Reinforced Polymer samples were subjected to a controlled tension by means of a universal testing machine. The results, compared with the values independently measured by several strain gauges fixed on the samples, demonstrate the possibility to successfully characterize the deformation mechanism of the investigated material. Py2DIC is indeed able to highlight displacements at few microns level, in reasonable agreement with the reference, both in terms of displacements (again, at few microns in the average) and Poisson's module

d aspartate exerts an opposing role upon age dependent nmdar related synaptic plasticity and memory decay

In the present study, we demonstrated that D-aspartate acts as an _in vitro_ and _in vivo_ neuromodulatory molecule upon hippocampal NMDAR transmission. Accordingly, we showed that this D-amino acid, widely expressed during embryonic phase, was able to strongly influence hippocampus-related functions at adulthood. Thus, while up-regulated levels of D-aspartate increased LTP and spatial memory in four-month old adult mice, the prolonged deregulation of this molecule in thirteen-month old animals induced a substantial acceleration of age-dependent decay of synaptic plasticity and cognitive functions. Moreover, we highlighted a role for D-aspartate in enhancing NMDAR-dependent synaptic plasticity through an inducible "turn-on/turn-off-like mechanism". Strikingly, we also showed that D-aspartate, when administered to aged mice, strongly rescued their physiological synaptic decay and attenuated their cognitive deterioration. In conclusion, our data suggest a tantalizing hypothesis for which this in-embryo-occurring D-amino acid, might disclose plasticity windows in the aging brain

Physical Exercise and Alzheimer's Disease: Effects on Pathophysiological Molecular Pathways of the Disease

Alzheimer's disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD

Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release

Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a critical step for neuronal death occurring in several neurological conditions. JNKs can be activated via receptor tyrosine kinases, cytokine receptors, G-protein coupled receptors and ligand-gated ion channels, including the NMDA glutamate receptors. While JNK has been generally associated with postsynaptic NMDA receptors, its presynaptic role remains largely unexplored. Here, by means of biochemical, morphological and functional approaches, we demonstrate that JNK and its scaffold protein JIP1 are also expressed at the presynaptic level and that the NMDA-evoked glutamate release is controlled by presynaptic JNK-JIP1 interaction. Moreover, using knockout mice for single JNK isoforms, we proved that JNK2 is the essential isoform in mediating this presynaptic event. Overall the present findings unveil a novel JNK2 localization and function, which is likely to play a role in different physiological and pathological conditions

hMENA isoforms regulate cancer intrinsic type I IFN signaling and extrinsic mechanisms of resistance to immune checkpoint blockade in NSCLC

BACKGROUND: Understanding how cancer signaling pathways promote an immunosuppressive program which sustains acquired or primary resistance to immune checkpoint blockade (ICB) is a crucial step in improving immunotherapy efficacy. Among the pathways that can affect ICB response is the interferon (IFN) pathway that may be both detrimental and beneficial. The immune sensor retinoic acid-inducible gene I (RIG-I) induces IFN activation and secretion and is activated by actin cytoskeleton disturbance. The actin cytoskeleton regulatory protein hMENA, along with its isoforms, is a key signaling hub in different solid tumors, and recently its role as a regulator of transcription of genes encoding immunomodulatory secretory proteins has been proposed. When hMENA is expressed in tumor cells with low levels of the epithelial specific hMENA11a isoform, identifies non-small cell lung cancer (NSCLC) patients with poor prognosis. Aim was to identify cancer intrinsic and extrinsic pathways regulated by hMENA11a downregulation as determinants of ICB response in NSCLC. Here, we present a potential novel mechanism of ICB resistance driven by hMENA11a downregulation. METHODS: Effects of hMENA11a downregulation were tested by RNA-Seq, ATAC-Seq, flow cytometry and biochemical assays. ICB-treated patient tumor tissues were profiled by Nanostring IO 360 Panel enriched with hMENA custom probes. OAK and POPLAR datasets were used to validate our discovery cohort. RESULTS: Transcriptomic and biochemical analyses demonstrated that the depletion of hMENA11a induces IFN pathway activation, the production of different inflammatory mediators including IFNβ via RIG-I, sustains the increase of tumor PD-L1 levels and activates a paracrine loop between tumor cells and a unique macrophage subset favoring an epithelial-mesenchymal transition (EMT). Notably, when we translated our results in a clinical setting of NSCLC ICB-treated patients, transcriptomic analysis revealed that low expression of hMENA11a, high expression of IFN target genes and high macrophage score identify patients resistant to ICB therapy. CONCLUSIONS: Collectively, these data establish a new function for the actin cytoskeleton regulator hMENA11a in modulating cancer cell intrinsic type I IFN signaling and extrinsic mechanisms that promote protumoral macrophages and favor EMT. These data highlight the role of actin cytoskeleton disturbance in activating immune suppressive pathways that may be involved in resistance to ICB in NSCLC

R.C. square sections confined by FRP: A numerical procedure for predicting stress–strain relationships

The effects of confinement on concrete elements subjected to axial load are well known: the resulting axial stress–strain relationship shows higher strength and ultimate strain with respect to the unconfined one. Several studies have been devoted to the understanding of the behavior of circular concrete sections while comparatively fewer studies have dealt with square and rectangular ones. Regarding square and rectangular sections, the so called “arching effect” is usually considered in order to define an equivalent reduced area, which is supposed as efficient as a circular section. Inside the equivalent area the stress induced by the confinement is considered uniformly distributed, even if it is not so, as already discussed in [17] where further on a strength criterion has been proposed for predicting the material strength increase, based on a revision of the classical strength criterion reported in [18]. That strength criterion, along with the methodology here proposed, are the basis of a procedure meant to develop a mechanics-based stress–strain relationship for FRP-confined concrete which stems from a step-by-step analysis of the behavior of FRP-confined square concrete sections

Square and rectangular concrete columns confined by CFRP: Experimental and numerical investigation

The results of an experimental and theoretical investigation into the deformation behavior of CFRP-confined square and rectangular concrete columns under axial loads are presented. Three types of columns are considered: unwrapped; fully wrapped; and fully wrapped, with L-slaped steel angles placed at the corners. A mechanical deformation model for them is proposed, which is based on a nonuniform distribution of the stresses caused by the confining device. The results given by the model are in a good agreement with the experimental results obtained

A split-wedge anchorage for CFRP cables: numerical model vs. experimental results

Fiber-reinforced polymers (FRPs) are widely used within civil structural applications either for structural retrofitting or new constructions. This is due to their appreciable mechanical properties such as high stiffness and strength, resistance to environmental effects, as well low density. Through the years, such peculiarities have encouraged researchers to apply FRP cables within the design of prestressing systems, where steel cables are systematically adopted. However, the brittleness intrinsic to FRP materials necessitates additional efforts to design the anchorage devices. In fact, tendons are here subjected to stress peaks, which need to be controlled in order to prevent the premature failure of the cable. Following this goal, authors recently studied an optimized split-wedge anchorage, for 12 mm-diameter pultruded-carbon-fiber-reinforced polymer (PCFRP) tendons, adopting double-angle (DA) wedges, and compared its performance with a single-angle (SA) wedge configuration. Tensile tests were performed on 3 SA and 2 DA prototypes, respectively, through a universal testing machine: the DA configuration exploited the average cable capacity (257 kN) once, denoting a maximum efficiency. The obtained experimental results are utilized, in the framework of the present work, to calibrate contact parameters of nonlinear finite element models. The presented numerical results helped to assess benefits of the proposed configurations and the behavior of the anchorage components: the DA configuration turned out to satisfactorily avoid stress peak superpositions on the cable, with a reduction in pressure in the loading end of the cable with respect to the SA model

Square concrete section confined by FRP: ultimate strength prediction

During the last ten years, several studies have been devoted to understanding the behaviour of circular concrete sections confined by FRP. Less studies have dealt with square and rectangular sections, even if the problem is equally important, given the large amount of buildings with such sections that need to be retrofitted due to poor performance under vertical and horizontal actions. A numerical model was already proposed for the prediction of the stress-strain relationship. In order to implement such model in a design code framework, a mechanics-based equation has been developed and preliminary results are presented for the prediction of the ultimate strength of square sections confined by FRP. Since the model consider the corner radius influence, circular sections are automatically included as a particular case. The simplified model has been tested against a set of experimental values available in the literature: the comparison was satisfactory and its accuracy is discussed

Analytical modeling of square and rectangular concrete columns confined by FRP: ultimate strength prediction

An analytical model tailored for the ultimate stress prediction of the FRP confined concrete section is presented. The model has been conceived to be implemented in a design code and a simple yet robust mechanics-based equation has been developed and tested against a set of experimental literature data. The model is thought for square/rectangular sections and considers the corner radius influence, so that circular sections are automatically included as a particular case