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Using a multi-user desktop-based virtual reality system to recreate the São Miguel das Missões ruins.

This paper presents a project initiated back in 1999, in which Virtual Reality is applied in order to create a virtual community over the Internet. The desktop-based multi-user virtual reality system recreates a three-dimensional environment based on photogrammetric maps from the São Miguel das Missões church ruins. The ruins correspond to one of the Jesuit Mission (settlement) which was active in the south of Brazil in the 17th and 18th centuries. It has a great importance to the local region in terms of cultural, historic, and tourist aspects. It has also been inscribed in the UNESCO's world heritage list since 1983. This electronic mock-up allows several interactive operations such as community chats, electronic message exchanging, message boards, walking-through, discussion groups, and embedding of other media such as movies, sound, and html pages. The only requirement necessary to access the community is a web browser powered with any Virtual Reality Modeling Language (VRML) plug-in freely available over the Internet. It is expected that such a solution improves the conservation and dissemination of the Brazilian historic patrimony, congregating history, art, and tourist information in one place on the Internet.

Humans↗

Impairment on the hippocampal-dependent virtual Morris water task in schizophrenia.

Traditional neuropsychological tests of visual and verbal memory have been used to evaluate memory deficits in schizophrenia. However, these tests cannot be used in non-human animal research, which is important for the discovery of treatments that will improve cognition and for study of the etiology of schizophrenia. To help bridge the gap between human and non-human animal research on hippocampal function in schizophrenia, this study sought to characterize the behavioral performance exhibited by patients using the Morris water task (MWT). The MWT has been shown in human and non-human animal studies to be hippocampus-dependent. In the virtual MWT, human subjects navigate a computer-generated on-screen environment to escape from the "water" by locating a platform. Patients with schizophrenia and controls performed two versions of the virtual MWT: a hippocampal-dependent hidden-platform version, relying on allocentric navigational abilities, and a non-hippocampal-dependent visible-platform version, relying on cued-navigational abilities. Patients traveled further and took longer to find the hidden platform over training blocks and spent less time in the correct quadrant during a probe trial. There was no deficit in the visible-platform condition. These findings identify a behavioral impairment on a hippocampal-dependent task in schizophrenia and support using the MWT in testing animal models of schizophrenia.

Adult↗

[Discrepancy between surgeon's binocular parallax perception and manipulation in the neurosurgical operation].

The application of virtual reality (VR) to the neurosurgical field has been increasing recently, however, the relation between the surgeon and the VR environment is rarely studied. We examined the trajectory of a surgical instrument during manipulation of a virtual object using a video-see-through microscope and a neurosurgical navigator (CANS Navigator) to find better surgeon-microscope interface. A resin cylindrical phantom was produced representing the surgical field, which included two 3 dimensionally arranged small spheres and a virtual 'gate'. The phantom was fixed and set under the microscope with a skull clamp mimicking conditions in an ordinary craniotomy. Firstly, the binocular parallax perception under microscope was examined. Experienced and inexperienced neurosurgeons were asked to learn the position of the virtual 'gate' for 3 minutes. Then, after 5 minutes to point with the navigator probe (suction tube), under various conditions; under the naked eyes, under the microscope, under the navigator without observing the phantom, and under the microscope with picture in picture (PIP) display of the navigational image. The positions of the suction tube were recorded at real time into the navigator for later analysis. Secondly, the task performance in this VR environment was studied by analyzing the trajectory of the suction tube from one sphere to the other sphere passing the virtual 'gate' under various conditions. A significant difference in pointing precision between experienced and inexperienced neurosurgeons was able to be observed only under microscope. This difference was mainly derived from overestimation of the depth of the virtual 'gate' by the inexperienced neurosurgeons. Among the above conditions, pointing under the microscope with PIP was able to be performed the most precisely and the most promptly. This study disclosed the presence of stereoscopic distortion in the microscope. The PIP display of the navigational image in the microscopic view remarkably improved the task performance, which could be accounted for by the correction of the somewhat distorted binocular parallax perception under the neurosurgical microscope by the provision of another visual key.

Brain↗

Colorectal cancer as a disease of the environment.

Colorectal cancer is common in North America and Europe but is virtually unknown among the native population of sub-Saharal Africa. Within the continent of Europe, colon cancer incidence varies fourfold between cancer registry regions. Within the United Kingdom, colon cancer is, and has been for 70 years, commoner in Scotland than in England and Wales. In Scotland, the disease is one-third commoner in the north of the country than in the south. Colorectal cancer risk is determined by local environmental conditions within the bowel: these are determined to a large extent by diet which in its turn is dictated by environmental conditions, both geographic and economic. Cancer as a group of diseases which causes 40% of all deaths, is a disease of the environment, with colorectal cancer the best example of this in a common tumour.

Africa↗

The Effect of Game-Based Virtual Reality Rehabilitation and Its Impact on Upper Extremity Function After Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) often results in prolonged recovery and limited shoulder function. Conventional physical therapy rehabilitation programs require sustained patient engagement; however, adherence is frequently low. Game-based virtual reality (VR) offers an interactive and engaging environment that may enhance rehabilitation outcomes. OBJECTIVE: To evaluate the effect of a game-based VR program on the function of the upper limb in patients following ARCR. METHODS: A randomized controlled trial was conducted with patients who underwent ARCR. Participants were randomized into two groups: game-based VR or conventional rehabilitation. Outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand score, pain severity by the Numerical Pain Rating Scale, range of motion measures, and muscle strength testing. Assessments were performed at baseline and at 6 weeks and 12 weeks post surgery. RESULTS: Results have shown significant within-group improvements in pain, function, range of motion, and isometric muscle strength across all time points (P < 0.05). Between-group analysis revealed greater improvements in pain, function, flexion range, and abduction and external rotation strength in the experimental group at both time points (P < 0.05). Abduction range improved significantly only at 12 weeks (P = 0.02), whereas external rotation range showed no significant difference between groups at either time point (P > 0.05). CONCLUSION: The findings indicate that integrating game-based VR rehabilitation provides additional benefits over conventional therapy in improving pain and upper extremity function following ARCR. These findings support the use of VR as an effective alternative to the conventional rehabilitation for postoperative rehabilitation.

Humans↗

Different brain correlates for watching real and virtual hand actions.

We investigated whether observation of actions reproduced in three-dimensional virtual reality would engage perceptual and visuomotor brain processes different from those induced by the observation of real hand actions. Participants were asked to passively observe grasping actions of geometrical objects made by a real hand or by hand reconstructions of different quality in 3D virtual reality as well as on a 2D TV screen. We found that only real actions in natural environment activated a visuospatial network including the right posterior parietal cortex. Observation of virtual-reality hand actions engaged prevalent visual perceptual processes within lateral and mesial occipital regions. Thus, only perception of actions in reality maps onto existing action representations, whereas virtual-reality conditions do not access the full motor knowledge available to the central nervous system.

Adult↗

Using multimedia virtual patients to enhance the clinical curriculum for medical students.

Changes in the environment in which clinical medical education takes place in the United States has profoundly affected the quality of the learning experience. A shift to out-patient based care, minimization of hospitalization time, and shrinking clinical revenues has changed the teaching hospital or "classroom" to a degree that we must develop innovative approaches to medical education. One solution is the Virtual Patient Project. Utilizing state-of-the-art computer-based multimedia technology, we are building a library of simulated patient encounters that will serve to fill some of the educational gaps that the current health care system has created. This project is part of a newly formed and unique organization, the Harvard Medical School-Beth Israel Deaconess Mount Auburn Institute for Education and Research (the Institute), which supports in-house educational design, production, and faculty time to create Virtual Patients. These problem-based clinical cases allow the medical student to evaluate a patient at initial presentation, order diagnostic tests, observe the outcome and obtain context-sensitive feedback through a computer program designed at the Institute. Multimedia technology and authoring programs have reached a level of sophistication to allow content experts (the teaching faculty) to design and create the majority of the program themselves and to allow students to adapt the program to their individual learning needs.

Computer Simulation↗

Toxicity testing of crude oil and related compounds using early life stages of the crimson-spotted rainbowfish (Melanotaenia fluviatilis).

The toxicity of petroleum hydrocarbons to marine aquatic organisms has been widely investigated; however, the effects on freshwater environments have largely been ignored. In the Australian freshwater environment, the potential impacts of petroleum hydrocarbons are virtually unknown. The toxicity of crude oil and related compounds were measured in the sensitive early life stages of the crimson-spotted rainbowfish (Melanotaenia fluviatilis). Waterborne petroleum hydrocarbons crossed the chorion of embryonic rainbowfish, reducing survival and hatchability. Acute exposures resulted in developmental abnormalities at and above 0.5 mg/L total petroleum hydrocarbons (TPH). Deformities included pericardial edema, disturbed axis formation, and abnormal jaw development. When assessing the acute toxicities of the water-accommodated fraction (WAF) of crude oil, dispersants, dispersant-oil mixtures, and naphthalene to larval rainbowfish, the lowest to highest 96-h median lethal concentrations for day of hatch larvae were naphthalene (0.51 mg/L), dispersed crude oil WAF (DCWAF)-9527 (0.74 mg/L TPH), WAF (1.28 mg/L TPH), DCWAF-9500 (1.37 mg/L TPH), Corexit 9500 (14.5 mg/L TPH), and Corexit 9527 (20.1 mg/L). Using naphthalene as a reference toxicant, no differences were found between the sensitivities of larval rainbowfish collected from adults exposed to petroleum hydrocarbons during embryonic development and those collected from unexposed adults.

Animals↗

Freedom through a single switch: coping and communicating with artificial ventilation.

Challenging clients often stretch the limits of the imagination in terms of developing creative technologies to allow access to computers, communication devices and environmental controls. This paper provides a description of an innovative system that enables clients with motor neurone disease/amyotrophic lateral sclerosis (MND/ALS), on full ventilatory support and virtually no movement, to communicate and manipulate their environments, through the use of a myoelectrically controlled switch.

Amyotrophic Lateral Sclerosis↗

Chemotaxis in Bacillus subtilis: how bacteria monitor environmental signals.

Virtually all organisms have means of monitoring their environment and making use of information gained to aid their survival. Many organisms, from bacteria to animals, move from place to place and can alter their movements. Chemotaxis is a signal transduction system found in motile bacteria that allows them to sense changes in the concentrations of various extracellular compounds and change their swimming behavior in a way that moves them toward more favorable environments. Chemotaxis is the most ancient sensory-motor process in nature. For years, studies of enteric bacteria, such as Escherichia coli and Salmonella typhimurium, have served as the paradigm for understanding this process on a molecular level. Recent studies on the gram-positive bacterium, Bacillus subtilis, and other bacteria, suggest that a slightly more complex system may be ancestral to that of the more extensively studied enterics. Aspects of chemotaxis that are unique to B. subtilis include a more complex adaptation system, with protein-protein methyl group transfer, chemotaxis proteins having no counterparts in E. coli, and a very extensive repertoire of repellents that are sensed at very low concentrations by receptors.

Bacillus subtilis↗

The controlled introduction of multiple negative charge at single amino acid sites in subtilisin Bacillus lentus.

The use of methanethiosulfonates as thiol-specific modifying reagents in the strategy of combined site-directed mutagenesis and chemical modification allows virtually unlimited opportunities for creating new protein surface environments. As a consequence of our interest in electrostatic manipulation as a means of tailoring enzyme activity and specificity, we have adopted this approach for the controlled incorporation of multiple negative charges at single sites in the representative serine protease, subtilisin Bacillus lentus (SBL). A series of mono-, di- and triacidic acid methanethiosulfonates were synthesized and used to modify cysteine mutants of SBL at positions 62 in the S2 site, 156 and 166 in the S1 site and 217 in the S1' site. Kinetic parameters for these chemically modified mutant (CMM) enzymes were determined at pH 8.6 under conditions which ensured complete ionization of the unnatural amino acid side-chains introduced. The presence of up to three negative charges in the S1, S1' and S2 subsites of SBL resulted in up to 11-fold lowered activity, possibly due to interference with oxyanion stabilization of the transition state of the hydrolytic reactions catalyzed. Each unit increase in negative charge resulted in a raising of K(M) and a reduction of k(cat). However, no upper limit was observed for increases in K(M), whereas decreases in k(cat) reached a limiting value. Comparison with sterically similar but uncharged CMMs revealed that electrostatic effects of negative charges at positions 62, 156 and 217 are detrimental, but are beneficial at position 166. These results indicate that the ground-state binding of SBL to the standard substrate, Suc-AAPF-pNA, to SBL is reduced, but without drastic attenuation of catalytic efficiency, and show that SBL tolerates high levels of charge at single sites.

Amino Acids↗

Altering the specificity of subtilisin Bacillus lentus through the introduction of positive charge at single amino acid sites.

The use of methanethiosulfonates as thiol-specific modifying reagents in the strategy of combined site-directed mutagenesis and chemical modification allows virtually unlimited opportunities for creating new protein surface environments. As a consequence of our interest in electrostatic manipulation as a means of tailoring enzyme activity and specificity, we have recently adopted this approach for the controlled incorporation of multiple negative charges at single sites in the representative serine protease, subtilisin Bacillus lentus (SBL). We now describe the use of this strategy to introduce multiple positive charges. A series of mono-, di- and triammonium methanethiosulfonates were synthesized and used to modify cysteine mutants of SBL at positions 62 in the S2 site, 156 and 166 in the S1 site and 217 in the S1' site. Kinetic parameters for these chemically modified mutants (CMM) enzymes were determined at pH 8.6. The presence of up to three positive charges in the S1, S1' and S2 subsites of SBL resulted in up to 77-fold lowered activity, possibly due to interference with the histidinium ion formed in the transition state of the hydrolytic reactions catalyzed.

Amino Acids↗

Single-molecule mechanics of mussel adhesion.

The glue proteins secreted by marine mussels bind strongly to virtually all inorganic and organic surfaces in aqueous environments in which most adhesives function poorly. Studies of these functionally unique proteins have revealed the presence of the unusual amino acid 3,4-dihydroxy-L-phenylalanine (dopa), which is formed by posttranslational modification of tyrosine. However, the detailed binding mechanisms of dopa remain unknown, and the chemical basis for mussels' ability to adhere to both inorganic and organic surfaces has never been fully explained. Herein, we report a single-molecule study of the substrate and oxidation-dependent adhesive properties of dopa. Atomic force microscopy (AFM) measurements of a single dopa residue contacting a wet metal oxide surface reveal a surprisingly high strength yet fully reversible, noncovalent interaction. The magnitude of the bond dissociation energy as well as the inability to observe this interaction with tyrosine suggests that dopa is critical to adhesion and that the binding mechanism is not hydrogen bond formation. Oxidation of dopa, as occurs during curing of the secreted mussel glue, dramatically reduces the strength of the interaction to metal oxide but results in high strength irreversible covalent bond formation to an organic surface. A new picture of the interfacial adhesive role of dopa emerges from these studies, in which dopa exploits a remarkable combination of high strength and chemical multifunctionality to accomplish adhesion to substrates of widely varying composition from organic to metallic.

Adhesiveness↗

Transformation of mammalian cells with an amplifiable dominant-acting gene.

We have transferred a mutant hamster gene coding for an altered dihydrofolate reductase to wild-type cultured mouse cells by using total genomic DNA from methotrexate-resistant Chinese hamster ovary A29 cells as donor. By demonstrating the presence of hamster gene sequences in transformants we have provided direct evidence for gene transfer. Transformants selected for increased resistance to methotrexate contain increased amounts of the newly transferred gene. We have used this mutant dhfr gene to introduce the Escherichia coli antibiotic resistance plasmid pBR322 into animal cells. Amplification of the dhfr sequences results in amplification of the pBR322 sequences as well. The use of this gene may allow the introduction and amplification of virtually any genetic element in various new cellular environments.

Animals↗

Gene-culture coevolution of complex social behavior: human altruism and mate choice.

The hypothesis is examined that genes bias the development of complex social behavior in one direction over alternatives. Studies of altruism and political attitudes in twins estimate that approximately 50% of the variance is associated with direct genetic inheritance, virtually 0% with the twin's common family environment, and the remainder with each twin's specific environment. Studies of human marriages show that spouses choose each other on the basis of similarity, assorting on the most genetically influenced of a set of homogeneous attributes. These data imply a genetic canalization of social influences such that, within the constraints allowed by the total spectrum of cultural alternatives, people create environments maximally compatible with their genotypes.

Altruism↗

Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity.

Hypertonicity (most often present as high salinity) is stressful to the cells of virtually all organisms. Cells survive in a hypertonic environment by increasing the transcription of genes whose products catalyze cellular accumulation of compatible osmolytes. In mammals, the kidney medulla is normally hypertonic because of the urinary concentrating mechanism. Cellular accumulation of compatible osmolytes in the renal medulla is catalyzed by the sodium/myo-inositol cotransporter (SMIT), the sodium/chloride/betaine cotransporter, and aldose reductase (synthesis of sorbitol). The importance of compatible osmolytes is underscored by the necrotic injury of the renal medulla and subsequent renal failure that results from the inhibition of SMIT in vivo by administration of a specific inhibitor. Tonicity-responsive enhancers (TonE) play a key role in hypertonicity-induced transcriptional stimulation of SMIT, sodium/chloride/betaine cotransporter, and aldose reductase. We report the cDNA cloning of human TonE binding protein (TonEBP), a transcription factor that stimulates transcription through its binding to TonE sequences via a Rel-like DNA binding domain. Western blot and immunohistochemical analyses of cells cultured in hypertonic medium reveal that exposure to hypertonicity elicits slow activation of TonEBP, which is the result of an increase in TonEBP amount and translocation to the nucleus.

Amino Acid Sequence↗

Knowledge-based potential defined for a rotamer library to design protein sequences.

A knowledge-based potential for a rotamer library was developed to design protein sequences. Protein side-chain conformations are represented by 56 templates. Each of their fitness to a given structural site-environment is evaluated by a combined function of the three knowledge-based terms, i.e. two-body side-chain packing, one-body hydration and local conformation. The number of matches between the native sequence and the structural site-environment in the database and that of the virtually settled mismatches, counted in advance, were transformed into the energy scores. In the best-14 test (assessment for the reproduction ability of the native rotamer on its structural site within a quarter of 56 fitness rank positions), the structural stability analysis on mutants of human and T4 lysozymes and the inverse-folding search by a structure profile against the sequence database, this function performs better than the function deduced with the conventional normalization and our previously developed function. Targeting various structural motifs, de novo sequence design was conducted with the function. The sequences thus obtained exhibit reasonable molecular masses and hydrophobic/hydrophilic patterns similar to the native sequences of the target and act as if they were the homologs to the target proteins in BLASTP search. This significant improvement is discussed in terms of the reference state for normalization and the crucial role of short-range repulsion to prohibit residue bumps.

Amino Acid Sequence↗

Functional anatomy of object recognition in humans: evidence from positron emission tomography and functional magnetic resonance imaging.

The ability to recognize elements of the environment as familiar objects, events, or classes underlies virtually all human cognition. Positron emission tomography and functional magnetic resonance imaging studies of the recognition of visually presented objects suggest that several brain areas crucially support this function. However, a review of these findings reveals great variability in the cortical localization of object recognition in humans. Although there is converging evidence for the importance of the temporal and occipitotemporal cortex in object recognition, a consistent picture of the functional organization within these areas and their relation to function in other cortical regions has not yet emerged from brain imaging studies.

Arousal↗