Interactive Graphics in Industry: The Early Days.

Computer graphics has a long history. Industrial organizations and laboratories drove significant improvements as they adapted and assembled basic capabilities into complex interactive applications. Of particular concern in the early days was providing interactive 3-D applications for computer-aided design and engineering. This article describes the experience of two early industry practitioners who built successful 1970s interactive 3-D systems.

Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors.

Chondroitin sulfate proteoglycans (CSPGs) are a family of extracellular matrix molecules with various functions in regulating tissue morphogenesis, cell division, and axon guidance. A number of CSPGs are highly upregulated by reactive glial scar tissues after injuries and form a strong barrier for axonal regeneration in the adult vertebrate CNS. Although CSPGs may negatively regulate axonal growth via binding and altering activity of other growth-regulating factors, the molecular mechanisms by which CSPGs restrict axonal elongation are not well understood. Here, we identified a novel receptor mechanism whereby CSPGs inhibit axonal growth via interactions with neuronal transmembrane leukocyte common antigen-related phosphatase (LAR). CSPGs bind LAR with high affinity in transfected COS-7 cells and coimmunoprecipitate with LAR expressed in various tissues including the brain and spinal cord. CSPG stimulation enhances activity of LAR phosphatase in vitro. Deletion of LAR in knock-out mice or blockade of LAR with sequence-selective peptides significantly overcomes neurite growth restrictions of CSPGs in neuronal cultures. Intracellularly, CSPG-LAR interaction mediates axonal growth inhibition of neurons partially via inactivating Akt and activating RhoA signals. Systemic treatments with LAR-targeting peptides in mice with thoracic spinal cord transection injuries induce significant axon growth of descending serotonergic fibers in the vicinity of the lesion and beyond in the caudal spinal cord and promote locomotor functional recovery. Identification of LAR as a novel CSPG functional receptor provides a therapeutic basis for enhancing axonal regeneration and functional recovery after CNS injuries in adult mammals.

A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons.

Ibuprofen is a nonsteroidal anti-inflammatory drug widely used to relieve pain and inflammation in many disorders via inhibition of cyclooxygenases. Recently, we have demonstrated that ibuprofen inhibits intracellular signaling of RhoA and promotes significant axonal growth and functional recovery following spinal cord lesions in rodents. In addition, another study suggests that ibuprofen reduces generation of amyloid-beta42 peptide via inactivation of RhoA signaling, although it may also regulate amyloid-beta42 formation by direct inhibition of the gamma-secretase complex. The molecular mechanisms by which ibuprofen inhibits the RhoA signal in neurons, however, remain unclear. Here, we report that the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) is essential for coupling ibuprofen to RhoA inhibition and subsequent neurite growth promotion in neurons. Ibuprofen activates PPARgamma in neuron-like PC12 and B104 cells. Activation of PPARgamma with traditional agonists mimics the RhoA-inhibiting properties of ibuprofen in PC12 cells and, like ibuprofen, promotes neurite elongation in primary cultured neurons exposed to axonal growth inhibitors. Protein knockdown with small interfering RNA specific for PPARgamma blocks RhoA suppression of PPARgamma agonists in PC12 cells. Moreover, the effect of ibuprofen on RhoA activity and neurite growth in neuronal cultures is prevented by selective PPARgamma inhibition. These findings support that PPARgamma plays an essential role in mediating the RhoA-inhibiting effect of ibuprofen. Elucidation of the novel molecular mechanisms linking ibuprofen to RhoA inhibition may provide additional therapeutic targets to the disorders characterized by RhoA activation, including spinal cord injuries and Alzheimer's disease.

Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS.

Axonal regeneration is minimal after CNS injuries in adult mammals and medical treatments to recover neurological deficits caused by axon disconnection are extremely limited. The failure of axonal elongation is principally attributed to the nonpermissive environment and reduced intrinsic growth capacity. In this report, we studied the role of glycogen synthase kinase-3 (GSK-3) inactivation on neurite and axon growth from adult neurons via combined in vitro and in vivo approaches. We found that the major CNS inhibiting substrates including chondroitin sulfate proteoglycans could inactivate protein kinase B (Akt) and activate GSK-3beta signals in neurons. GSK-3 inactivation with pharmacologic inhibitors enhances neurite outgrowth of dorsal root ganglion neurons derived from adult mice or cerebellar granule neurons from postnatal rodents cultured on CNS inhibitors. Application of GSK-3 inhibitors stimulates axon formation and elongation of mature neurons whether in presence or absence of inhibitory substrates. Systemic application of the GSK-3 inhibitor lithium to spinal cord-lesioned rats suppresses the activity of this kinase around lesion. Treatments with GSK-3 inhibitors including a clinical dose of lithium to rats with thoracic spinal cord transection or contusion injuries induce significant descending corticospinal and serotonergic axon sprouting in caudal spinal cord and promote locomotor functional recovery. Our studies suggest that GSK-3 signal is an important therapeutic target for promoting functional recovery of adult CNS injuries and that administration of GSK-3 inhibitors may facilitate the development of an effective treatment to white matter injuries including spinal cord trauma given the wide use of lithium in humans.

Optimal number of beams for stereotactic body radiotherapy of lung and liver lesions.

PURPOSE: The aim of this study was to determine the optimal number of coplanar and noncoplanar external beams in the setting of stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Spherical targets were delineated within 2 separate extracranial sites, the lung and liver, with diameters varying from 2 cm to 7 cm to cover the range of volumes used in SBRT. Treatment plans were created for all target volumes using 5 to 15 geometrically optimized coplanar and noncoplanar conformal beams. Dose gradient and normal tissue complication probability (NTCP) were evaluated for each set of beam configurations and for each target size. RESULTS: For all lung and liver target volumes, the dose gradient improved with an increase in beam number from 5 to 15 for both coplanar and noncoplanar beam configurations. NTCP decreased as the beam number increased from 5 to 9 beams for all target sizes for both coplanar and noncoplanar beams. There is no significant improvement in NTCP when more than 9 beams were used for treatment planning regardless of target size. CONCLUSION: Based on dosimetric criteria, the optimal number of external beams is 13 to 15 for SBRT using either coplanar or noncoplanar beam bouquets. Simple biologic models indicate that the optimal number of beams is 9 for SBRT of lung and liver lesions >2 cm, whereas smaller lesions may benefit from plans using up to 13 beams.

Acquiring laparoscopic manipulative skills: a virtual tissue dissection training module.

Virtual environments for training manipulative skills in laparoscopic surgery are now well established as research areas. Tissue dissection however has not yet been adequately addressed. We have developed a virtual training module in which the task is to dissect a 3D tissue model using a simulated L-hook. Three metrics have been designed to assess performance. 1) Total deviation of actual cut path from the drawn path. 2) Total contact time between the instrument and tissue. 3) Contact discontinuity. The objective of the research was to design a basic tissue dissection module to train, in part, laparoscopic manipulative skills.

Reference values of pulmonary function tests for Canadian Caucasians.

A multicentre, cross-sectional study was carried out in six centres across Canada to establish a national standard for pulmonary function tests using healthy, lifetime nonsmokers, with each centre aiming to test 10 men and 10 women from each decade from 20 to 80 years of age. Data from each centre were used to derive prediction equations for each centre, and pooled data from all centres (total: 327 women and 300 men) were used to derive Canadian predicted equations. The predictive models were compared with three widely used published models for selected tests. It was found that, in general, the equations modelled for each centre could be replaced by the models obtained when pooling all data (Canadian model). Comparisons with the published references showed good agreement and similar slopes for most tests. The results suggest that pulmonary function test results obtained from different centres in Canada were comparable and that standards currently used remain valid for Canadian Caucasians.

Geometrically based optimization for extracranial radiosurgery.

For static beam conformal intracranial radiosurgery, geometry of the beam arrangement dominates overall dose distribution. Maximizing beam separation in three dimensions decreases beam overlap, thus maximizing dose conformality and gradient outside of the target volume. Webb proposed arrangements of isotropically convergent beams that could be used as the starting point for a radiotherapy optimization process. We have developed an extracranial radiosurgery optimization method by extending Webb's isotropic beam arrangements to deliverable beam arrangements. This method uses an arrangement of N maximally separated converging vectors within the space available for beam delivery. Each bouquet of isotropic beam vectors is generated by a random sampling process that iteratively maximizes beam separation. Next, beam arrangement is optimized for critical structure avoidance while maintaining minimal overlap between beam entrance and exit pathways. This geometrically optimized beam set can then be used as a template for either conformal beam or intensity modulated extracranial radiosurgery. Preliminary results suggest that using this technique with conformal beam planning provides high plan conformality, a steep dose gradient outside of the tumour volume and acceptable critical structure avoidance in the majority of clinical cases.

Automatic measurement of the labyrinth using image registration and a deformable inner ear atlas.

RATIONALE AND OBJECTIVES: This article presents a new method for measuring the shape of the cochlea, vestibule, semi-circular canals, and internal auditory canal using image registration and a deformable inner ear atlas. MATERIALS AND METHODS: Computed tomography images of the inner ear are analyzed by placing them into a common orientation and then registering a digital atlas of the inner ear to the data set. The atlas is deformed from its original shape to match the shape of the inner ear in the computed tomography data set using inverse consistent elastic image registration. This process produces an individualized inner ear atlas containing subject-specific measurements and segmentations of the inner ear anatomy in the target computed tomography data set. The shape measurements include the volume and length of the cochlea, vestibule, semi-circular canals, and internal auditory canal; and the angles between the semi-circular canals. RESULTS: A simulated population of inner ear shapes were generated based on the shape of a real population of inner ear shapes and were used to characterize the measurement error of this method. The deformable atlas was used to measure the shape of the left and right inner ear of six individuals. CONCLUSION: Measurement error for 15 of the 24 measurements of our simulated population had an average error of less than 1% and only one measurement had an average error greater than 2.54%. The deformable human inner ear atlas shows promise as a new method for automatically measuring the shape of the labyrinth.

On defining metrics for assessing laparoscopic surgical skills in a virtual training environment.

One of the key components of any training environment for surgical education is a method that can be used for assessing surgical skills. Traditionally, defining such a method has been difficult and based mainly on observations. However, through advances in modeling techniques and computer hardware and software, such methods can now be developed using combined visual and haptic rendering of a training scene. This paper presents some ideas on how metrics may be defined and used in the assessment of surgical skills in a virtual laparoscopic training environment.