1,216 research outputs found
Optimal Dislocation of Branch Offices From View of Transport Availability
No full textThe district authorities were canceled and substituted by self-governments branch offices after the public administration reform in the Czech Republic. So-called municipalities with extended sphere of authority were proposed for placing of branch offices. These branch offices were chosen regardless of their transport availability. The article deals with the problem of determination of optimal number of branch offices and of their attract areas, from view of their transport availability. The problem is solved with the methods of mathematical programming. The problem was by the help of Lagrange multiplicator converted to incapacitated location problem with criterion function sum(fyi)+sum sum (cij xij) where xij is arbitrary variable expressing whether the municipality j is allocated to the branch office i, cij is a coefficient representing distance from branch office i, weighted with population of the municipality j, yi is bivalent variable expressing whether in the municipality will be established the branch office and f is constant presenting branch office establishment costs. Model is solved with Erlenkotter method realized by the help of BB dual algorithm.
Does Fluoroquinolones and Third-Generation Cephalosporins Restriction Reverse Extended-Spectrum β-Lactamases Klebsiella pneumoniae Resistance Rates?
No full textAim: To decrease the incidence and resistance rates of extended-spectrum β-lactamases (ESBL) Klebsiella pneumoniae (KP) by restriction of the use of third-generation cephalosporins (3GCs) and fluoroquinolones. Methods: Consumption of 3GCs, fluoroquinolones, and carbapenems in association with ertapenem and fluoroquinolone-resistant KP isolates, were analyzed in 21 months by autoregressive integrated moving average models. A follow-up analysis was performed 5 years later. Results: Consumption of 3GCs decreased significantly during the postintervention period. Their restriction was associated with a decrease in ertapenem-resistant KP isolates by 17.5%. Fluoroquinolone, 3GCs, and carbapenem use did not significantly predict the percentage of ertapenem-resistant KP isolates. Fluoroquinolone, but not cephalosporin use, significantly predicted the percentage of fluoroquinolone-resistant isolates, with an increase of 1 defined daily dose (DDD) of fluoroquinolone/100 occupied bed-days (OBDs) corresponding to a 0.32% increase of fluoroquinolone-resistant isolates (p = 0.008). A decrease of 1 DDD of carbapenem/100 OBD was associated with a 16.94% increase of fluoroquinolone-resistant isolates (p = 0.007). Five years later, the consumption of all three antimicrobial classes increased significantly compared with the 2011-2013 period, whereas ertapenem-resistant KP rates significantly decreased. Conclusion: This study may bring a valuable contribution to the understanding of the intricate association between antibiotic consumption and bacterial resistance. Reporting a spectrum of different results could present a useful basis for more profound research of various interventions' effects
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
Preparation of Thiol Conjugates of the Mycotoxin Deoxynivalenol and their Occurrence in Nature
No full textCereal crops (such as oats, wheat, barley, rye, corn etc.) are often contaminated with toxigenic fungi during field or storage conditions, which can consequently lead to food and feed contamination with mycotoxins and to crop losses. One of the most common and worldwide occurring genera of fungi infecting crops is Fusarium, including species that may produce mycotoxins like trichothecenes, fumonisins and zearalenone. Trichothecenes inhibit protein synthesis by binding to the ribosomes. Based on their chemical structure, they are further divided into Type A, B, C and D. The Type B trichothecenes, characterized by the presence of a carbonyl group at the C-8 position, is not the most acutely toxic subgroup, but it is the most prevalent in North America and Europe. The economically most relevant mycotoxin, belonging to the Type B group of trichothecenes, is 4-deoxynivalenol (DON). It contains several structural features that enable plants or animals to biotransform the molecule, thereby decreasing or eliminating its toxicity. These features are an epoxy ring, hydroxyl groups and an α,β-unsaturated carbonyl group. Some of the plant biotransformation products of DON (e.g. deoxynivalenol 3-β-Dglucoside) are well known and characterized. More recent studies used carbon isotope labelled DON in metabolomic studies in wheat and tentatively identified new conjugates such as DON–glutathione (DON–GSH), DON–cysteinylglycine (DON–CysGly) and DON–cysteine (DON–Cys). As the thiol addition may either occur irreversibly on the 12,13-epoxide group of DON or reversibly at the 9,10-conjugated double bond, it was necessary to synthesize these conjugates in order to identify the biotransformation products in real samples.
The main focus of this work was to get insight into the reaction between DON and different thiols, including biologically significant compounds as L-cysteine and L-glutathione. The reaction between the model thiol 2-mercaptoethanol and DON was initially used to optimize the reaction conditions and to develop a liquid chromatography–mass spectrometry (LC–MS) method to follow the reaction and to analyze the products. The reactions were tested in a pH range of 7.3–10.7, and with several thiols (2-aminoethane thiol, sodium methanethiolate, sodium 2-mercaptoethanesulfonate, L–cysteine and L–glutathione). The pattern in the LC–MS chromatograms of the reaction between DON and tested thiols was similar – what was shown to be the C-13 (epoxide) conjugate was always the earliest eluting peak, while there were several C- 10 (Michael) adducts that were isomerizing and their ratios changing with time. The reactions occurred fastest under the basic conditions, but also occurred at physiological pH. The reaction was also carried out between 2-mercaptoethanol and trichothecenes that differentiate from DON in a way that is significant to prove the binding position of a thiol, such as T-2 tetraol that has hydroxyl group at C-8 and therefore lacking a conjugated double bond, and deepoxy-DON that contains reduced 12,13-epoxy ring. A DON-13-mercaptoethanol and 10,13-double adduct was purified and characterized using nuclear magnetic resonance (NMR). Once major reaction products were characterized, optimized conditions (basic pH and thiol excess) were applied and used to synthesize and purify epoxide and thermodynamically favored Michael adducts of DON–GSH and DON–Cys conjugates. In order to prepare analytical standards, conjugates were quantified using qNMR (ERETIC2). The effect of the synthesized conjugates (DON-13-mercaptoethanol, DON-10,13-dimercaptoethanol, DON-10-Cys and DON-13-Cys) on cell proliferation and metabolic activity, as well as the expression of proinflammatory cytokines was tested. All of the tested compounds displayed significantly lower toxicity in vitro compared to DON.
The reaction mixtures containing DON and two dipeptides, CysGly and γ-GluCys, and Nacetylcysteine (NAC) were also prepared and followed over time for the comparative analysis of real samples and together with the obtained standards were used in the analysis of oats and spring wheat samples from Norway that were naturally contaminated with DON and in an extract of wheat spikelets that were artificially treated with DON. The LC–HRMS analysis showed that the main products of the artificially contaminated wheat were C-10 conjugates of DON and GSH, Cys and CysGly, while the naturally contaminated wheat and oat samples contained predominantly C-13-linked conjugates with GSH, Cys, CysGly and NAC
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
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
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
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
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
Enacting Reasoning-and-Proving in Secondary Mathematics Classrooms through Tasks
No full textProof is the mathematical way of convincing oneself and others of the truth of a claim for all cases in the domain under consideration. As such, reasoning-and-proving is a crucial, formative practice for all students in kindergarten through twelfth grade, which is reflected in the Common Core State Standards in Mathematics. However, students and teachers exhibit many difficulties employing, writing, and understanding reasoning-and-proving. In particular, teachers are challenged by their knowledge base, insufficient resources, and unsupportive pedagogy.
The Cases of Reasoning and Proving (CORP) materials were designed to offer teachers opportunities to engage in reasoning-and-proving tasks, discuss samples of authentic practice, examine research-based frameworks, and develop criteria for evaluating reasoning-and-proving products based on the core elements of proof. A six-week graduate level course was taught with the CORP materials with the goal of developing teachers’ understanding of what constitutes reasoning-and-proving, how secondary students benefit from reasoning-and-proving, and how they can support the development of students’ capacities to reason-and-prove. Research was conducted on four participants of the course during either their first or second year of teaching. The purpose of the research was to study the extent to which the participants selected, implemented, and evaluated students’ work on reasoning-and-proving tasks. The participants’ abilities were examined through an analysis of answers to interview questions, tasks used in class, and samples of student work, and scoring criteria. The results suggest that: 1.) participants were able to overcome some of the limitations of their insufficient resource by modifying and creating some reasoning-and-proving exercises; 2.) participants were able to maintain the level of cognitive demand of proof tasks during implementation; and 3) participants included some if not all of the core elements of proof in their definition of proof and in their evaluation criteria for student products of reasoning-and-proving products
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