108 research outputs found
NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features
No full textThe role of autoimmunity in central nervous system (CNS) disorders is rapidly expanding. In the last twenty years, different types of autoantibodies targeting subunits of ionotropic glutamate receptors have been found in a variety of patients affected by brain disorders. Several of these antibodies are directed against NMDA receptors (NMDAR), mostly in autoimmune encephalitis, whereas a growing field of research has identified antibodies against AMPA receptor (AMPAR) subunits in patients with different types of epilepsy or frontotemporal dementia. Several in vitro and in vivo studies performed in the last decade have dramatically improved our understanding of the molecular and functional effects induced by both NMDAR and AMPAR autoantibodies at the excitatory glutamatergic synapse and, consequently, their possible role in the onset of clinical symptoms. In particular, the method by which autoantibodies can modulate the localization at synapses of specific target subunits leading to functional impairments and behavioral alterations has been well addressed in animal studies. Overall, these preclinical studies have opened new avenues for the development of novel pharmacological treatments specifically targeting the synaptic activation of ionotropic glutamate receptors
Rabphilin-3A Drives Structural Modifications of Dendritic Spines Induced by Long-Term Potentiation
No full textThe interaction of Rabphilin-3A (Rph3A) with the NMDA receptor (NMDAR) in hippocampal neurons plays a pivotal role in the synaptic retention of this receptor. The formation of a Rph3A/NMDAR complex is needed for the induction of long-term potentiation and NMDAR-dependent hippocampal behaviors, such as spatial learning. Moreover, Rph3A can also interact with AMPA receptors (AMPARs) through the formation of a complex with myosin Va. Here, we used a confocal imaging approach to show that Rph3A overexpression in primary hippocampal neuronal cultures is sufficient to promote increased dendritic spine density. This morphological event is correlated with an increase in GluN2A-containing NMDARs at synaptic membranes and a decrease in the surface levels of GluA1-containing AMPARs. These molecular and morphological modifications of dendritic spines are sufficient to occlude the spine formation induced by long-term potentiation, but do not prevent the spine loss induced by long-term depression. Overall, our results demonstrate a key role for Rph3A in the modulation of structural synaptic plasticity at hippocampal synapses that correlates with its interactions with both NMDARs and AMPARs
Assessment Methods for Structural and Hydraulic Properties of Concrete Sewer Pipes
No full textAsset management is a tool for maintaining the required level of serviceability of urban drainage systems, which are costly to construct and in some cases even more costly to replace. The required asset management effort to achieve a certain level of service is unclear due to a limited knowledge on sewer failure mechanisms and due to scarcity of information on the functioning and conditions of urban drainage systems. An important question is: what information of what quality is necessary for cost-effective sewer asset management? In The Netherlands the majority of urban drainage systems are made of concrete elements (about 72%), including nearly all main sewers > 500 mm, thus making the information on the concrete sewer pipes of significant importance. This research aims at (i) identifying the required information on the structural and hydraulic performance of the sewer pipes, (ii) quantifying the uncertainties of information and (iii) improving the quality of this information in order to further understand the changes in processes/status. Sewer failure mechanisms explain the structural and/or operational failures of sewer elements. In order to be able to identify the main processes and defects responsible for the structural and/or operational failures of sewer elements, as well as the possibility of obtaining the information about them, a HAZard and Operability (HAZOP) approach was applied. This technique was demonstrated to be applicable for analysing the information needed for sewer asset management. Structural strength and hydraulic capacity are two essential parameters in the assessment of the need for sewer rehabilitation. In sewer systems where corrosion is the dominant failure mechanism, visual inspection by closed circuit television (CCTV) and core sampling are among the methods mostly applied to assess sewer pipe condition. A study was carried out on visual inspection and drill core analysis in order to enhance a further understanding of the limitations and potentials of both methods and the added value of combining the information from both sources. Both methods have been applied on a selected sewer reach in the city of The Hague, which was reportedly subject to pipe corrosion. The results show that both methods, visual inspection and core sampling, are associated with large uncertainties and that there is no obvious correlation between the results of visual inspection and the results of drill core analysis. The conclusion is that information of a certain quality (depending on the circumstances) on the actual status of the assets is a prerequisite for adequate sewer asset management. For instance, especially concrete pipes suffer from loss of wall thickness due to biochemical corrosion and, consequently, a decreasing structural strength along with an increase in hydraulic roughness. Unfortunately, routinely used visual inspection methods do not allow a quantification of the internal pipe geometry, which would enable not only detection but also the quantification of the progress of biochemical corrosion. Advances in laser technology and digital cameras theoretically allow a cost-effective application of laser profilers to measure the interior geometry of sewer pipes. An analysis of associated uncertainties revealed that the position and alignment of the laser in commonly used laser profiling techniques are the main sources of measurement errors. A full-scale laboratory set-up demonstrated, based on tests on a new and an 89 year old corroded sewer pipe, that laser profiling is indeed capable of measuring the interior geometry accurately enough to determine wall thickness losses for corroded pipes, provided that the position and alignment of the laser and camera are accounted for. Further, drill core samples are taken for an analysis of the material characteristics of concrete pipes in order to improve the quality of decision making on rehabilitation actions. It was shown in this study that core sampling is associated with a significant uncertainty. The results of core samples are compared with the results of full-scale pipe cracking lab experiments. It is shown that the concrete of deteriorated sewer pipes shows a significant variability in material characteristics. Further it is shown that the formation of ettringite due to biochemical sulphuric corrosion is not necessarily limited to the crown of the pipe and that also degradation of pipe material, measured by the carbonation depth, is occurring at the inside and outside of the pipe. It is concluded that tensile splitting strength and carbonation depth (i.e. loss of 'healthy' wall thickness) are material property parameters of core sampling with a sufficiently high correlation (R^2 > 0.90) with the constructive strength of the pipe. The thickness of the remaining healthy concrete material is the optimal parameter in terms of correlation with collapse strength, as this requires the smallest sampling size. Furthermore, in sewer asset management, decision making on rehabilitation or replacement should preferably be based on the actual functionality of a sewer system. In order to judge the ability of a sewer system to transport sewage, hydrodynamic models are used: hydraulic roughness is one of the key parameters. For new pipes, the hydraulic properties are well known, but for aged pipes, with uneven deterioration along the cross section, information on the hydraulic roughness is lacking. The potential of laser profiling methods for accurate, non-invasive and non-intrusive assessment of the hydraulic roughness of concrete sewer pipes is described, demonstrated and discussed. Processing of raw scanned data consists of two steps: (i) spatial interpolation with uncertainty analysis and (ii) statistical analysis for estimating the hydraulic roughness. Moreover, a statistical analysis was carried out to determine the minimal scanning resolution required in order to yield results accurate enough for subsequent modelling uses. The results show a promising potential of the laser scanning approach for a simple and fast quantification of the hydraulic roughness in a sewer system. A Prototype v1.0 (in this study) of an unbiased laser profiler was developed to improve the accuracy of collected information. However, there is a need for more accurate apparatus. The new design of the Prototype v2.0 presented provides accurate measurements (sigma < 2 mm) of the cross section and, from frame to frame, an accurate 3D image of a pipe. The potential applications of the improved laser profiling technique are comprehensive e.g. enhancement of inaccurate visual inspection, deposit measurements, roughness measurements. The combination of the two methods, i.e. to use the laser profiler to determine the pipe interior geometry as well as to identify representative patches where roughness should be measured, is an opportunity to strengthen laser profiling as a method that may partially replace a CCTV inspection as a dominantly applied sewer investigation technique. Additionally to achieve a higher accuracy, there are several improvements that can be applied to a potential third version of the prototype. Currently the amount of raw data that is generated during the experiment over 1 m of pipe length is around 4.86 GB: the data flow is too high for an embedded application but this can be significantly reduced. There are still some improvements to be done with the presented hardware to make the data acquisition faster and easier. Future work will concentrate on the development and improvement of the laser profiling technique accuracy and possibilities for its use - Prototype v3.0. The results of this research will be used for future development of inspection strategies using core sampling. For sewer rehabilitation decisions, it is necessary to be able to calculate the remaining strength of the soil-pipe construction environment for deteriorated pipes. Further research will concentrate on simulations with a Finite Element Method (FEM), with the pipe geometry information provided by laser profiling and material properties by core sampling. The model will be used to determine the remaining load-bearing capacity of a sewer pipe and to determine the type of information needed to further enhance the decision making process.Water ManagementCivil Engineering and Geoscience
From star‐forming spirals to passive spheroids: integral field spectroscopy of E+A galaxies
No full textWe present three‐dimensional spectroscopy of 11 E+A galaxies at z = 0.06–0.12. These galaxies were selected for their strong Hδ absorption but weak (or non‐existent) [O ii ] λ3727 and Hα emission. This selection suggests that a recent burst of star formation was triggered but subsequently abruptly ended. We probe the spatial and spectral properties of both the young (≲1 Gyr) and old (≳few Gyr) stellar populations. Using the Hδ equivalent widths we estimate that the burst masses must have been at least 10 per cent by mass ( M burst ≳ 10 10 M ⊙ ), which is also consistent with the star formation history inferred from the broad‐band spectral energy distributions. On average the A stars cover ∼33 per cent of the galaxy image, extending over 2–15 kpc 2 , indicating that the characteristic E+A signature is a property of the galaxy as a whole and not due to a heterogeneous mixture of populations. In approximately half of the sample, we find that the A stars, nebular emission and continuum emission are not co‐located, suggesting that the newest stars are forming in a different place than those that formed ≲1 Gyr ago, and that recent star formation has occurred in regions distinct from the oldest stellar populations. At least 10 of the galaxies (91 per cent) have dynamics that class them as ‘fast rotators’ with magnitudes, v /σ, λ R and bulge‐to‐total (B/T) ratio comparable to local, representative ellipticals and S0s. We also find a correlation between the spatial extent of the A stars and the dynamical state of the galaxy such that the fastest rotators tend to have the most compact A star populations, providing new constraints on models that aim to explain the transformation of later type galaxies into early types. Finally, we show that there are no obvious differences between the line extents and kinematics of E+A galaxies detected in the radio (active galactic nucleus, AGN) compared to non‐radio sources, suggesting that AGN feedback does not play a dramatic role in defining their properties, and/or that its effects are short.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90164/1/j.1365-2966.2011.20082.x.pd
Assessing the quality of sewer pipes
No full textSewerage and urban drainage systems are capital intensive infrastructures characterised by process and structure complexity. For instance, in the Netherlands (2009), the municipalities spent around \u801,2 billion on sewerage (or \u80151/per household/annum) (Walder, 2011). Proper operation and maintenance of such systems together with rehabilitation will ensure long life of the infrastructures while meeting serviceability requirements. Therefore, insight in the actual status of the assets is a prerequisite for adequate sewer asset management.Water ManagementCivil Engineering and Geoscience
GluA3 autoantibodies induce alterations in dendritic spine and behavior in mice
No full textAutoantibodies targeting the GluA3 subunit of AMPA receptors (AMPARs) have been found in patients with Rasmussen's encephalitis and different types of epilepsy and were associated with the presence of learning and attention deficits. Our group recently identified the presence of anti-GluA3 immunoglobulin G (IgG) in about 25% of patients with frontotemporal dementia (FTD), thus suggesting a novel pathogenetic role also in chronic neurodegenerative diseases. However, the in vivo behavioral, molecular and morphological effects induced these antibodies are still unexplored. We injected anti-GluA3 IgG purified from the serum of FTD patients, or control IgG, in mice by intracerebroventricular infusion. Biochemical analyses showed a reduction of synaptic levels of GluA3-containing AMPARs in the prefrontal cortex (PFC), and not in the hippocampus. Accordingly, animals injected with anti-GluA3 IgG showed significant changes in recognition memory and impairments in social behavior and in social cognitive functions. As visualized by confocal imaging, functional outcomes were paralleled by profound alterations of dendritic spine morphology in the PFC. All observed behavioral, molecular and morphological alterations were transient and not detected 10-14 days from anti-GluA3 IgG injection. Overall, our in vivo preclinical data provide novel insights into autoimmune encephalitis associated with anti-GluA3 IgG and indicate an additional pathological mechanism affecting the excitatory synapses in FTD patients carrying anti-GluA3 IgG that could contribute to clinical symptoms
Potential of Laser Scanning for Quantification of Sediment Deposits in Sewer
No full textThere is still a long way to go in understanding the behaviour of solids in sewers due to the difficulties in obtaining sufficient monitoring data to be able to understand the dominant processes. Laser profilers have shown to be capable of measuring the pipe interior, with a high accuracy, which is sufficient to be able to detect and quantify wall losses. This paper describes the potential of laser scanning for measuring sediment volumes in sewers. In addition, the propagation of uncertainties from laser measurements to sediment volumes are discussed, with special attention to conditions that could affect the measurements. The Laser profiler has shown to be capable of measuring the pipe interior, which is sufficient to be able to detect and quantify sediment volume. Overall, this research is a first step in defining a new inspection concept that will be able to give reliable information on relevant failure mechanisms.Water ManagementCivil Engineering and Geoscience
Identificatie van de benodigde informatie voor het beoordelen van faalmechanismen bij het rioleringsbeheer
No full textRioleringsbeheer is een eerste vereiste om het gewenste niveau van functioneren van de riolering te behouden. Welke inspanning op het gebied van rioleringsbeheer nodig is om een bepaald niveau van functioneren te bereiken is onduidelijk, omdat zowel de processen in als de structuur van de rioolstelsels complex zijn. Een belangrijke vraag hierbij is welke informatie er nodig is en hoe deze informatie verkregen moet worden. Faaimechanismen van het rioolsysteem verklaren het structurele en operationele falen van onderdelen van het rioolsysteem. Deze studie richt zich op het vaststellen welke informatie er nodig is om faalmechanismen in de riolering op te sporen en te identificeren. Om het identificeren van de faalmechanismen mogelijk te maken, is gebruik gemaakt van de zogenaamde HAZOP (Hazard+OPerability) benadering. De belangrijkste processen en tekortkomingen verantwoordelijk voor het structurele en/of operationele falen van rioleringsonderdelen zijn geïdentificeerd, evenab de mogelijkheden om de ervoor benodigde informatie te verkrijgen. Deze informatie is nodig om de kans op een faalgebeurtenis te kunnen schatten en is uiteindelijk ook nodig om vast te stellen welke informatie nodig is voor goed functioneren van het systeem.Water ManagementCivil Engineering and Geoscience
Identification of the information needs for sewer asset management by assessing failure mechanics
No full textAsset management is a prerequisite for maintaining the required level of serviceability of urban drainage systems. The required asset management effort to achieve a certain level of service is unclear due to sewer systems process and structure complexity. One of the main questions of asset management is what kind of information is needed, and how this information can be obtained. Sewer failure mechanisms explain the structural/operational failures of sewer elements. This study focuses on determining the information required to be able to detect and identify sewer failure mechanisms. In order to be able to identify the failure mechanisms involved, a HAZOP approach was applied. The main processes and defects responsible for the structural/operational failures of sewer elements were identified, as well as possibility of obtaining the information about them. This information will help in estimating the probability of failure occurrence and generally it will help defining the information needed for proper serviceability.Water ManagementCivil Engineering and Geoscience
Family law aspect of biomedically assisted conception in Serbian and European law
No full textFree access to biomedically assisted conception for the couples of less than 40 years of age has been introduced in Serbia recently, while in 2009 the Act on curing infertility by biomedically assisted conception was adopted. In this paper the following issues are discussed: notion of biomedically assisted conception, participants in the process, donors, motherhood and fatherhood, status of spare embryos. The author concludes that even though Serbia is one of the last European countries to adopt the Act on biomedically assisted conception and there was an opportunity to use the experiences of other countries in this field and to adopt an act which would be theoretically meaningful and clear, unfortunately this opportunity was not taken. The author expresses hope that the Act would be changed in a near future, in order to clear the lack of clarity and contradictions and harmonize legal solutions with theoretical legal principles in this field. In this paper the author uses comparative method comparing Serbian legislation and legislation of different European countries. .</jats:p
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