bluuebunny/crossref_metadata_2025 huggingface dataset:
Achievements and Challenges in Machine Vision-Based Inspection of Large Concrete Structures
Authors: Koch C. , Paal S. German , Rashidi A. , Zhu Z. , König M. , Brilakis I.
Published: April 2014

Large concrete structures need to be inspected in order to assess their current physical and functional state, to predict future conditions, to support investment planning and decision making, and to allocate limited maintenance and rehabilitation resources. Current procedures in condition and safety assessment of large concrete structures are performed manually leading to subjective and unreliable results, costly and time-consuming data collection, and safety issues. To address these limitations, automated machine vision-based inspection procedures have increasingly been proposed by the research community. This paper presents current achievements and open challenges in vision-based inspection of large concrete structures. First, the general concept of Building Information Modeling is introduced. Then, vision-based 3D reconstruction and as-built spatial modeling of concrete civil infrastructure are presented. Following that, the focus is set on structural member recognition as well as on concrete damage detection and assessment exemplified for concrete columns. Although some challenges are still under investigation, it can be concluded that vision-based inspection methods have significantly improved over the last 10 years, and now, as-built spatial modeling as well as damage detection and assessment of large concrete structures have the potential to be fully automated.
Effects of Wireless Sensor Network Uncertainties on Output-Only Modal Analysis Employing Merged Data of Multiple Tests
Authors: Nguyen T. , Chan T.H.T. , Thambiratnam D.P.
Published: April 2014

The use of Wireless Sensor Networks (WSNs) for vibration-based Structural Health Monitoring (SHM) has become a promising approach due to many advantages such as low cost, fast and flexible deployment. However, inherent technical issues such as data asynchronicity and data loss have prevented these distinct systems from being extensively used. Recently, several SHM-oriented WSNs have been proposed and believed to be able to overcome a large number of technical uncertainties. Nevertheless, there is limited research verifying the applicability of those WSNs with respect to demanding SHM applications like modal analysis and damage identification. Based on a brief review, this paper first reveals that Data Synchronization Error (DSE) is the most inherent factor amongst uncertainties of SHM-oriented WSNs. Effects of this factor are then investigated on outcomes and performance of the most robust Output-only Modal Analysis (OMA) techniques when merging data from multiple sensor setups. The two OMA families selected for this investigation are Frequency Domain Decomposition (FDD) and data-driven Stochastic Subspace Identification (SSI-data) due to the fact that they both have been widely applied in the past decade. Accelerations collected by a wired sensory system on a large-scale laboratory bridge model are initially used as benchmark data after being added with a certain level of noise to account for the higher presence of this factor in SHM-oriented WSNs. From this source, a large number of simulations have been made to generate multiple DSE-corrupted datasets to facilitate statistical analyses. The results of this study show the robustness of FDD and the precautions needed for SSI-data family when dealing with DSE at a relaxed level. Finally, the combination of preferred OMA techniques and the use of the channel projection for the time-domain OMA technique to cope with DSE are recommended.
Experimental Study on Failure Mechanism of RC Walls with Different Boundary Elements under Vertical and Lateral Loads
Authors: Zhang H.M. , Lu X.L. , Duan Y.F. , Zhu Y.
Published: April 2014

Reinforced concrete (RC) shear walls have been widely applied in high-rise buildings. DBSD (Displacement-Based Seismic Design) of shear wall structures requires more accurate deformation evaluation theories and methods. Boundary elements of RC walls have been found to have a significant impact on the seismic behaviours, but the strain-stress development details including plane section assumption and linear curvature distribution are seldom investigated by specialized experiments. To investigate the failure mechanism of shear walls and the influence of the boundary element, 6 RC wall specimens with different boundary elements are studied in this paper. Strain development data of the shear wall section and along wall height were collected during the loading procedure. The failure mechanism of the RC walls with different boundary elements is studied by discussing the development of the strain. Study emphasis is laid on the adaption of plane-section assumption during the whole service procedure, the curvature development along the wall height during the whole service procedure, the influence of boundary element to moment-curvature relationship. Test results indicate that boundary element can restrain the growth of the strain, enhance the horizontal bearing capacity, and improve the seismic resistant capacity. The study also re-evaluates the plane section assumption and linear curvature distribution currently used based on the results of the deformation of the shear walls by the experimental investigation of the shear walls with different boundary element.
Passive Hybrid System for Seismic Failure Mode Improvement of a Long-Span Cable-Stayed Bridges in the Transverse Direction
Authors: Xie Wen , Sun Limin
Published: April 2014

This paper presents a numerical study on the seismic damages and failure modes of a trial designed cable-stayed bridge (CSB) with a central span of 1,400 m under earthquake excitations. A passive hybrid control system is proposed to mitigate the seismic damage and improve the failure mode of the CSB; this is composed of a passive control system and several supplemental nonstructural links used as sacrificial energy dissipation devices. The passive control system, including conventional viscous fluid dampers (VFDs), is presented for comparison with the hybrid system. The results show that the top and bottom regions of the tower are simultaneously subjected to severe damage under extreme ground motion, indicating that the tower experiences an unexpected failure mode with double plastic hinges, whereas the piers experience a typical flexural failure mode, with only one plastic hinge concentrated at the bottom region of the pier in the transverse direction. The effects of the proposed passive hybrid control system on seismic damage control are superior to those of the passive control system with VFDs. As a result, the passive hybrid control strategy can successfully control seismic damage and effectively improve the failure mode of the CSB so that its seismic performance meets damage control targets based on seismic damage criteria.
An Artificial Neural Network Based Method for Seismic Fragility Analysis of Highway Bridges
Authors: Pang Yutao , Dang Xinzhi , Yuan Wancheng
Published: April 2014

Fragility functions have become widely adopted in the seismic risk assessment of highway bridges, or even a transportation network. The computational effort required for a fragility analysis of highway bridges using incremental dynamic analysis (IDA) can become excessive, far beyond the capability of modern computing systems, especially when dealing with the structural parameter uncertainty in generating the fragility functions. In this paper, an artificial neural network (ANN) based prediction scheme for the generation of analytical fragility curves for highway bridges is presented. And the extremely time-consuming process in traditional analytical fragility methodologies is replaced by properly trained ANNs. The implementation of ANNs is focused on the simulation of median value and standard deviation of IDA curves at a given intensity level. The uniform design method (UDM) is proposed for selecting the training datasets for establishing a well-trained ANN model. It is observed that the proposed procedure can provides accurate estimates of fragility curves with relative short time compared to conventional procedures. The sensitivity study also reveals importance of material or geometric uncertainty in developing fragility curves of highway bridges.
Comparison of Source Reconstruction Methods for Hybrid Aeroacoustic Predictions
Authors: Geiser Georg , Marinc Daniel , Schröder Wolfgang
Published: April 2014

Hybrid aeroacoustic prediction methods have gained increasing popularity to overcome the large differences between the fluid mechanics and acoustics length scales when noise generated by subsonic flows is investigated. The overall solution of those predictions essentially depends on the accurate representation of the acoustic sources leading to noise emissions. The sources are not generally known, since they are coupled to the turbulent dynamics of the fluid. A common approach is to determine the sources using computational fluid dynamics on a small domain of interest and to compute by an acoustic model the sound field on a larger domain. This coupling is susceptible since usually an interpolation in time is conducted to reduce the amount of data required for a proper source representation. The question of the impact of the interpolation on the acoustic solution arises or in other words, what interpolation formulation is necessary to not impact the acoustic result. Therefore, in this study, the quality of several time-interpolation methods is assessed to determine an appropriate acoustic source reconstruction. First, a general framework to design interpolating filters is presented that allows to obtain interpolation results of arbitrary order and differentiability and offers a configurable passband optimization. Several interpolators are evaluated in detail with special care for proper acoustic source reconstruction. The application to a subsonic turbulent plane jet at Reynolds number Re = 2000 reveals a better source representation by constrained broadband optimized interpolation. Least-squares optimized C0-interpolators with additional Taylor constraints according to the order of the time integration method showed the best result. A broadband error reduction turned out to be more important for the source reconstruction when compared to a strict order of convergence. The Taylor order of the interpolator, however, should be at least the Taylor order of the temporal integrator to achieve the desired convergence of the overall solution scheme. Hermitian interpolation was found to be too error-prone to inaccuracies in the numerical approximation of the required temporal derivatives, even though having the theoretical benefit of C1-differentiability of the interpolation result.
A Thousand Bim: A Rapid Value-Simulation Approach to Developing a BIM Tool for Supporting Collaboration during Schematic Design
Authors: Park Ju Hong , Nagakura Takehiko
Published: April 2014

The purpose of this study is to develop a BIM-based plug-in that is able to assist a collaboration among heterogeneous professionals. The tool will enable them to communicate in the same language, articulate criteria and priorities in multiple perspectives, and to share rapidly simulated evaluations of schematic design variations. Among many barriers that block collaborations among professionals, a quintessential barrier in the building and design industries may be epistemological rather than physical. The professionally different ways of thinking, expertise, values, and priorities can be a block on the collaborative development process of architectural design projects. This paper takes the example of the relationship between developers and architects, who tend to have different evaluation criteria. A real-time value simulation tool is introduced as a means to generate possible building typologies on a given project site, with computation of expected total values expressed in simple financial terms.
Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNALeu(UUR) and tRNALys
Authors: Leszczynska Grazyna , Leonczak Piotr , Wozniak Karolina , Malkiewicz Andrzej
Published: April 2014

5-Taurinomethyluridine (τm5U) and 5-taurinomethyl-2-thiouridine (τm5s2U) are located at the wobble position of human mitochondrial (hmt) tRNALeu(UUR) and tRNALys, respectively. Both hypermodified units restrict decoding of the third codon letter to A and G. Pathogenic mutations in the genes encoding hmt-tRNALeu(UUR) and hmt-tRNALys are responsible for the loss of the discussed modifications and, as a consequence, for the occurrence of severe mitochondrial dysfunctions (MELAS, MERRF). Synthetic oligoribonucleotides bearing modified nucleosides are a versatile tool for studying mechanisms of genetic message translation and accompanying pathologies at nucleoside resolution. In this paper, we present site-specific chemical incorporation of τm5U and τm5s2U into 17-mers related to the sequence of the anticodon arms hmt-tRNALeu(UUR) and hmt-tRNALys, respectively employing phosphoramidite chemistry on CPG support. Selected protecting groups for the sulfonic acid (4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutyl) and the exoamine function (-C(O)CF3) are compatible with the blockage of the canonical monomeric units. The synthesis of τm5s2U-modified RNA fragment was performed under conditions eliminating the formation of side products of 2-thiocarbonyl group oxidation and/or oxidative desulphurization. The structure of the final oligomers was confirmed by mass spectroscopy and enzymatic cleavage data.
Derivation and characterization of Dicer- and microRNA-deficient human cells
Authors: Bogerd Hal P. , Whisnant Adam W. , Kennedy Edward M. , Flores Omar , Cullen Bryan R.
Published: April 2014

We have used genome editing to generate inactivating deletion mutations in all three copies of the dicer (hdcr) gene present in the human cell line 293T. As previously shown in murine ES cells lacking Dicer function, hDcr-deficient 293T cells are severely impaired for the production of mature microRNAs (miRNAs). Nevertheless, RNA-induced silencing complexes (RISCs) present in these hDcr-deficient cells are readily programmed by transfected, synthetic miRNA duplexes to repress mRNAs bearing either fully or partially complementary targets, including targets bearing incomplete seed homology to the introduced miRNA. Using these hDcr-deficient 293T cells, we demonstrate that human pre-miRNA processing can be effectively rescued by ectopic expression of the Drosophila Dicer 1 protein, but only in the presence of the PB isoform of Loquacious (Loqs-PB), the fly homolog of the hDcr cofactor TRBP. In contrast, Drosophila Dicer 2, even in the presence of its cofactors Loqs-PD and R2D2, was unable to support human pre-miRNA processing. Interestingly, although ectopic Drosophila Dicer 1/Loqs-PB or hDcr both rescued pre-miRNA processing effectively in these hDcr-deficient cells, there were significant differences in the ratio of the miRNA isoforms that were produced, especially in the case of miR-30 family members, and we also noted differences in the relative expression level of miRNAs vs. passenger strands for a subset of human miRNAs. These data demonstrate that the mechanisms underlying the accurate processing of pre-miRNAs are largely, but not entirely, conserved between mammalian and insect cells.
The MID-PIWI module of Piwi proteins specifies nucleotide- and strand-biases of piRNAs
Authors: Cora Elisa , Pandey Radha R. , Xiol Jordi , Taylor Josh , Sachidanandam Ravi , McCarthy Andrew A. , Pillai Ramesh S.
Published: April 2014

Piwi-interacting RNAs (piRNAs) guide Piwi Argonautes to suppress transposon activity in animal gonads. Known piRNA populations are extremely complex, with millions of individual sequences present in a single organism. Despite this complexity, specific Piwi proteins incorporate piRNAs with distinct nucleotide- and transposon strand-biases (antisense or sense) of unknown origin. Here, we examined the contribution of structural domains in Piwi proteins toward defining these biases. We report the first crystal structure of the MID domain from a Piwi Argonaute and use docking experiments to show its ability to specify recognition of 5′ uridine (1U-bias) of piRNAs. Mutational analyses reveal the importance of 5′ end-recognition within the MID domain for piRNA biogenesis in vivo. Finally, domain-swapping experiments uncover an unexpected role for the MID-PIWI module of a Piwi protein in dictating the transposon strand-orientation of its bound piRNAs. Our work identifies structural features that allow distinguishing individual Piwi members during piRNA biogenesis.
A Zig-Zag Approach for Competitive Group Testing
Authors: Cheng Yongxi , Du Ding-Zhu , Xu Yinfeng
Published: April 2014

In many fault-detection problems, we want to identify defective items from a set of n items using the minimum number of tests. Group testing is a scenario in which each test is on a subset of items and determines whether the subset contains at least one defective item. In practice, the number d of defective items is often unknown in advance. In this paper, we present a new algorithm for the above group testing problem and prove that it has very good performance guarantee. More specifically, the number of tests used by the new algorithm is bounded from above by d log(n/d) + 3d + O(log2 d). The new algorithm is designed based on a zig-zag approach that has not been studied before and is intuitive and easy to implement. When 0 < d < ρ0n where ρ0 = 1 − 4/e2 = 0.45…, which holds for most practical applications, our new algorithm has better performance guarantee than any previous best result. Computational results show that the new algorithm has very good practical performances.
Estimating Demand for Mobile Applications in the New Economy
Authors: Ghose Anindya , Han Sang Pil
Published: April 2014

In 2013, the global mobile app market was estimated at over US$50 billion and is expected to grow to $150 billion in the next two years. In this paper, we build a structural econometric model to quantify the vibrant platform competition between mobile (smartphone and tablet) apps on the Apple iOS and Google Android platforms and estimate consumer preferences toward different mobile app characteristics. We find that app demand increases with the in-app purchase option wherein a user can complete transactions within the app. On the contrary, app demand decreases with the in-app advertisement option where consumers are shown ads while they are engaging with the app. The direct effects on app revenue from the inclusion of an in-app purchase option and an in-app advertisement option are equivalent to offering a 28% price discount and increasing the price by 8%, respectively. We also find that a price discount strategy results in a greater increase of app demand in Google Play compared with Apple App Store, and app developers can maximize their revenue by providing a 50% discount on their paid apps. Using the estimated demand function, we find that mobile apps have enhanced consumer surplus by approximately $33.6 billion annually in the United States, and we discuss various implications for mobile marketing analytics, app pricing, and app design strategies.

This paper was accepted by Alok Gupta, special issue on business analytics.
Combinatorial Benders' Cuts for the Strip Packing Problem
Authors: Côté Jean-François , Dell'Amico Mauro , Iori Manuel
Published: April 2014

We study the strip packing problem, in which a set of two-dimensional rectangular items has to be packed in a rectangular strip of fixed width and infinite height, with the aim of minimizing the height used. The problem is important because it models a large number of real-world applications, including cutting operations where stocks of materials such as paper or wood come in large rolls and have to be cut with minimum waste, scheduling problems in which tasks require a contiguous subset of identical resources, and container loading problems arising in the transportation of items that cannot be stacked one over the other.

The strip packing problem has been attacked in the literature with several heuristic and exact algorithms, nevertheless, benchmark instances of small size remain unsolved to proven optimality. In this paper we propose a new exact method that solves a large number of the open benchmark instances within a limited computational effort. Our method is based on a Benders' decomposition, in which in the master we cut items into unit-width slices and pack them contiguously in the strip, and in the slave we attempt to reconstruct the rectangular items by fixing the vertical positions of their unit-width slices. If the slave proves that the reconstruction of the items is not possible, then a cut is added to the master, and the algorithm is reiterated.

We show that both the master and the slave are strongly 𝒩𝒫-hard problems and solve them with tailored preprocessing, lower and upper bounding techniques, and exact algorithms. We also propose several new techniques to improve the standard Benders' cuts, using the so-called combinatorial Benders' cuts, and an additional lifting procedure. Extensive computational tests show that the proposed algorithm provides a substantial breakthrough with respect to previously published algorithms.
Vital Tooth Bleaching: A Case Report
Authors: Maiti Niladri , Das Utpal Kumar
Published: April 2014

A dazzling white smile has been a symbol of beauty, health and vitality for hundreds of years. Discolouration, especially when the front teeth are affected, means a significant disturbance of aesthetics and can decrease a patient’s self esteem. Public demand for aesthetic dentistry, including tooth whitening, has increased in recent years. Compared with restorative treatment modalities, whitening, also referred to as bleaching, is the most conservative treatment for discolored teeth. This public demand for a whiter smile and improved aesthetics has made tooth whitening a popular and often requested dental procedure, since it offers a conservative treatment option for discolored teeth. Whitening often enhances the treatment and encourages patients to seek further aesthetic treatment. Dental bleaching offers a conservative, simplified, and low cost approach to change the color of discoloured teeth. Current bleaching techniques include a dentist-prescribed in-office technique, an at-home applied technique, or a combination of both. The pigments oxidation is responsible for tooth bleaching and can be carried out with two different products; carbamide peroxide and hydrogen peroxide. This case report reflects the remarkable change of tooth color by in-office bleaching.
Amalgam Inlay- An Innovative Technique
Authors: Ballal Nidambur Vasudev , Bhat Kadengodlu Seetharama , Rathi Shubha , Saraswathi Vidya
Published: April 2014

Dental amalgam is the most thoroughly researched and tested restorative material, which has been used successfully in dentistry for more than a century. Despite its poor esthetic and lack of adhesion, it is still one of the most widely used restorative materials in dental practice. This case report describes a novel clinical technique of fabricating an inlay using silver amalgam for restoring a large cervical abrasion cavity. A patient with large and deep cervical abrasion cavity in relation to mandibular right posterior region was reported. The impression of the abrasive cavity was done using rubber base impression material. Later, cast was fabricated, amalgam was condensed into the cavity, contoured and inlay was prepared. Fit of the inlay was checked on the patient, thereafter it was finished and polished and cemented using luting glass ionomer cement.
Complex and Difficult Clinical Patients: Reflections on Fernández-Álvarez's Integrative Psychotherapy Model as Applied to the Case of "Sonia"
Authors: Castaneiras Claudia , Fernandez-Alvarez Hector
Published: April 2014

Fernandez-A
Suppression of Alzheimer-Associated Inflammation by Microglial Prostaglandin-E2EP4 Receptor Signaling
Authors: Woodling Nathaniel S. , Wang Qian , Priyam Prachi G. , Larkin Paul , Shi Ju , Johansson Jenny U. , Zagol-Ikapitte Irene , Boutaud Olivier , Andreasson Katrin I.
Published: April 2014

A persistent and nonresolving inflammatory response to accumulating Aβ peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating Aβ peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many proinflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing Aβ-induced inflammation represent a relatively unexplored area. Here we report that signaling through the prostaglandin-E2(PGE2) EP4 receptor potently suppresses microglial inflammatory responses to Aβ42peptides. In cultured microglial cells, EP4 stimulation attenuated levels of Aβ42-induced inflammatory factors and potentiated phagocytosis of Aβ42. Microarray analysis demonstrated that EP4 stimulation broadly opposed Aβ42-driven gene expression changes in microglia, with enrichment for targets of IRF1, IRF7, and NF-κB transcription factors.In vivo, conditional deletion of microglial EP4 in APPSwe-PS1ΔE9(APP-PS1) mice conversely increased inflammatory gene expression, oxidative protein modification, and Aβ deposition in brain at early stages of pathology, but not at later stages, suggesting an early anti-inflammatory function of microglial EP4 signaling in the APP-PS1 model. Finally, EP4 receptor levels decreased significantly in human cortex with progression from normal to AD states, suggesting that early loss of this beneficial signaling system in preclinical AD development may contribute to subsequent progression of pathology.
Valence-Specific Effects ofBDNFVal66Met Polymorphism on Dopaminergic Stress and Reward Processing in Humans
Authors: Peciña Marta , Martínez-Jauand Mercedes , Love Tiffany , Heffernan Joseph , Montoya Pedro , Hodgkinson Colin , Stohler Christian S. , Goldman David , Zubieta Jon-Kar
Published: April 2014

Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (DA) cells within the ventral tegmental area (VTA)/nucleus accumbens (NAc) circuitry appear to be a candidate mechanism for the neuroadaptive changes that follow stress and reward responses in animal models. However, the role of theBDNFgene variants in responses to salient cues through DA neurotransmission in humans remains unexplored. Here, we studied the effect of the common functionalBDNFVal66Met (rs6265) polymorphism on rewarding experiences in the striatum and DA-mediated responses to stress. Seventy-two healthy controls were genotyped for theBDNFVal66Met polymorphism and underwent the monetary incentive delay task during an functional magnetic resonance imaging (fMRI) session. Forty-nine of them also underwent a sustained pain challenge with and without placebo administration with potential analgesic properties during PET measures of DA D2/3-receptor-mediated neurotransmission. Neuroimaging results revealed a significant effect ofBDNF(Met66carriers > Val/Val) on brain responses during the anticipation of monetary losses, baseline D2/3receptor availability, and pain-stress-induced DA release in the NAc. Conversely, BDNF Met66carriers showed no activation in response to monetary gains and a blunted DA response to the analgesic placebo in the NAc. These results provide initial human evidence regarding the effect of theBDNFVal66Met polymorphism on DA-mediated responses to stress, its cognitive regulation by positive expectations, and the anticipatory responses to monetary gains and losses in the VTA-NAc pathway. Our results are of relevance to the neurobiology of stress and reward interactions and the pathophysiology of stress-related disorders.
Developmental Changes in the Organization of Functional Connections between the Basal Ganglia and Cerebral Cortex
Authors: Greene Deanna J. , Laumann Timothy O. , Dubis Joseph W. , Ihnen S. Katie , Neta Maital , Power Jonathan D. , Pruett John R. , Black Kevin J. , Schlaggar Bradley L.
Published: April 2014

The basal ganglia (BG) comprise a set of subcortical nuclei with sensorimotor, cognitive, and limbic subdivisions, indicative of functional organization. BG dysfunction in several developmental disorders suggests the importance of the healthy maturation of these structures. However, few studies have investigated the development of BG functional organization. Using resting-state functional connectivity MRI (rs-fcMRI), we compared human child and adult functional connectivity of the BG with rs-fcMRI-defined cortical systems. Because children move more than adults, customized preprocessing, including volume censoring, was used to minimize motion-induced rs-fcMRI artifact. Our results demonstrated functional organization in the adult BG consistent with subdivisions previously identified in anatomical tracing studies. Group comparisons revealed a developmental shift in bilateral posterior putamen/pallidum clusters from preferential connectivity with the somatomotor “face” system in childhood to preferential connectivity with control/attention systems (frontoparietal, ventral attention) in adulthood. This shift was due to a decline in the functional connectivity of these clusters with the somatomotor face system over development, and no change with control/attention systems. Applying multivariate pattern analysis, we were able to reliably classify individuals as children or adults based on BG–cortical system functional connectivity. Interrogation of the features driving this classification revealed, in addition to the somatomotor face system, contributions by the orbitofrontal, auditory, and somatomotor hand systems. These results demonstrate that BG–cortical functional connectivity evolves over development, and may lend insight into developmental disorders that involve BG dysfunction, particularly those involving motor systems (e.g., Tourette syndrome).
Nerve Injury-Induced Neuropathic Pain Causes Disinhibition of the Anterior Cingulate Cortex
Authors: Blom Sigrid Marie , Pfister Jean-Pascal , Santello Mirko , Senn Walter , Nevian Thomas
Published: April 2014

Neuropathic pain caused by peripheral nerve injury is a debilitating neurological condition of high clinical relevance. On the cellular level, the elevated pain sensitivity is induced by plasticity of neuronal function along the pain pathway. Changes in cortical areas involved in pain processing contribute to the development of neuropathic pain. Yet, it remains elusive which plasticity mechanisms occur in cortical circuits. We investigated the properties of neural networks in the anterior cingulate cortex (ACC), a brain region mediating affective responses to noxious stimuli. We performed multiple whole-cell recordings from neurons in layer 5 (L5) of the ACC of adult mice after chronic constriction injury of the sciatic nerve of the left hindpaw and observed a striking loss of connections between excitatory and inhibitory neurons in both directions. In contrast, no significant changes in synaptic efficacy in the remaining connected pairs were found. These changes were reflected on the network level by a decrease in the mEPSC and mIPSC frequency. Additionally, nerve injury resulted in a potentiation of the intrinsic excitability of pyramidal neurons, whereas the cellular properties of interneurons were unchanged. Our set of experimental parameters allowed constructing a neuronal network model of L5 in the ACC, revealing that the modification of inhibitory connectivity had the most profound effect on increased network activity. Thus, our combined experimental and modeling approach suggests that cortical disinhibition is a fundamental pathological modification associated with peripheral nerve damage. These changes at the cortical network level might therefore contribute to the neuropathic pain condition.
Source-Reconstruction of Event-Related Fields Reveals Hyperfunction and Hypofunction of Cortical Circuits in Antipsychotic-Naive, First-Episode Schizophrenia Patients during Mooney Face Processing
Authors: Rivolta Davide , Castellanos Nazareth P. , Stawowsky Cerisa , Helbling Saskia , Wibral Michael , Grützner Christine , Koethe Dagmar , Birkner Katharina , Kranaster Laura , Enning Frank , Singer Wolf , Leweke F. Markus , Uhlhaas Peter J.
Published: April 2014

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n= 14) and healthy control participants (n= 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250 components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A′). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission.
The Brain's Temporal Dynamics from a Collective Decision to Individual Action
Authors: Charpentier Caroline J. , Moutsiana Christina , Garrett Neil , Sharot Tali
Published: April 2014

Social animals constantly make decisions together. What determines if individuals will subsequently adjust their behavior to align with collective choices? Here, using functional magnetic resonance imaging in humans, we characterize a novel temporal model of brain response from the time a collective decision is made to the time an individual action is required. We reveal that whether a behavioral modification will occur is determined not necessarily by the brain's response to the initial social influence, but by how that response (specifically in the orbitofrontal cortex; OFC) is mirrored at a later time when the individual selects their own action. This result suggests that the OFC may reconstitute an initial state of collective influence when individual action is subsequently needed. Importantly, these dynamics vary across individuals as a function of trait conformity and mediate the relationship between this personality characteristic and behavioral adjustment toward the group.
The Generation of Antiphase Oscillations and Synchrony by a Rebound-Based Vertebrate Central Pattern Generator
Authors: Li Wen-Chang , Merrison-Hort Robert , Zhang Hong-Yan , Borisyuk Roman
Published: April 2014

Many neural circuits are capable of generating multiple stereotyped outputs after different sensory inputs or neuromodulation. We have previously identified the central pattern generator (CPG) forXenopustadpole swimming that involves antiphase oscillations of activity between the left and right sides. Here we analyze the cellular basis for spontaneous left–right motor synchrony characterized by simultaneous bursting on both sides at twice the swimming frequency. Spontaneous synchrony bouts are rare in most tadpoles, and they instantly emerge from and switch back to swimming, most frequently within the first second after skin stimulation. Analyses show that only neurons that are active during swimming fire action potentials in synchrony, suggesting both output patterns derive from the same neural circuit. The firing of excitatory descending interneurons (dINs) leads that of other types of neurons in synchrony as it does in swimming. During synchrony, the time window between phasic excitation and inhibition is 7.9 ± 1 ms, shorter than that in swimming (41 ± 2.3 ms). The occasional, extra midcycle firing of dINs during swimming may initiate synchrony, and mismatches of timing in the left and right activity can switch synchrony back to swimming. Computer modeling supports these findings by showing that the same neural network, in which reciprocal inhibition mediates rebound firing, can generate both swimming and synchrony without circuit reconfiguration. Modeling also shows that lengthening the time window between phasic excitation and inhibition by increasing dIN synaptic/conduction delay can improve the stability of synchrony.
Activity-Dependent Tau Protein Translocation to Excitatory Synapse Is Disrupted by Exposure to Amyloid-Beta Oligomers
Authors: Frandemiche Marie Lise , De Seranno Sandrine , Rush Travis , Borel Eve , Elie Auréliane , Arnal Isabelle , Lanté Fabien , Buisson Alain
Published: April 2014

Tau is a microtubule-associated protein well known for its stabilization of microtubules in axons. Recently, it has emerged that tau participates in synaptic function as part of the molecular pathway leading to amyloid-beta (Aβ)-driven synaptotoxicity in the context of Alzheimer's disease. Here, we report the implication of tau in the profound functional synaptic modification associated with synaptic plasticity. By exposing murine cultured cortical neurons to a pharmacological synaptic activation, we induced translocation of endogenous tau from the dendritic to the postsynaptic compartment. We observed similar tau translocation to the postsynaptic fraction in acute hippocampal slices subjected to long-term potentiation. When we performed live confocal microscopy on cortical neurons transfected with human-tau-GFP, we visualized an activity-dependent accumulation of tau in the postsynaptic density. Coprecipitation using phalloidin revealed that tau interacts with the most predominant cytoskeletal component present, filamentous actin. Finally, when we exposed cortical cultures to 100 nmhuman synthetic Aβ oligomers (Aβo's) for 15 min, we induced mislocalization of tau into the spines under resting conditions and abrogated subsequent activity-dependent synaptic tau translocation. These changes in synaptic tau dynamics may rely on a difference between physiological and pathological phosphorylation of tau. Together, these results suggest that intense synaptic activity drives tau to the postsynaptic density of excitatory synapses and that Aβo-driven tau translocation to the spine deserves further investigation as a key event toward synaptotoxicity in neurodegenerative diseases.
Overexpression of the Steroidogenic Enzyme Cytochrome P450 Side Chain Cleavage in the Ventral Tegmental Area Increases 3α,5α-THP and Reduces Long-Term Operant Ethanol Self-Administration
Authors: Cook Jason B. , Werner David F. , Maldonado-Devincci Antoniette M. , Leonard Maggie N. , Fisher Kristen R. , O'Buckley Todd K. , Porcu Patrizia , McCown Thomas J. , Besheer Joyce , Hodge Clyde W. , Morrow A. Leslie
Published: April 2014

Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.
Optogenetic-Mediated Release of Histamine Reveals Distal and Autoregulatory Mechanisms for Controlling Arousal
Authors: Williams Rhîannan H. , Chee Melissa J.S. , Kroeger Daniel , Ferrari Loris L. , Maratos-Flier Eleftheria , Scammell Thomas E. , Arrigoni Elda
Published: April 2014

Histaminergic neurons in the tuberomammillary nucleus (TMN) are an important component of the ascending arousal system and may form part of a “flip–flop switch” hypothesized to regulate sleep and wakefulness. Anatomical studies have shown that the wake-active TMN and sleep-active ventrolateral preoptic nucleus (VLPO) are reciprocally connected, suggesting that each region can inhibit its counterpart when active. In this study, we determined how histamine affects the two branches of this circuit. We selectively expressed channelrhodopsin-2 (ChR2) in TMN neurons and used patch-clamp recordings in mouse brain slices to examine the effects of photo-evoked histamine release in the ventrolateral TMN and VLPO. Photostimulation decreased inhibitory GABAergic inputs to the ventrolateral TMN neurons but produced a membrane hyperpolarization and increased inhibitory synaptic input to the VLPO neurons. We found that in VLPO the response to histamine was indirect, most likely via a GABAergic interneuron. Our experiments demonstrate that release of histamine from TMN neurons can disinhibit the TMN and suppresses the activity of sleep-active VLPO neurons to promote TMN neuronal firing. This further supports the sleep–wake “flip–flop switch” hypothesis and a role for histamine in stabilizing the switch to favor wake states.
Infralimbic BDNF/TrkB Enhancement of GluN2B Currents Facilitates Extinction of a Cocaine-Conditioned Place Preference
Authors: Otis James M. , Fitzgerald Michael K. , Mueller Devin
Published: April 2014

Brain-derived neurotrophic factor (BDNF) regulates synaptic activity and behavioral flexibility, and reduction of BDNF strongly predicts psychiatric disorders and cognitive dysfunction. Restoration of BDNF-dependent activity could alleviate these impairments, but BDNF has limited clinical utility due to its pharmacokinetics. Here we demonstrate that activation of a primary BDNF target, the tropomyosin-related kinase B (TrkB) receptor, enhances the amplitude and prolongs the decay kinetics ofN-methyl-d-aspartate receptor (NMDAR) currents in male rat infralimbic prefrontal pyramidal neurons. Moreover, these effects were prevented and reversed by blockade of NMDARs containing the GluN2B subunit. Our results show that this signaling cascade bidirectionally regulates extinction of a cocaine-induced conditioned place preference (CPP), a task that requires behavioral flexibility. Blockade of infralimbic TrkB receptors or GluN2B-containing NMDARs disrupted consolidation of extinction of the CPP. In contrast, extinction was strengthened by potentiation of TrkB receptor activity with infralimbic infusions of BDNF or systemic injections of 7,8 dihydroxyflavone (7,8DHF), the newly synthesized TrkB receptor agonist. The 7,8DHF-induced enhancement of extinction was prevented by infralimbic infusions of a GluN2B-specific receptor antagonist, demonstrating that TrkB receptor activation enhances extinction of cocaine-CPP via GluN2B-containing NMDARs. Together, infralimbic TrkB receptor activation strengthens GluN2B-containing NMDAR currents to support extinction learning. TrkB receptor agonists would therefore be useful as pharmacological adjuncts for extinction-based therapies for treatment of psychiatric disorders associated with reduced BDNF activity.
Conceptualizing Critical Qualitative Research In/Against Global Neoliberalisms
Authors: Cannella Gaile S. , Wolff Kenya
Published: April 2014

In the fall of 2010, a group of early childhood scholars concerned with the impact of neoliberalism on those who are younger met to discuss the situation and the various performances of neoliberalism in diverse local spaces. The global condition (as entangled neoliberal assemblages) requires new critical qualitative research perspectives and conceptualizations, unthought methods, and ways to center traditionally marginalized theories and understandings. This article introduces, and overviews, the qualitative research used by the various scholars in different locations around the globe from within a theoretical perspective that predominantly employs the Deleuze/Guattari notion of assemblage as applicable to qualitative research.
Kei tua i te awe māpara
Authors: Ritchie Jenny , Skerrett Mere , Rau Cheryl
Published: April 2014

In this paper, we traverse both historical and contemporary discourses pertaining to early childhood care and education in Aotearoa New Zealand, offering a genealogical discursive analysis of assumptions of white superiority. It is proposed that such an analysis delivers a platform from which to launch a project of unmasking the recent and ongoing impact of neoliberal policies in our country. Two key documents are highlighted: the founding document of our nation, Te Tiriti o Waitangi/The Treaty of Waitangi, and the New Zealand early childhood curriculum, Te Whāriki. These documents are unusual both within our country, and internationally, in that they offer a framework for bi-epistemological approaches to both education and social organisation more widely. Revisiting these documents in the context of uncovering the subtle racism that underpins assumptions of white superiority provides a platform for countercolonial, ethical reenvisioning of our educational becomings.
Researching Neoliberal and Neocolonial Assemblages in Early Childhood Education
Authors: Pacini-Ketchabaw Veronica , Nxumalo Fikile , Rowan Mary Caroline
Published: April 2014

The article provides a discussion of “researching” neoliberalisms and neocolonialisms in white settler colonial societies such as Canada. It addresses the research implications after conceptualizing neoliberalisms as assemblages that are always already implicated in colonial histories. Specifically, the article discusses the need to rethink methodologies when neoliberalisms do not follow coherent directions, the kinds of methodological and research approaches necessary for the fluid and nonlinear movements of neoliberalisms and neocolonialisms, and how neoliberalisms and neocolonialisms as connected assemblages open up early childhood research practices that attend to colonial pastpresents.