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The existing Reinforced Concrete (RC) buildings stock is often characterized by a significant seismic vulnerability, due to the absence of capacity design principles, even in regions with high seismic hazard, such as Italy. Approximately 67% of existing RC buildings in Italy have been designed without considering seismic actions (GLD), resulting in very low transverse reinforcement amount in beams and, particularly, in columns. Additionally, beam-column joints typically totally lack stirrups. Consequently, shear failures under seismic actions are very likely for this pre-code building typology, often limiting their seismic capacity. However, the assessment of shear failures in beams/columns or joints varies significantly from code to code worldwide. The main goal of this work is to quantify the impact of different code-based brittle capacity models on the seismic capacity assessment and retrofit, focusing on GLD Italian pre-1970 RC buildings. This comparative analysis is carried out by first considering three current codes, emphasizing their, even significant, differences: European (EN 1998-3-1. 2005), Italian (D.M. 2018), and American (ASCE SEI/41 2017) standards. Then, shear capacity models prescribed by the current drafts of the next generation of Eurocodes are implemented and compared to the current models. The assessment includes: (i) a parametric comparison among models; (ii) the evaluation of case-study buildings capacity in their as-built condition and after shear strengthening interventions. The latter is performed on 3D "bare" models, due to the lack of practical guidance in most codes on modelling masonry infills. [ABSTRACT FROM AUTHOR]

This study investigates the seismic response of archetype infilled reinforced concrete buildings representative of the existing Italian residential building stock by focusing on the modelling aspects of the existing infills, including their failure modes and interaction with the frame. The study compares the seismic response of the considered buildings, investigated through nonlinear static and dynamic analysis, with reference to two Performance Levels. The main variables considered are the construction period, the site hazard, the number of stories and the infill configuration. The observed return period capacity of the buildings mainly depends on the site hazard and on the construction period. [ABSTRACT FROM AUTHOR]

This study investigates the seismic response of reinforced concrete buildings designed according to Italian regulations and construction practices for three different post-WWII periods, up to the 1990s. Additional key investigated parameters are the number of stories and the site hazard. The main issues related to non-seismic and early seismic design practices are discussed. The study compares the seismic response of the buildings, investigated through nonlinear static and dynamic analyses, with reference to two performance levels, confirming and quantifying the increase in performance with the design codes evolution. The seismic behavior of infilled frames is investigated in the companion paper. [ABSTRACT FROM AUTHOR]

A large part of the existing building stock was not designed according to the current codes in seismic prone regions. The poor performance of some reinforced concrete structures was related to the presence of the masonry infill walls. Although the infill walls can increase the lateral resistance of frames in many cases, it is widely recognized that there is a high vulnerability of the masonry infill walls subjected to loadings along and perpendicular to their plane. Several collapses were observed after past earthquakes in infilled frame buildings. For this reason, different retrofitting design approaches have been proposed and used during the last years; however, many of them do not fit with the building's owners' economic demands or technical knowledge of the workmanship. Over the years, significant research has been conducted for masonry wall elements retrofitted with textile-reinforced mortar (TRM). However, much less has been carried for masonry-infilled frame RC frames. Thus, this manuscript aims to provide a literature review about research on assessing the effectiveness of using TRM technique to reduce masonry-infilled RC frames' seismic vulnerability. Experimental findings will be deeply analysed to provide full insight concerning the TRM's efficiency under in-plane and/or out-of-plane demands of infilled frames and some variables such as anchorage of the TRM to the structure. Numerical modelling approaches to simulate the complex behaviour of infilled frames with TRM are also presented to stress their benefits or limits. Covering completely all aspects of this manuscript is essential to briefly describe the studies conducted so far to examine either numerically or experimentally the effectiveness of using TRM for retrofitting masonry wall elements. [ABSTRACT FROM AUTHOR]

This work aims estimating seismic losses in residential-reinforced concrete buildings, highlighting the influence of infills and services. First, the mechanical-based "POST"-method is used to perform simplified (nonlinear static) structural analyses, in the "shear-type" building hypothesis. Then, drift-based fragility curves and repair cost analysis, specific for infills and services, are used to obtain expected damage and losses. Lastly, the whole proposed loss assessment methodology is applied to a wide building stock struck by L'Aquila (Italy) 2009-earthquake and damaged to infills. The numerical-versus-observed comparison of damage scenario and seismic losses allows a promising validation of the procedure. [ABSTRACT FROM AUTHOR]

Research efforts are still required for modelling the seismic behaviour of infilled frames, especially for existing buildings, generally characterised by shear failures. This work discusses the experimental seismic behaviour and the related modelling of four conforming (compliant with modern seismic codes) and non-conforming (gravity-loads-designed) Reinforced Concrete (RC) frames with and without infills (with hollow-clay bricks). The experimental results are analysed, showing that non-conforming frames exhibited shear failures involving the infill panel and the RC columns/joints. A proposed modelling approach able to reproduce these shear failures is carried out, providing support towards more reliable numerical simulations of RC buildings. [ABSTRACT FROM AUTHOR]

The mammalian brain stores and distinguishes among episodic memories, i.e. memories formed during the personal experience, through a mechanism of pattern separation computed in the hippocampal dentate gyrus. Decision-making for food-related behaviors, such as the choice and intake of food, might be affected in obese subjects by alterations in the retrieval of episodic memories. Adult neurogenesis in the dentate gyrus regulates the pattern separation. Several molecular factors affect adult neurogenesis and exert a critical role in the development and plasticity of newborn neurons. Orexin-A/hypocretin-1 and downstream endocannabinoid 2-arachidonoylglycerol signaling are altered in obese mice. Here, we show that excessive orexin-A/2-arachidonoylglycerol/cannabinoid receptor type-1 signaling leads to the dysfunction of adult hippocampal neurogenesis and the subsequent inhibition of plasticity and impairment of pattern separation. By inhibiting orexin-A action at orexin-1 receptors we rescued both plasticity and pattern separation impairment in obese mice, thus providing a molecular and functional mechanism to explain alterations in episodic memory in obesity. The authors show that adult hippocampal neurogenesis is altered in the dentate gyrus of obese mice with subsequent inhibition of long-term potentiation and impairment of pattern separation. Inhibition of orexin-A action at orexin-1 receptors rescued both impairments in obese mice. [ABSTRACT FROM AUTHOR]

Lysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism. Lysosomal storage disorders, characterized by altered metabolism of heparan sulfate, cause autistic symptoms followed by dementia in children. Here, the authors show that embryonic dopaminergic neurodevelopmental defects due to altered function of heparan sulfate cause autistic behaviours in mice. [ABSTRACT FROM AUTHOR]

The reliable estimation of seismic losses due to damage to buildings is paramount for the post-emergency management and the planning of recovery activities. For residential reinforced concrete (RC) infilled buildings, a significant role in the computation of seismic loss is played by non-structural components, above all infills, partitions and services, as shown in past earthquakes. In this work, a component-based methodology is proposed to assess seismic losses for residential RC buildings in Mediterranean region. The attention is focused on the repairing activities for masonry infills (typical enclosure or partitions elements in Italian and Mediterranean RC buildings), and for services (plumbing systems, electric equipment, floor/wall tiles...), commonly enclosed within the infill panels for the considered building typology. The described methodology can be used starting from the expected damage level to infills and partitions. It adopts given repair unit costs at different damage states of infills. The loss estimation methodology has been, first, validated by comparing predicted and actual repair costs for specific case-study buildings damaged by L'Aquila (Italy) 2009 earthquake. Then, the methodology has been applied to a wide dataset of RC buildings (about 2500 residential buildings) damaged by L'Aquila earthquake available from the literature, to show its possible application at a large-scale level. A good agreement between observed and predicted costs is obtained both for specific case-study buildings and for the wider building stock, especially when damage to structural components is very limited. [ABSTRACT FROM AUTHOR]

Experimental works in literature have paid proper attention to the seismic response of hollow circular piers only quite recently, despite their widespread use in existing bridges. Herein, experimental cyclic tests on two scaled reinforced concrete piers with hollow circular cross-section, representative of typical existing Italian bridges, are carried out. Design criteria, adopted setup, experimental response, and damage evolution are discussed. A focus on shear–critical piers is performed, collecting an experimental database of tests from literature. The more specific existing shear strength models are compared with the collected data. Model by Ranzo and Priestley [2001] has finally shown promising results. [ABSTRACT FROM AUTHOR]

Autophagy agonists have been proposed to slow down neurodegeneration. Spermidine, a polyamine that acts as an autophagy agonist, is currently under clinical trial for the treatment of age‐related memory decline. How Spermidine and other autophagy agonists regulate memory and synaptic plasticity is under investigation. We set up a novel mouse model of mild cognitive impairment (MCI), in which middle‐aged (12‐month‐old) mice exhibit impaired memory capacity, lysosomes engulfed with amyloid fibrils (β‐amyloid and α‐synuclein) and impaired task‐induced GluA1 hippocampal post‐translation modifications. Subchronic treatment with Spermidine as well as the autophagy agonist TAT‐Beclin 1 rescued memory capacity and GluA1 post‐translational modifications by favouring the autophagy/lysosomal‐mediated degradation of amyloid fibrils. These findings provide new mechanistic evidence on the therapeutic relevance of autophagy enhancers which, by improving the degradation of misfolded proteins, slow down age‐related memory decline. [ABSTRACT FROM AUTHOR]

The presence of α-synuclein aggregates in the retina of Parkinson's disease patients has been associated with vision impairment. In this study we sought to determine the effects of α-synuclein overexpression on the survival and function of dopaminergic amacrine cells (DACs) in the retina. Adult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type α-synuclein in the inner retina. Before and after systemic injections of levodopa (L-DOPA), retinal responses and visual acuity-driven behavior were measured by electroretinography (ERG) and a water maze task, respectively. Amacrine cells and ganglion cells were counted at different time points after the injection. α-synuclein overexpression led to an early loss of DACs associated with a decrease of light-adapted ERG responses and visual acuity that could be rescued by systemic injections of L-DOPA. The data show that α-synuclein overexpression affects dopamine neurons in the retina. The approach provides a novel accessible method to model the underlying mechanisms implicated in the pathogenesis of synucleinopathies and for testing novel treatments. [ABSTRACT FROM AUTHOR]

This study aims contributing to the investigation about the shear strength of reinforced concrete members with hollow circular cross-section and ordinary concrete strength. First, a proper experimental database of tests carried out in the literature on hollow circular members is collected and analysed. Then, the few existing shear strength models from the literature or seismic codes considered suitable for hollow circular sections are discussed and compared with the experimental results. Starting from the lonely specific degrading model existing in the literature, new equations are proposed on mechanical bases for concrete, transverse reinforcement and axial load contributions to the shear strength and for the shear strength degradation due to increasing ductility demand. The new proposed model is finally validated by means of the collected experimental data. Numericalversus-experimental comparisons show very good results in terms of predicting capacity of both maximum (not-degraded) and degraded shear strength. The relative percentage prediction error always results lower than 4% with a very limited dispersion. The proposed equations can be thus considered as a reliable improvement of existing shear strength models for the investigated structural typology. [ABSTRACT FROM AUTHOR]

Earthquakes that have occurred in the last twenty years in the Mediterranean area have had significant economic and social impacts. Most of the economic losses of reinforced concrete (RC) frames was due to nonstructural component damage, particularly masonry infills and partitions. Therefore, the seismic behaviour of masonry infills should be reliably characterized. The main goals of this study for a more reliable loss estimation for infilled RC frames are: (i) the analysis of the inter-story drift ratio (IDR) capacity at given damage states (DSs) with the aim to define drift-based fragility functions and (ii) analyse direct losses due to infill damage following seismic events. First, a database of experimental tests performed on 1-bay, 1-story scaled RC frames infilled with clay bricks or concrete blocks is collected. Drift-based fragility curves are obtained, which depend on the infill brick materials and properties. Then, the drift capacity threshold at each DS is correlated to the in-plane response of the infill panel to directly quantify the relationship that exists among them. The influence of openings on drift capacities is also evaluated. Then, seismic losses related to infills are computed, providing expected monetary losses depending on the infill typology. The required reparation activities and their costs are also listed. The bearing of each activity and cost at each DS is explicitly evaluated. Additionally, loss functions that directly depend on IDR demand are provided, thus fusing together the damage analysis and loss analysis. Finally, a simplified formulation for loss functions is proposed for a simple, practice-oriented loss calculation. [ABSTRACT FROM AUTHOR]

Most of the existing Reinforced Concrete (RC) bridges were designed before the recent advancements in earthquake engineering and seismic codes. The performance assessment of these bridges is, therefore, a crucial issue for seismic safety of bridge infrastructures and estimation of losses due to seismic events. Despite the seismic assessment of columns with solid cross-section in ordinary buildings may be considered as quite comprehensive, a similar conclusion cannot be drawn for shear-critical hollow core piers, widespread in existing bridge structures. The present work aims at contributing to the investigation about the response of RC piers with hollow rectangular cross-section under cyclic loading. The main goal of the study is the definition of a comprehensive and practice-oriented modelling approach for the assessment of seismic response of RC hollow rectangular piers, able to account for all the deformability contributions, and, particularly, able to reliably predict drift-capacity at shear failure and subsequent degrading stiffness. A three-component model, accounting for flexural flexibility, shear flexibility and slippage of rebars is adopted. The shear capacity assessment is dealt with more in details. A proper experimental database is collected, made up of cyclic tests on hollow rectangular piers failing in shear, with or without yielding of longitudinal reinforcing bars. A new empirical formulation for the assessment of the displacement capacity at shear failure, specifically for the investigated structural elements, is calibrated. The degrading stiffness also is empirically calibrated to completely define the degrading shear response. Finally, the proposed numerical model is validated through the comparison with the experimental results carried out by the Authors (also in terms of local deformability contributions) and with test results collected from literature, proving that it can be a simple and reliable tool for the seismic assessment of existing shear-critical bridge piers. [ABSTRACT FROM AUTHOR]

Experimental tests on four full-scale exterior unreinforced reinforced concrete (RC) beam-column joints, representative of the existing non-conforming RC frame buildings, are carried out. The specimens have different longitudinal reinforcements (plain or deformed) and they are designed in order to be representative of two typical design practices (for gravity loads only or according to an obsolete seismic code). Different failure modes are observed, namely joint failure with or without beam yielding. The local response of the joint panel is analyzed. The different joint deformation mechanisms and their contribution to the deformability and to the energy dissipation capacity of the sub-assemblages are evaluated. [ABSTRACT FROM AUTHOR]

Nigro-striatal dopamine transmission is central to a wide range of neuronal functions, including skill learning, which is disrupted in several pathologies such as Parkinson's disease. The synaptic plasticity mechanisms, by which initial motor learning is stored for long time periods in striatal neurons, to then be gradually optimized upon subsequent training, remain unexplored. Addressing this issue is crucial to identify the synaptic and molecular mechanisms involved in striatal-dependent learning impairment in Parkinson's disease. In this study, we took advantage of interindividual differences between outbred rodents in reaching plateau performance in the rotarod incremental motor learning protocol, to study striatal synaptic plasticity ex vivo. We then assessed how this process is modulated by dopamine receptors and the dopamine active transporter, and whether it is impaired by overexpression of human α-synuclein in the mesencephalon; the latter is a progressive animal model of Parkinson's disease. We found that the initial acquisition of motor learning induced a dopamine active transporter and D1 receptors mediated long-term potentiation, under a protocol of long-term depression in striatal medium spiny neurons. This effect disappeared in animals reaching performance plateau. Overexpression of human α-synuclein reduced striatal dopamine active transporter levels, impaired motor learning, and prevented the learning-induced long-term potentiation, before the appearance of dopamine neuronal loss. Our findings provide evidence of a reorganization of cellular plasticity within the dorsolateral striatum that is mediated by dopamine receptors and dopamine active transporter during the acquisition of a skill. This newly identified mechanism of cellular memory is a form of metaplasticity that is disrupted in the early stage of synucleinopathies, such as Parkinson's disease, and that might be relevant for other striatal pathologies, such as drug abuse. [ABSTRACT FROM AUTHOR]

This study investigates the seismic response of reinforced concrete buildings designed according to the current Italian building code. Number of stories, site hazard, presence and distribution of masonry infill panels, and type of lateral resisting system are the key investigated parameters. The main issues related to design and modeling are discussed. Two Limit States are considered, namely Global Collapse and Usability-Preventing Damage. The main aim of the study is a comparison between the seismic response of the buildings, investigated through nonlinear static and dynamic analyses. Irregularity in the distribution of infill panels and site hazard emerge as the most influential parameters. [ABSTRACT FROM AUTHOR]

The seismic response of non-ductile reinforced concrete (RC) buildings can be affected by the behaviour of beam-column joints involved in the failure mechanism, especially in typical existing buildings. Conventional modelling approaches consider only beam and column flexibility, although joints can provide a significant contribution also to the overall frame deformability. In this study, the attention is focused on exterior joints without transverse reinforcement, and a possible approach to their modelling in nonlinear seismic analysis of RC frames is proposed. First, experimental tests performed by the authors are briefly presented, and their results are discussed. Second, these tests, together with other tests with similar features from literature, are employed to calibrate the joint panel deformability contribution in order to reproduce numerically the experimental joint shear stress-strain behaviour under cyclic loading. After a validation phase of this proposal, a numerical investigation of the influence of joints on the seismic behaviour of a case study RC frame - designed for gravity loads only - is performed. The preliminary failure mode classification of the joints within the analysed frame is carried out. Structural models that (i) explicitly include nonlinear behaviour of beam-column joints exhibiting shear or anchorage failure or (ii) model joints as elements with infinite strength and stiffness are built and their seismic performance are assessed and compared. A probabilistic assessment based on nonlinear dynamic simulations is performed by means of a scaling approach to evaluate the seismic response at different damage states accounting for uncertainties in ground-motion records. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Lysosomal storage disorders ( LSDs) are inherited diseases characterized by lysosomal dysfunction and often showing a neurodegenerative course. There is no cure to treat the central nervous system in LSDs. Moreover, the mechanisms driving neuronal degeneration in these pathological conditions remain largely unknown. By studying mouse models of LSDs, we found that neurodegeneration develops progressively with profound alterations in presynaptic structure and function. In these models, impaired lysosomal activity causes massive perikaryal accumulation of insoluble α-synuclein and increased proteasomal degradation of cysteine string protein α ( CSPα). As a result, the availability of both α-synuclein and CSPα at nerve terminals strongly decreases, thus inhibiting soluble NSF attachment receptor ( SNARE) complex assembly and synaptic vesicle recycling. Aberrant presynaptic SNARE phenotype is recapitulated in mice with genetic ablation of one allele of both CSPα and α-synuclein. The overexpression of CSPα in the brain of a mouse model of mucopolysaccharidosis type IIIA, a severe form of LSD, efficiently re-established SNARE complex assembly, thereby ameliorating presynaptic function, attenuating neurodegenerative signs, and prolonging survival. Our data show that neurodegenerative processes associated with lysosomal dysfunction may be presynaptically initiated by a concomitant reduction in α-synuclein and CSPα levels at nerve terminals. They also demonstrate that neurodegeneration in LSDs can be slowed down by re-establishing presynaptic functions, thus identifying synapse maintenance as a novel potentially druggable target for brain treatment in LSDs. [ABSTRACT FROM AUTHOR]

Recent earthquakes have confirmed the role played by infills in the seismic response of reinforced concrete buildings. The control and limitation of damage to such nonstructural elements is a key issue in performance-based earthquake engineering. The present work is focused on modeling and analysis of damage to infill panels, and, in particular, it is aimed towards linear analysis procedures for assessing the damage limitation limit state of infilled reinforced concrete frames. First, code provisions on infill modeling and acceptance criteria at the damage limitation limit state are reviewed. Literature contributions on damage to unreinforced masonry infill panels and corresponding displacement capacity are reported and discussed. Two procedures are then proposed aiming at a twofold goal: (i) the determination of 'equivalent' interstory drift ratio limits for a bare frame model and (ii) the estimation of the stiffness of equivalent struts representing infill walls in a linear model. These two quantities are determined such that a linear model ensures a reliable estimation of seismic capacity at the damage limitation limit state, providing the same intensity level as that obtained from nonlinear analyses carried out on structural models with infills. Finally, the proposed procedures are applied to four-story and eight-story case study-infilled frames, designed for seismic loads according to current technical codes. The results of these application examples are presented and discussed. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The estimation of direct and indirect losses due to earthquakes is a key issue in the Performance Based Earthquake Engineering framework. In commonly adopted loss computation tools, no specific data related to masonry infill panels, widespread in moment-resisting-frame residential buildings, are available to perform a probabilistic assessment of losses. To fill this gap, specific fragility and loss functions have been recently proposed in the last years. To assess their validity and estimate the relevance of the repair costs due to infills after earthquakes with respect to the total reconstruction process, the present work analyses the Reinforced Concrete residential buildings with masonry infills struck by the 2009 L'Aquila (Italy) earthquake, focusing on the dataset of "lightly" damaged buildings, where only damage to masonry infills occurred. Based on available data related to these buildings, the observed damage scenario after L'Aquila earthquake is first obtained. The repair costs for infills are estimated given this damage scenario. The resulting estimated repair costs are then compared with the actual repair costs presented in the available literature. The percentage influence of infills on the total repair costs due to earthquakes for residential buildings is lastly computed, resulting on average equal to the fifty percent. [ABSTRACT FROM AUTHOR]