bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesizing Sound from Turbulent Field using Sound Textures for Interactive Fluid Simulation
Authors: Dobashi Yoshinori , Yamamoto Tsuyoshi , Nishita Tomoyuki
Published: August 2004

Sound is an indispensable element for the simulation of a realistic virtual environment. Therefore, there has been much recent research focused on the simulation of realistic sound effects. This paper proposes a method for creating sound for turbulent phenomena such as fire. In a turbulent field, the complex motion of vortices leads to the generation of sound. This type of sound is called a vortex sound. The proposed method simulates a vortex sound by computing vorticity distributions using computational fluid dynamics. Sound textures for the vortex sound are first created in a pre‐process step. The sound is then created at interactive rates by using these sound textures. The usefulness of the proposed method is demonstrated by applying it to the simulation of the sound of fire and other turbulent phenomena.

Categories and Subject Descriptors (according to ACM CCS): I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism ‐ Animation; I.6.8 [Simulation and Modeling]: Types of Simulation ‐ Animation; I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism; I.6.3 [Simulation and Modeling]: Applications; H.5.5 [Information Interfaces and Presentation]: Sound and Music Computing ‐ Methodologies and techniques, Modeling.
DiFi: Fast 3D Distance Field Computation Using Graphics Hardware
Authors: Sud Avneesh , Otaduy Miguel A. , Manocha Dinesh
Published: August 2004

We present an algorithm for fast computation of discretized 3D distance fields using graphics hardware. Given a set of primitives and a distance metric, our algorithm computes the distance field for each slice of a uniform spatial grid baly rasterizing the distance functions of the primitives. We compute bounds on the spatial extent of the Voronoi region of each primitive. These bounds are used to cull and clamp the distance functions rendered for each slice. Our algorithm is applicable to all geometric models and does not make any assumptions about connectivity or a manifold representation. We have used our algorithm to compute distance fields of large models composed of tens of thousands of primitives on high resolution grids. Moreover, we demonstrate its application to medial axis evaluation and proximity computations. As compared to earlier approaches, we are able to achieve an order of magnitude improvement in the running time.

Categories and Subject Descriptors (according to ACM CCS): I.3.3 [Computer Graphics]: Distance fields, Voronoi regions, graphics hardware, proximity computations
Point Cloud Collision Detection
Authors: Klein Jan , Zachmann Gabriel
Published: August 2004

In the past few years, many efficient rendering and surface reconstruction algorithms for point clouds have been developed. However, collision detection of point clouds has not been considered until now, although this is a prerequisite to use them for interactive or animated 3D graphics.

We present a novel approach for time‐critical collision detection of point clouds. Based solely on the point representation, it can detect intersections of the underlying implicit surfaces. The surfaces do not need to be closed.

We construct a point hierarchy where each node stores a sufficient sample of the points plus a sphere covering of a part of the surface. These are used to derive criteria that guide our hierarchy traversal so as to increase convergence. One of them can be used to prune pairs of nodes, the other one is used to prioritize still to be visited pairs of nodes. At the leaves we efficiently determine an intersection by estimating the smallest distance.

We have tested our implementation for several large point cloud models. The results show that a very fast and precise answer to collision detection queries can always be given.

Categories and Subject Descriptors (according to ACM CCS): G.1.2 [Numerical Analysis]: Approximation of surfaces and contours I.3.5 [Computer Graphics]: Computational Geometry and Object‐Modeling[Geometric algorithms, languages and systems; object hierarchy; physically‐based modeling] I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism[Animation; virtual reality]
A Progressive Rendering Algorithm Using an Adaptive Perceptually Based Image Metric
Authors: Farrugia Jean‐Philippe , Péroche Bernard
Published: August 2004

In this paper, we propose to solve the global illumination problem through a progressive rendering method relying on an adaptive sampling of the image space. The refinement of this sample scheme is driven by an image metric based on a powerful vision model. A Delaunay triangulation of the sampled points is followed by a classification of these triangles into three classes. By interpolating each triangle according to the class it belongs to, we can obtain a high quality image by computing only a fraction of all the pixels and thus saving computation time.

Categories and Subject Descriptors (according to ACM CCS): I.3.3 [Computer Graphics]: Perceptual Rendering, Global illumination
Coherent Hierarchical Culling: Hardware Occlusion Queries Made Useful
Authors: Bittner Jiří , Wimmer Michael , Piringer Harald , Purgathofer Werner
Published: August 2004

We present a simple but powerful algorithm for optimizing the usage of hardware occlusion queries in arbitrary complex scenes. Our method minimizes the number of issued queries and reduces the delays due to the latency of query results. We reuse the results of occlusion queries from the last frame in order to initiate and schedule the queries in the next frame. This is done by processing nodes of a spatial hierarchy in a front‐to‐back order and interleaving occlusion queries with rendering of certain previously visible nodes. The proposed scheduling of the queries makes use of spatial and temporal coherence of visibility. Despite its simplicity, the algorithm achieves good culling efficiency for scenes of various types. The implementation of the algorithm is straightforward and it can be easily integrated in existing real‐time rendering packages based on common hierarchical data structures.

Categories and Subject Descriptors (according to ACM CCS): I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism
Hardware‐Accelerated Rendering of Photo Hulls
Authors: Li Ming , Magnor Marcus , Seidel Hans‐Peter
Published: August 2004

This paper presents an efficient hardware‐accelerated method for novel view synthesis from a set of images or videos. Our method is based on the photo hull representation, which is the maximal photo‐consistent shape. We avoid the explicit reconstruction of photo hulls by adopting a view‐dependent plane‐sweeping strategy. From the target viewpoint slicing planes are rendered with reference views projected onto them. Graphics hardware is exploited to verify the photo‐consistency of each rasterized fragment. Visibilities with respect to reference views are properly modeled, and only photo‐consistent fragments are kept and colored in the target view. We present experiments with real images and animation sequences. Thanks to the more accurate shape of the photo hull representation, our method generates more realistic rendering results than methods based on visual hulls. Currently, we achieve rendering frame rates of 2–3 fps. Compared to a pure software implementation, the performance of our hardware‐accelerated method is approximately 7 times faster.

Categories and Subject Descriptors (according to ACM CCS): CR Categories: I.3.3 [Computer Graphics]: Picture/Image Generation; I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism.
Optimized Sub‐Sampling of Point Sets for Surface Splatting
Authors: Wu Jainhua , Kobbelt Leif
Published: August 2004

Using surface splats as a rendering primitive has gained increasing attention recently due to its potential for high‐performance and high‐quality rendering of complex geometric models. However, as with any other rendering primitive, the processing costs are still proportional to the number of primitives that we use to represent a given object. This is why complexity reduction for point‐sampled geometry is as important as it is, e.g., for triangle meshes. In this paper we present a new sub‐sampling technique for dense point clouds which is specifically adjusted to the particular geometric properties of circular or elliptical surface splats. A global optimization scheme computes an approximately minimal set of splats that covers the entire surface while staying below a globally prescribed maximum error toleranceε. Since our algorithm converts pure point sample data into surface splats with normal vectors and spatial extent, it can also be considered as a surface reconstruction technique which generates a hole‐free piecewise linearC−1continuous approximation of the input data. Here we can exploit the higher flexibility of surface splats compared to triangle meshes. Compared to previous work in this area we are able to obtain significantly lower splat numbers for a given error tolerance.
Deferred Splatting
Authors: Guennebaud Gaël , Barthe Loïc , Paulin Mathias
Published: August 2004

In recent years it has been shown that, above a certain complexity, points become the most efficient rendering primitives. Although the programmability of the lastest graphics hardware allows efficient implementation of high quality surface splatting algorithms, their performance remains below those obtained with simpler point based rendering algorithms when they are used for scenes of high complexity. In this paper, our goal is to apply high quality point based rendering algorithms on complex scenes. For this purpose, we show how to take advantage of temporal coherency in a very accurate hardware accelerated point selection algorithm allowing the expensive computations to be peformed only on visible points. Our algorithm is based on a multi‐pass hardware accelerated EWA splatting. It is also suitable for any rendering application since no pre‐process is needed and no assumption is made on the data structure. In addition, we briefly discuss the association of our method with other existing culling techniques and optimization for particular applications.

Categories and Subject Descriptors (according to ACM CCS): I.3.3 [Computer Graphics]: Viewing algorithms
Exchanging Faces in Images
Authors: Blanz Volker , Scherbaum Kristina , Vetter Thomas , Seidel Hans‐Peter
Published: August 2004

Pasting somebody's face into an existing image with traditional photo retouching and digital image processing tools has only been possible if both images show the face from the same viewpoint and with the same illumination. However, this is rarely the case for given pairs of images. We present a system that exchanges faces across large differences in viewpoint and illumination. It is based on an algorithm that estimates 3D shape and texture along with all relevant scene parameters, such as pose and lighting, from single images. Manual interaction is reduced to clicking on a set of about 7 feature points, and marking the hairline in the target image. The system can be used for image processing, virtual try‐on of hairstyles, and face recognition. By separating face identity from imaging conditions, our approach provides an abstract representation of images and a novel, high‐level tool for image manipulation.

Categories and Subject Descriptors (according to ACM CCS): I.3.7 [Computer Graphics]: Animation
High Resolution Acquisition, Learning and Transfer of Dynamic 3‐D Facial Expressions
Authors: Wang Yang , Huang Xiaolei , Lee Chan‐Su , Zhang Song , Li Zhiguo , Samaras Dimitris , Metaxas Dimitris , Elgammal Ahmed , Huang Peisen
Published: August 2004

Synthesis and re‐targeting of facial expressions is central to facial animation and often involves significant manual work in order to achieve realistic expressions, due to the difficulty of capturing high quality dynamic expression data. In this paper we address fundamental issues regarding the use of high quality dense 3‐D data samples undergoing motions at video speeds, e.g. human facial expressions. In order to utilize such data for motion analysis and re‐targeting, correspondences must be established between data in different frames of the same faces as well as between different faces. We present a data driven approach that consists of four parts: 1) High speed, high accuracy capture of moving faces without the use of markers, 2) Very precise tracking of facial motion using a multi‐resolution deformable mesh, 3) A unified low dimensional mapping of dynamic facial motion that can separate expression style, and 4) Synthesis of novel expressions as a combination of expression styles. The accuracy and resolution of our method allows us to capture and track subtle expression details. The low dimensional representation of motion data in a unified embedding for all the subjects in the database allows for learning the most discriminating characteristics of each individual's expressions as that person's “expression style”. Thus new expressions can be synthesized, either as dynamic morphing between individuals, or as expression transfer from a source face to a target face, as demonstrated in a series of experiments.

Categories and Subject Descriptors (according to ACM CCS): I.3.7 [Computer Graphics]: Animation; I.3.5 [Computer Graphics]: Curve, surface, solid, and object representations; I.3.3 [Computer Graphics]: Digitizing and scanning; I.2.10 [Artificial intelligence]: Motion ; I.2.10 [Artificial intelligence]: Representations, data structures, and transforms; I.2.10 [Artificial intelligence]: Shape; I.2.6 [Artificial intelligence]: Concept learning
Hierarchical Retargetting of Fine Facial Motions
Authors: Na Kyunggun , Jung Moonryul
Published: August 2004

We present a novel technique for retargetting captured facial animation to new facial models. We use dense motion data that can express fine motions such as wrinkles. We use a normal mesh, which is a special multi‐resolution mesh, to represent source and target models. A normal mesh is defined by the base mesh and sequence of normal offsets from it. Our retargetting consists of two steps: base mesh and detail mesh retargetting. For base mesh retargetting, we use an example‐based technique to take advantage of the intuition of the user in specifying the similarity between source and target expressions. In detail mesh retargetting, the variations of normal offsets in the source mesh are hierarchically computed and transferred to the target mesh. Our retargetting scheme is able to produce robust and delicate results for unusual target models from highly detailed motion data.

Categories and Subject Descriptors (according to ACM CCS): I.3.7 [Computer Graphics]: Three Dimensional Graphics and Realism ‐ Animation; I.3.5 [Computer Graphics]: Computational Geometry and Object Modelling ‐ hierarchy and geometric transformation, object hierarchy
Sustainability Policy and Environmental Policy
Authors: Pezzey John C. V.
Published: August 2004

A theoretical, representative‐agent economy with a depletable resource stock, polluting emissions and productive capital is used to contrast environmental policy, which internalises externalised environmental values, with sustainability policy, which achieves some form of intergenerational equity. The obvious environmental policy comprises an emissions tax and a resource stock subsidy, each equal to the respective external cost or benefit. Sustainability policy comprises an incentive affecting the choice between consumption and investment, and can be a consumption tax, capital subsidy or investment subsidy, or a combination thereof. Environmental policy can reduce the strength of the sustainability policy needed. More specialised results are derived in a small open economy with no environmental effects on utility.
Taxation of Mobile Factors as Insurance under Uncertainty
Authors: Lee Kangoh
Published: August 2004

This paper considers the effects of the taxation of mobile factors, i.e., capital, under uncertainty. The wages earned by residents of a jurisdiction are uncertain due to random shocks. Since the uncertain wages in a jurisdiction depend on the amount of mobile capital employed in the jurisdiction, and since taxation alters the quantity of capital employed, taxation affects the riskiness of uncertain wages. In particular, the taxation of capital moderates the fluctuation of uncertain wages, thereby providing insurance. For this reason, jurisdictions use distortionary capital taxation even if lump‐sum taxation is available. In addition, this insurance effect counteracts the tendency toward too low tax rates on capital arising from tax competition, and possibly improves the efficiency of tax competition.
Using Q‐Methodology to Involve People with Intellectual Disability in Evaluating Person‐Centred Planning
Authors: Combes Helen , Hardy Gillian , Buchan Linda
Published: August 2004

Objectives  Person‐centred approaches do not easily lend themselves to standard methods of evaluation. This study develops a technique that will involve service users and their circle of support in making individual plans.

Methodology  Q‐methodology is a phenomenological approach, which enables the researcher to co‐construct the stories of many people. Two people with learning disabilities and seven members of their circle of support were identified to participate in the study. They attended a stakeholder meeting to identify 36 valued activities. The 16 participants then completed a Q‐sort using photographs to represent these activities. These sorts were then interpreted using Q‐methodology.

Results  There were a number of intercorrelations between the card sorts. Principle component analysis showed that two factors accounted for 73% of the variance of the data. The two clusters represented the members of each person's circle of support. Analysis and comparison of the factors have highlighted the similarities and differences between individuals and their circle of support.

Conclusions  This study shows that Q‐methodology is a useful adjunct to person‐centred planning. Looking at and interpreting the data, which emerge through Q‐methodology, hashighlighted both similarities and individual differences for goal planning. It has also highlighted potential areas for service change and development. Using Q‐sorts over time may be a way to demonstrate the subjective change in peoples' values that occur through person‐centred planning (PCP).
Religious Expression amongst Adults with Intellectual Disabilities
Authors: Turner Susannah , Hatton Chris , Shah Robina , Stansfield Julie , Rahim Nabela
Published: August 2004

Background  Although religion is an important part of many people's lives, little is known about the role of religion in the lives of people with intellectual disabilities.

Method  Semi‐structured face‐to‐face interviews were conducted with 29 people with intellectual disabilities of a range of faiths (various Christian denominations, Islam and Hindu dharma). Participants were asked about the meaning of religion for them, the role of religion in their lives and the attitudes of others towards religious expression. All interviews were audio‐recorded, transcribed and thematically analysed.

Results  Participants expressed strong religious identities. Prayer was a particularly popular form of religious expression, with other forms of religious expression often hindered by services or faith agencies. Some individuals expressed how their religious faith was not recognized by services or faith agencies.

Conclusions  Services and faith agencies need to recognize the importance of religion in the lives of many people with intellectual disabilities, and support religious expression in this group.
Service Provision for Young People with Intellectual Disabilities and Additional Mental Health Needs: Service‐providers’ Perspectives
Authors: Scior Katrina , Grierson Kate
Published: August 2004

Background  Very little is known about young people with intellectual disabilities who experience additional mental health problems. The perspective of service providers has been highlighted as one unresearched area.

Method  Semi‐structured interviews were completed with senior service providers. Aims: (1) to explore experiences of working with young people with intellectual disabilities and additional mental health problems and their families; (2) to examine views on services’ ability to meet the needs of this group.

Results  Service providers identified a gulf between current policy and the reality for this group, not least in terms of all agencies working in partnership. All agencies described instances when young people in this group fall through gaps between services. Interviewees identified a range of factors that promote good outcomes.

Conclusions  The results suggest that the focus of current policies to promote joint working needs to be broadened beyond health and social services to ensure much improved links with education providers and the voluntary sector if the needs of this group are to be met.
Negative Emotional Reactions to Challenging Behaviour and Staff Burnout: Two Replication Studies
Authors: Rose David , Horne Sharon , Rose John L. , Hastings Richard P.
Published: August 2004

Background  Hastings, R. P. [American Journal on Mental Retardation (2002) Vol. 107, pp. 455–467] hypothesized that staff negative emotional reactions to challenging behaviour might accumulate over time to affect staff well‐being. Only one previous study (Mitchell, G.& Hastings, R. P. [American Journal on Mental Retardation (2001) Vol. 106, pp. 448–459] has explored this relationship. The present analyses were designed to replicate these findings.

Methods  Data were analysed from two samples of staff. In study 1, 101 staff rated their typical emotional reactions to challenging behaviours experienced as a part of their work and completed the Maslach Burnout Inventory (MBI). In study 2, 99 staff rated their negative emotional reactions to written challenging behaviour vignettes and also completed the MBI.

Results  In both studies, significant positive correlations were found between negative emotional reactions to challenging behaviour and emotional exhaustion and depersonalization burnout but no association was found with personal accomplishment scores.

Conclusions  These findings replicate previous results, but cannot be used to support the putative causal relationship between emotional reactions to challenging behaviour and staff well‐being. Clinical implications of a focus on staff emotional reactions to challenging behaviour are discussed.
Social and Professional Support for Parents of Adolescents with Severe Intellectual Disabilities
Authors: White Nia , Hastings Richard P.
Published: August 2004

Background  Previous research has identified various dimensions of social support that are positively associated with parental well‐being. However, most research does not include multiple measures of social support and uses heterogeneous samples in terms of child characteristics such as age and severity of intellectual disability.

Methods  Thirty‐three parents of adolescent children with moderate–profound intellectual disabilities completed measures of parental well‐being (stress, anxiety and depression, and caregiving satisfaction), social support (informal and formal sources, and practical and emotional support), and child characteristics (adaptive and problem behaviours).

Results  Correlation analyses showed that parental well‐being was associated with the child's adaptive and problem behaviours and with the child's autism diagnosis. Parents’ ratings of the helpfulness of informal sources of support (spouse, extended family, friends, etc.) was most reliably associated with parental well‐being, and remained so after controlling for child characteristics. Parents’ access of service and professional support was not associated with parental well‐being, but there was some evidence that it was related to their child's needs.

Conclusions  The research emphasizes the significance of including multiple measures of social support in research with families of children with an intellectual disability. Furthermore, the possibility that parents, during their child's adolescence, may be especially vulnerable to the disruption of their informal support networks is an important practical consideration.
Friendship Activities of Adults with Intellectual Disabilities in Supported Accommodation in Northern England
Authors: Emerson Eric , McVilly Keith
Published: August 2004

Background  Despite there being considerable evidence to suggest that friendships are central to health and well‐being, relatively little attention had been paid to the friendships of people with intellectual disabilities.

Methods  Friendship activities involving people with and without intellectual disabilities were measured over the preceding month in a sample of 1542 adults with intellectual disabilities receiving supported accommodation in nine geographical localities in Northern England.

Results  The results of the study indicate: (1) low levels of friendship activities among people with intellectual disabilities in supported accommodation; (2) people with intellectual disabilities are more likely to be involved in activities with friends who also have intellectual disabilities than with friends who do not have intellectual disabilities; (3) most friendship activities take place in the public domain rather than in more private settings (e.g. at home); (4) the setting in which a person lives is a more significant determinant of the form and content of activities with their friends than the characteristics of participants.

Conclusions  Further attention needs to be given to research and practice initiatives aimed at increasing the levels of friendship activities of people with intellectual disabilities.
Social Competence in Persons with Prader‐Willi, Williams and Down's Syndromes
Authors: Rosner Beth A. , Hodapp Robert M. , Fidler Deborah J. , Sagun Jaclyn N. , Dykens Elisabeth M.
Published: August 2004

Background  This study explores everyday social competence in the lives of persons with three genetic intellectual disability syndromes.

Methods  Using parent reports on the Social and Activity Competence domains of Achenbach's Child Behavior Checklist (CBCL), socially competent behaviours were examined in 58 persons with Williams syndrome, 54 persons with Prader‐Willi syndrome, and 65 persons with Down's syndrome.

Results  The Down's syndrome group showed the highest overall social competence scores, while individuals with Prader‐Willi syndrome fared worst in terms of their behaviour with others. The Williams syndrome group scored lowest in terms of skill with jobs and chores, and the Down's syndrome group showed the least skill in non‐sport activities. Regarding specific activities, musical activities were popular in both Williams syndrome and Down's syndrome, but more participants with Williams syndrome played musical instruments. Compared with the other groups, individuals with Prader‐Willi syndrome were five to 25 times more likely to play with jigsaw puzzles, and those with Williams syndrome were least likely to engage in any visual–spatial leisure activities. Age was found to be a positive correlate of social competence for the Williams and Down's syndrome groups, but not for the Prader‐Willi group.

Conclusions  Implications are discussed for interventions and for future behavioural phenotype work.
PARP‐1 gene disruption in mice preferentially protects males from perinatal brain injury
Authors: Hagberg Henrik , Wilson Mary Ann , Matsushita Hiroko , Zhu Changlian , Lange Mary , Gustavsson Malin , Poitras Marc F. , Dawson Ted M. , Dawson Valina L. , Northington Frances , Johnston Michael V.
Published: August 2004

Poly(ADP‐ribose) polymerase‐1 is over‐activated in the adult brain in response to ischemia and contributes to neuronal death, but its role in perinatal brain injury remains uncertain. To address this issue, 7‐day‐old wild‐type (wt) and PARP‐1 gene deficient (parp+/– and parp–/–) Sv129/CD‐1 hybrid mice were subjected to unilateral hypoxia‐ischemia and histologic damage was assessed 10 days later by two evaluators. Poly(ADP‐ribose) polymerase‐1 knockout produced moderate but significant (p < 0.05) protection in the total group of animals, but analysis by sex revealed that males were strongly protected (p < 0.05) in contrast to females in which there was no significant effect. Separate experiments demonstrated that PARP‐1 was activated over 1–24 h in both females and males after the insult in neonatal wt mice and rats using immnocytochemistry and western blotting for poly(ADP‐ribose). Brain levels of NAD+ were also significantly reduced, but the decrease of NAD+ during the early post‐hypoxia‐ischemia (HI) phase was only seen in males. The results indicate that hypoxia‐ischemia activates Poly(ADP‐ribose) polymerase‐1 in the neonatal brain and that the sex of the animal strongly influences its role in the pathogenesis of brain injury.
Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal‐regulated kinase activation
Authors: Sagara Yutaka , Vanhnasy Julie , Maher Pamela
Published: August 2004

Many of the physiological benefits attributed to flavonoids are thought to stem from their potent antioxidant and free radical scavenging properties. Recently, it was shown that flavonoids protect nerve cells from oxidative stress by multiple mechanisms, only one of which is directly related to their antioxidant activity, suggesting that specific flavonoids may have other properties that could make them useful in the treatment of conditions that lead to nerve cell death. In particular, it was asked if any flavonoid could mimic neurotrophic proteins. To examine this possibility, we looked at the ability of flavonoids to induce nerve cell differentiation using PC12 cells. PC12 cells were treated with a variety of flavonoids to determine if there was a correlation between their neuroprotective activity and their neurite outgrowth‐promoting activity. In addition, the signaling pathways required for flavonoid‐induced differentiation were examined. We found that only a small subset of the flavonoids that were neuroprotective could induce neurite outgrowth by an extracellular signal‐regulated kinase‐dependent process. There was a strong correlation between the concentrations of the flavonoids that were neuroprotective and the concentrations that induced differentiation. These results suggest that the consumption of specific flavonoids could have further beneficial effects on nerve cells following injury, in pathological conditions or in normal aging.
NFATc1 activates the acetylcholinesterase promoter in rat muscle
Authors: Cohen Tatiana V. , Randall William R.
Published: August 2004

Nuclear factor of activated T‐cells (NFAT) plays a role in the response of muscle to chronic contractile activity that can result in fiber type switching and hypertrophy. These effects are due in part to activation of target genes following Ca2+‐mediated nuclear translocation of NFAT. Acetylcholinesterase (AChE), a component of the neuromuscular junction, is regulated by chronic muscle and nerve activity through changes in intracellular Ca2+, suggesting that the Ache gene may be a potential downstream target of NFAT signaling. To determine whether elements of the Ache promoter are modulated by NFAT, we transiently co‐expressed reporter constructs driven by fragments of the Ache promoter with an NFATc1 that is constitutively translocated to the nucleus [NFATc1(S → A)] in rat muscle cultures. NFATc1 potentiated reporter activity when co‐transfected with constructs containing Ache genomic elements from −1280 to −490 bp upstream of transcription initiation. Electrophoretic mobility shift assays demonstrated strong binding to a potential NFAT element at −793 bp and weaker binding to one at −678 bp. Co‐transfection of promoter fragments, containing the binding sites at −793 and at −678 bp, with NFATc1(S → A) potentiated reporter activity, supporting sites of interaction with NFAT. Our data suggests a role for NFAT as a modulator of Ache gene transcription.
Mitochondrial permeability transition in neuronal damage promoted by Ca2+ and respiratory chain complex II inhibition
Authors: Maciel Evelise N. , Kowaltowski Alicia J. , Schwalm Fábio D. , Rodrigues Juliana M. , Souza Diogo O. , Vercesi Anibal E. , Wajner Moacir , Castilho Roger F.
Published: August 2004

Changes in mitochondrial integrity, reactive oxygen species release and Ca2+ handling are proposed to be involved in the pathogenesis of many neurological disorders including methylmalonic acidaemia and Huntington's disease, which exhibit partial mitochondrial respiratory inhibition. In this report, we studied the mechanisms by which the respiratory chain complex II inhibitors malonate, methylmalonate and 3‐nitropropionate affect rat brain mitochondrial function and neuronal survival. All three compounds, at concentrations which inhibit respiration by 50%, induced mitochondrial inner membrane permeabilization when in the presence of micromolar Ca2+ concentrations. ADP, cyclosporin A and catalase prevented or delayed this effect, indicating it is mediated by reactive oxygen species and mitochondrial permeability transition (PT). PT induced by malonate was also present in mitochondria isolated from liver and kidney, but required more significant respiratory inhibition. In brain, PT promoted by complex II inhibition was stimulated by increasing Ca2+ cycling and absent when mitochondria were pre‐loaded with Ca2+ or when Ca2+ uptake was prevented. In addition to isolated mitochondria, we determined the effect of methylmalonate on cultured PC12 cells and freshly prepared rat brain slices. Methylmalonate promoted cell death in striatal slices and PC12 cells, in a manner attenuated by cyclosporin A and bongkrekate, and unrelated to impairment of energy metabolism. We propose that under conditions in which mitochondrial complex II is partially inhibited in the CNS, neuronal cell death involves the induction of PT.
Iron‐sulfur enzyme mediated mitochondrial superoxide toxicity in experimental Parkinson's disease
Authors: Liang Li‐Ping , Patel Manisha
Published: August 2004

Mitochondrial oxidative stress is thought to be an important pathological mediator of neuronal death in Parkinson's disease. However, the precise mechanism by which mitochondrial oxidative stress mediates the death of dopaminergic neurons of the substantia nigra remains unclear. We tested the idea that neuronal damage in the MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) model of Parkinson's disease results, in part, from superoxide radical toxicity via inactivation of an iron‐sulfur (Fe‐S) protein, mitochondrial aconitase. Administration of MPTP in mice resulted in inactivation of mitochondrial aconitase, but not fumarase in the substantia nigra. MPTP treatment mobilized an early mitochondrial pool of iron detectable by bleomycin chelation that coincided with mitochondrial aconitase inactivation. MPTP‐induced mitochondrial aconitase inactivation, iron accumulation and dopamine depletion were significantly attenuated in transgenic mice overexpressing mitochondrial Sod2 and exacerbated in partial deficient Sod2 mice. These results suggest that mitochondrial aconitase may be an important early source of mitochondrial iron accumulation in experimental Parkinson's disease, and that superoxide radical toxicity manifested by oxidative inactivation of mitochondrial aconitase may play a pathogenic role in Parkinson's disease.
Autocrine regulation of nerve growth factor expression by Trk receptors
Authors: Mallei Alessandra , Rabin Stuart J. , Mocchetti Italo
Published: August 2004

Activation of the neurotrophin receptor Trk induces the release of neurotrophins. However, little is known about the ability of released neurotrophins to modulate their own synthesis in an autocrine manner. As a step towards understanding the role of Trk in regulating the synthesis of neurotrophins, we exposed NIH‐3T3 cells expressing TrkA or TrkC receptors to their cognate ligands as well as to GM1, a ganglioside that activates TrkA and TrkC by inducing the release of neurotrophin‐3. Nerve growth factor and neurotrophin‐3 synthesis were then determined by measuring the relative levels of protein and mRNA. TrkA‐expressing cells exposed to human recombinant nerve growth factor exhibited higher levels of nerve growth factor mRNA. Human recombinant neurotrophin‐3 evoked an increase in nerve growth factor mRNA in both TrkA and TrkC‐expressing cells. GM1 elicited a time‐dependent increase in nerve growth factor protein and mRNA in NIH‐3T3 cells expressing TrkA or TrkC receptor but not in wild‐type cells. Surprisingly, GM1 failed to change neurotrophin‐3 levels. The ability of GM1 to increase nerve growth factor mRNA levels was blocked by TrkC‐IgG but not by TrkB‐IgG receptor body. These data suggest that released neurotrophin‐3 may activate a positive autocrine loop of nerve growth factor synthesis by Trk activation.
Nogo‐66 and myelin‐associated glycoprotein (MAG) inhibit the adhesion and migration of Nogo‐66 receptor expressing human glioma cells
Authors: Liao Hong , Duka Tetyana , Teng Felicia Y. H. , Sun Li , Bu Wen‐yu , Ahmed Sohail , Tang Bor Luen , Xiao Zhi‐Cheng
Published: August 2004

Malignant gliomas are common and aggressive brain tumours associated with significant morbidity and mortality. We showed in this report that substratum adherence and migration by human U87MG glioma cells in culture were significantly attenuated by the extracellular domains of Nogo‐A (Nogo‐66) and the myelin‐associated glycoprotein (MAG). U87MG cells contained significant amounts of endogenous Nogo‐66 receptor (NgR), and treatment of the cells with phosphatidylinositol‐specific phospholipase C (PI‐PLC) or NgR antibodies resulted in an increase in their ability to adhere to, or migrate through, Nogo‐66‐ and MAG‐coated substrates. Nogo‐66 and MAG may therefore modulate glioma growth and migration by acting through the NgR, a phenomenon that has potential therapeutic implications.
Differential regulation of dopamine D1 and D2 signaling by nicotine in neostriatal neurons
Authors: Hamada Miho , Higashi Hideho , Nairn Angus C. , Greengard Paul , Nishi Akinori
Published: August 2004

Nicotine, acting on nicotinic acetylcholine receptors (nAChRs) expressed at pre‐synaptic dopaminergic terminals, has been shown to stimulate the release of dopamine in the neostriatum. However, the molecular consequences of pre‐synaptic nAChR activation in post‐synaptic neostriatal neurons are not clearly understood. Here, we investigated the effect of nAChR activation on dopaminergic signaling in medium spiny neurons by measuring phosphorylated DARPP‐32 (dopamine‐ and cAMP‐regulated phosphoprotein of Mr 32 kDa) at Thr34 (the PKA‐site) in mouse neostriatal slices. Nicotine produced dose‐dependent responses, with a low concentration (1 µm) causing a sustained decrease in DARPP‐32 Thr34 phosphorylation and a high concentration (100 µm) causing a transient increase in DARPP‐32 Thr34 phosphorylation. Depending on the concentration of nicotine, either dopamine D2 or D1 receptor signaling was predominantly activated. Nicotine at a low concentration (1 µm) activated dopamine D2 receptor signaling in striatopallidal/indirect pathway neurons, likely by activating α4β2* nAChRs at dopaminergic terminals. Nicotine at a high concentration (100 µm) activated dopamine D1 receptor signaling in striatonigral/direct pathway neurons, likely by activating (i) α4β2* nAChRs at dopaminergic terminals and (ii) α7 nAChRs at glutamatergic terminals, which, by stimulating the release of glutamate, activated NMDA/AMPA receptors at dopaminergic terminals. The differential effects of low and high nicotine concentrations on D2‐ and D1‐dependent signaling pathways in striatal neurons may contribute to dose‐dependent actions of this drug of abuse.
Arachidonic acid‐induced carbon‐centered radicals and phospholipid peroxidation in cyclo‐oxygenase‐2‐transfected PC12 cells
Authors: Jiang Jianfei , Borisenko Grigory G. , Osipov Anatoly , Martin Ian , Chen Renwu , Shvedova Anna A. , Sorokin Andrey , Tyurina Yulia Y. , Potapovich Alla , Tyurin Vladimir A. , Graham Steven H. , Kagan Valerian E.
Published: August 2004

Cyclo‐oxygenase‐2 (COX‐2) is believed to induce neuronal oxidative stress via production of radicals. While oxygen radicals are not directly involved in COX‐2‐catalytic cycle, superoxide anion radicals have been repeatedly reported to play a critical role in COX‐2‐associated oxidative stress. To resolve the controversy, we characterized production of free radicals in PC12 cells in which COX‐2 expression was manipulated either genetically or by direct protein transfection and compared them with those generated by a recombinant COX‐2 in a cell‐free system. Using spin‐traps α‐(4‐pyridyl‐1‐oxide)‐N‐t‐butylnitrone, 5,5‐dimethyl‐1‐pyrroline‐N‐oxide and 4‐((9‐acridinecarbonyl) amino)‐2,2,6,6‐ tetramethylpiperidine‐1‐oxyl (Ac‐Tempo), we observed arachidonic acid (AA)‐dependent production of carbon‐centered radicals by heme‐reconstituted recombinant COX‐2. No oxygen radicals or thiyl radicals have been detected. COX‐2 also catalyzed AA‐dependent one‐electron co‐oxidation of ascorbate to ascorbate radicals. Next, we used two different approaches of COX‐2 expression in cells, PCXII cells which express isopropyl‐1‐thio‐β‐d‐galactopyranoside inducible COX‐2, and PC12 cells transfected with COX‐2 using a protein delivery reagent, Chariot. In both models, COX‐2‐dependent AA‐induced generation of carbon‐centered radicals was documented using spin‐traps and Ac‐Tempo. No oxygen radical formation was detected in COX‐2‐transfected cells by either spin‐traps or fluorogenic probe, dihydroethidium. In the presence of ascorbate, AA‐induced COX‐2‐dependent ascorbate radicals were detected. AA caused a significant and selective oxidation of one of the major phospholipids, phosphatidylserine (PS). PS was not a direct substrate for COX‐2 but was co‐oxidized in the presence of AA. The radical generation and PS oxidation were inhibited by COX‐2 inhibitors, niflumic acid, nimesulide, or NS‐398. Thus, COX‐2 generated carbon‐centered radicals but not oxygen radicals or thiyl radicals are responsible for oxidative stress in AA‐challenged PC12 cells overexpressing COX‐2.
S. aureus‐dependent microglial activation is selectively attenuated by the cyclopentenone prostaglandin 15‐deoxy‐Δ12,14‐ prostaglandin J2 (15d‐PGJ2)
Authors: Kielian Tammy , McMahon Meredith , Bearden Edward D. , Baldwin Aaron C. , Drew Paul D , Esen Nilufer
Published: August 2004

Microglial activation is a hallmark of brain abscess. The continual release of proinflammatory mediators by microglia following bacterial challenge may contribute, in part, to the destruction of surrounding normal tissue characteristic of brain abscess. Therefore, attenuating chronic microglial activation during the course of CNS bacterial infections may have therapeutic benefits. The purpose of this study was to evaluate the ability of the natural peroxisome proliferator‐activated receptor (PPAR)‐γ agonist 15‐deoxy‐Δ12,14‐ prostaglandin J2 (15d‐PGJ2) to modulate microglial activation in response to Staphylococcus aureus, one of the main etiologic agents of brain abscess in humans. 15d‐PGJ2 was a potent inhibitor of proinflammatory cytokine (IL‐1β, TNF‐α, IL‐12 p40) and CC chemokine (MIP‐1β, MCP‐1) production in primary microglia, but had no effect upon the expression of select CXC chemokines (MIP‐2, KC). 15d‐PGJ2 also selectively inhibited the S. aureus‐dependent increase in microglial TLR2, CD14, MHC class II, and CD40 expression, whereas it had no effect on the co‐stimulatory molecules CD80 and CD86. Microarray analysis revealed additional inflammatory mediators modulated by 15d‐PGJ2 in primary microglia following S. aureus exposure, the majority of which were chemokines. These results suggest that suppressing microglial activation through the use of 15d‐PGJ2 may lead to the sparing of damage to normal brain parenchyma that often results from brain abscess.
An anti‐CD11d integrin antibody reduces cyclooxygenase‐2 expression and protein and DNA oxidation after spinal cord injury in rats
Authors: Bao Feng , Chen Yuhua , Dekaban Gregory A. , Weaver Lynne C.
Published: August 2004

Our studies have shown that treatment with a monoclonal antibody (mAb) against the CD11d subunit of the leukocyte integrin CD11d/CD18 after spinal cord injury (SCI) decreases intraspinal inflammation, myeloperoxidase activity, lipid peroxidation and protein nitration, improving neurological function in rats. Using severe clip compression SCI in the rat, immunohistochemistry and western blotting were employed to assess the effects of an anti‐CD11d mAb treatment on spinal cord cyclooxygenase‐2 (COX‐2) expression, formation of 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG, a marker of RNA and DNA oxidation) and protein carbonylation (a marker of protein oxidation). We also assessed treatment effects on the expression of apurinic/apyrimidinic endonuclease (redox effector factor‐1, APE/Ref‐1), a multifunctional enzyme involved in the base excision repair of apurinic/apyrimidinic sites in DNA. The expression of COX‐2 and formation of 8‐OHdG and protein carbonyl groups were increased after SCI while APE/Ref‐1 expression was decreased. Anti‐CD11d mAb treatment clearly attenuated COX‐2 expression and 8‐OHdG and protein carbonyl formation and rescued APE/Ref‐1 expression after SCI. This study suggests that anti‐CD11d mAb treatment significantly reduces intraspinal free radical formation after SCI, thereby reducing protein and DNA oxidative damage. These effects likely underlie tissue preservation and improved neurological function resulting from the mAb treatment.
Apolipoprotein E modulates γ‐secretase cleavage of the amyloid precursor protein
Authors: Irizarry Michael C. , Deng Amy , Lleo Alberto , Berezovska Oksana , Von Arnim Christine A. F. , Martin‐Rehrmann Matthew , Manelli Arlene , LaDu Mary Jo , Hyman Bradley T. , Rebeck G. William
Published: August 2004

Polymorphisms in the apolipoprotein E (APOE) gene affect the risk of Alzheimer disease and the amount of amyloid β‐protein (Aβ) deposited in the brain. The apoE protein reduces Aβ levels in conditioned media from cells in culture, possibly through Aβ clearance mechanisms. To explore this effect, we treated multiple neural and non‐neural cell lines for 24 h with apoE at concentrations similar to those found in the cerebrospinal fluid (1–5 µg/mL). The apoE treatment reduced Aβ40 by 60–80% and Aβ42 to a lesser extent (20–30%) in the conditioned media. Surprisingly, apoE treatment resulted in an accumulation of amyloid precursor protein (APP)‐C‐terminal fragments in cell extracts and a marked reduction of APP intracellular domain‐mediated signaling, consistent with diminished γ‐secretase processing of APP. All three isoforms of apoE, E2, E3 and E4, had similar effects on Aβ and APP‐C‐terminal fragments, and the effects were independent of the low‐density lipoprotein receptor family. Apolipoprotein E had minimal effects on Notch cleavage and signaling in cell‐based assays. These data suggest that apoE reduces γ‐secretase cleavage of APP, lowering secreted Aβ levels, with stronger effects on Aβ40. The apoE modulation of Aβ production and APP signaling is a potential mechanism affecting Alzheimer disease risk.