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PubMed2001

A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events.

Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations in medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events.

Adult↗
PubMed1979

Aging, genetics, and the environment: potential of errors introduced into genetic information transfer by metal ions.

Metal ions, which are introduced into living organisms from the environment, are required in every aspect of genetic information transfer. However, the "wrong" metal ion, or even the "right" metal ion in the wrong concentration, can produce deleterious information transfer effects. Metal ions react with nucleic acids in many different ways, and virtually all of these reactions effect major changes in the structure of the nucleic acids. Cellular metal ion concentrations change with age. The effects of such concentration changes on genetic information transfer suggest the possibility that metal ions can influence the aging process. A specific example of such influence is the accumulation in brain cells of aluminum ions, which may have a relationship to Alzheimer's disease.

Aging↗
PubMed2004

Navigating in a virtual three-dimensional maze: how do egocentric and allocentric reference frames interact?

Spatial navigation in the presence of gravity restricts one's displacement to two-dimensional (2D) planes. Therefore, self-motion only includes translations and yaw rotations. In contrast, in weightlessness, one can translate and turn in any direction. In the first experiment, we compared the ability to memorize a virtual three-dimensional (3D) maze after passive exploration in three self-motion conditions, each using a different set of rotations for turning. Subjects indicated which pathway they traversed among four successive corridors presented from an outside perspective. Results showed that exploring in the terrestrial condition (including only yaw rotations, the viewer's virtual body remaining upright) allowed better recognition of the corridor than in the weightless condition (which included pitch and yaw rotations according to the turns), particularly for more complex 3D structures. The more frequently the viewer-defined (egocentric) and the global environment (allocentric) verticals were aligned during exploration, the more easily subjects could memorize the 3D maze, suggesting that simplifying the relationship between the egocentric and allocentric reference frames facilitates spatial updating. Nevertheless, with practice, performance in the weightless condition improved whereas in the natural terrestrial condition performance remained at its initial maximum, indicating that the cognitive processes involved were innate for this particular condition. The second experiment revealed that single rotations in the terrestrial condition must be performed around the body axis in order to obtain optimal spatial updating performance, and that the latter is independent of the conflict with gravity that might favor this condition when one is actually upright. This suggests that although humans can memorize 3D-structured environments their innate neurocognitive functions appear to be specialized for natural 2D navigation.

Adult↗
PubMed2003

Developing a virtual patient record using XML and web-based workflow technologies.

Virtual patient records (VPR) provide a means for integrated access to patient information that may be scattered around different healthcare settings. Within the boundaries of a health district providing all levels of care, this concept can be implemented in a corporate Intranet environment to support longitudinal patient care activities across the participating healthcare providers. In this context, a VPR implementation enables autonomous healthcare providers to operate in a cooperative working environment and apply continuity of care. Workflow systems bring this collaboration and cooperation into effect by automatically routing the medical information needed by authorized actors in a healthcare process. This paper presents a VPR framework that allows integrating geographically dispersed medical information within a health district and enhancing collaboration and coordination of authorized workgroups by means of a web-based workflow system. An implementation of the proposed framework is also presented.

Delivery of Health Care, Integrated↗
PubMed1996

Dynamic structure of the calmodulin-binding domain of the plasma membrane Ca-ATPase in native erythrocyte ghost membranes.

We have used frequency-domain fluorescence resonance energy transfer (FRET) and anisotropy measurements to identify the structural properties of wheat germ calmodulin (CaM) bound to either the plasma membrane Ca-ATPase (PM-Ca-ATPase) in native erythrocyte ghost membranes or a peptide (C25W) that has an identical sequence to the CaM-binding domain on the PM-Ca-ATPase. Cross-linking experiments using benzophenone labeled CaM in conjunction with immunoblots using antibodies specific for either CaM or the PM-Ca-ATPase indicate that one molecule of CaM selectively binds one PM-Ca-ATPase polypeptide chain in native erythrocyte ghost membranes. There are no other proteins in the erythrocyte membrane that bind CaM with high affinity, permitting the measurement of the structural properties of CaM bound to the PM-Ca-ATPase in native erythrocyte ghost membranes. FRET measurements between the fluorophore pyrene maleimide (PMal) located at Cys27 in calcium binding loop I and nitrotyrosine139 in calcium binding loop IV on wheat germ CaM indicate that the average spatial separation and conformational heterogeneity associated with the two opposing globular domains of CaM are virtually identical upon CaM binding to either the PM-Ca-ATPase or C25W. Measurements of the solvent accessibility and segmental rotational dynamics of PMal-CaM bound to either the PM-Ca-ATPase or C25W further indicate that the local environment around the pyrene label located at Cys27 is very similar. However, the overall rotational dynamics of CaM bound to the PM-Ca-ATPase is much slower (phi 2 = 83 +/- 14 ns) than observed when CaM binds C25W (phi 2 = 10.3 +/- 0.5 ns). This implies that CaM is tightly associated with the CaM-binding domain of the PM-Ca-ATPase and that the observed rotational motion of pyrenylmaleimide labeled CaM is characteristic of the global motion of the CaM-binding domain on the PM-Ca-ATPase. The similar conformational heterogeneity and local environment of CaM bound to either the PM-Ca-ATPase or C25W indicates that CaM binds to a contiguous sequence of amino acids on the Ca-ATPase that are analogous to C25W and that there are no significant interactions with other structural elements within the PM-Ca-ATPase. The rate of rotational motion associated with CaM bound to the PM-Ca-ATPase is consistent with hydrodynamic calculation in which the calmodulin-binding domain located at the carboxyl-terminus of the PM-Ca-ATPase has a stable and defined tertiary structure that is independent of the other cytoplasmic domains of the PM-Ca-ATPase.

Animals↗
PubMed1977

Effects of detergents on the conformation of Escherichia coli tRNA as measured by circular dichroism.

The effect of a cationic detergent, lauryl pyridiniumchloride (LPC), and an anionic one, sodium n-octylbenzenesulfonate (SOBS), on the conformation of unfractionated Escherichia coli tRNA was investigated at various molar ratios of detergent to tRNA (D/R) in the presence and absence of Mg2+ and Na+ ions by measuring the circular dichroism (CD) at 265 nm and 340 nm, which reflects conformational change involving base pairs and/or base stacking, and the disymmetry in the vicinity of 4-thiouridylate (4-TU), respectively. In the presence of Mg2+ and Na+ ions, the tRNA retains its native structure even in the presence of high molar ratios of detergent to tRNA (D/R congruent to 40 at 265 nm and D/R congruent to 20 at 340 nm). However, in the absence of these metal ions, the ellipticity at 340 nm was very sensitive to LPC concentration and decreased from 5,600 to nearly--1,600 at 25 degrees C with the increase of D/R ratios up to 20, and a similar decrease in the ellipticity at 340 nm was observed on thermal denaturation. This result suggests that the local environment involving the 4-TU region might be readily influenced by LPC, reflecting a large conformational change. However, no effect was observed in the case of the SOBS: tRNA system. On the other hand, secondary base pairing and/or base stacking structure was virtually invariant on adding both LPC and SOBS even at high D/R ratios in the absence of Mg2+ and Na+ ions.

Benzenesulfonates↗
PubMedDate not supplied

"Virtual" health care organizations and the challenges of improving quality.

This article examines the challenges of improving health care quality continuously within and across "virtual" provider organizations such as independent practice associations and physician-hospital organizations. It draws on recent research and theory about interorganizational networks in other fields to develop recommendations for securing physicians' commitment to quality improvement strategies in today's health care environment.

Cooperative Behavior↗
PubMed2003

Enhancer trapping reveals widespread circadian clock transcriptional control in Arabidopsis.

The circadian clock synchronizes the internal biology of an organism with the environment and has been shown to be widespread among organisms. Microarray experiments have shown that the circadian clock regulates mRNA abundance of about 10% of the transcriptome in plants, invertebrates, and mammals. In contrast, the circadian clock regulates the transcription of the virtually all cyanobacterial genes. To determine the extent to which the circadian clock controls transcription in Arabidopsis, we used in vivo enhancer trapping. We found that 36% of our enhancer trap lines display circadian-regulated transcription, which is much higher than estimates of circadian regulation based on analysis of steady-state mRNA abundance. Individual lines identified by enhancer trapping exhibit peak transcription rates at circadian phases spanning the complete circadian cycle. Flanking genomic sequence was identified for 23 enhancer trap lines to identify clock-controlled genes (CCG-ETs). Promoter analysis of CCG-ETs failed to predict new circadian clock response elements (CCREs), although previously defined CCREs, the CCA1-binding site, and the evening element were identified. However, many CCGs lack either the CCA1-binding site or the evening element; therefore, the presence of these CCREs is insufficient to confer circadian regulation, and it is clear that additional elements play critical roles.

Arabidopsis↗
PubMed1987

Mercury as a health hazard.

Pink disease has virtually disappeared since teething powders were withdrawn. We describe a case in a boy who was exposed to metallic mercury vapour. We discuss the potential health hazard of spilled elemental mercury in the house and the difficulties of removing it from the environment.

Acrodynia↗
PubMed2006

Human melanoma cells express functional receptors for thyroid-stimulating hormone.

We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, stimulates the growth of melanoma cells. Our results show that TSH receptors (TSHR) are expressed by virtually all cutaneous melanocytic lesions, including benign nevi, dysplastic nevi, and melanomas, with higher expression found in malignant and pre-malignant lesions. The finding of TSHR expression by human tumors is confirmed in cultured melanoma cells and melanocytes, in which TSHR expression is demonstrated by immunofluorescent staining, western blotting, and reverse transcriptase-PCR. Melanoma TSHR are functional, as evidenced by the ability of TSH to induce the formation of cAMP and to activate the mitogen-activated protein kinase (MAPK) pathway. Cultured melanoma cells, but not melanocytes, are induced to proliferate at a physiologically relevant concentration of TSH. Taken together, these data support the hypothesis that TSH is a growth factor for human melanoma. Our findings have broad clinical implications for the prevention of melanoma and the management of established disease.

Blotting, Western↗
PubMed1991

Interaction between Pseudomonas aeruginosa and host defenses in cystic fibrosis.

The major causes of morbidity and mortality in cystic fibrosis are chronic pulmonary obstruction and infection. Mucoid Pseudomonas aeruginosa is the primary pathogen in up to 90% of these patients. Once Pseudomonas organisms colonize the airways, they are virtually never eradicated. No defect in systemic host defense has been elucidated, however, several mechanisms contribute to the breakdown in host defenses that allow persistence of this organism in the endobronchial space. These mechanisms involve both bacterial adaptation to an unfavorable host environment and impaired host response. P aeruginosa adapts to the host by expressing excessive mucoid exopolysaccharide and a less virulent form of lipopolysaccharide. These features make it less likely to cause systemic infection, yet still enable it to resist local host defenses. Mucociliary clearance becomes impaired due to abnormal viscoelastic properties of sputum, squamous metaplasia of the respiratory epithelium, and bronchiectasis. Despite a brisk antibody response to a variety of Pseudomonas antigens, several defects in antibody-mediated opsonophagocytosis have been identified. These include (1) development of antibody isotypes that are suboptimal at promoting phagocytosis, (2) formation of immune complexes that inhibit phagocytosis, and (3) proteolytic fragmentation of immunoglobulins in the endobronchial space. Complement-mediated opsonophagocytosis is also compromised by proteolytic cleavage of complement receptors from the cell surface of neutrophils and complement opsonins from the surface of Pseudomonas. The resultant chronic inflammation and infection lead to eventual obliteration of the airways.

Antibodies, Bacterial↗
PubMed1998

Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile.

The expression of Th2-skewed immunity against soluble protein Ags present in the normal environment is recognized as the primary cause of allergic inflammation in atopics. In contrast, nonallergic normal individuals display low level Th1-skewed immunity against the same Ags ("allergens"), which is perceived as conferring protection against Th2-dependent allergic sensitization. The type of T cell memory that develops against these Ags is currently believed to be the result of complex interactions between environmental and genetic susceptibility factors, which occur postnatally when the naive immune system directly confronts the outside environment. The results of the present study challenge this general concept. We demonstrate here for the first time that Th2-skewed responses to common environmental allergens, comprising IL-4, IL-5, IL-6, IL-9, and IL-13, are present in virtually all newborn infants and are dominated by high level production of IL-10. Moreover, these responses are demonstrable within 24 h of culture initiation, arguing against a significant contribution from covert in vitro T cell priming and/or differentiation. These findings imply that the key etiologic factor in atopic disease may not be the initial acquisition of allergen-specific Th2-skewed immunity per se, but instead may be the efficiency of immune deviation mechanisms, which in normal (nonatopic) individuals redirect these fetal immune responses toward the Th1 cytokine phenotype.

Allergens↗
PubMed1998

Platform independent implementation of DICOM-based miniPACS.

Platform independence is an important issue for a software designed to run across a hospital environment which is practically always heterogeneous one. This paper presents a simple miniPACS solution designed over an existing Intranet (Internet limited to a local area network). Platform independence is achieved with Java programming language which allows resulting code to be executed on virtually all machines. System consists of a server application providing DICOM (Digital Imaging and Communications in Medicine) services and clients that can use these services over a TCP/IP connection. The server application is capable of an image storage and supports a query mechanism to allow access to stored data, thus the clients may perform two major functions: providing image data for archiving or image retrieval for viewing. Presented client application provides both these functions. It retrieves stored images for further processing and returns calculated results to the archive. The parts of the system are connected through a DICOM interface. Consequently the system architecture is open and any devices like scanners or viewing stations supporting specific DICOM services may be attached.

Humans↗
PubMed1991

Economic evaluation of drug prescription monitoring systems in the extra-hospital environment.

Drugs expenditure accounts for a significant and rising share of public health expenditure (from 14% in 1980 it has now reached 17% approximately). Many efforts have been made to contain its expansion through tickets (co-payments), formularies, price policies, etc., but overall results have been unsatisfactory. The main cause for this failure may be found in the approach adopted, virtually excluding the evaluation of rational use of drugs. Economic evaluation of drug prescription, comparing cost per DDD, assessing both cost/effectiveness ratios and the monitoring system's efficiency, may contribute to a better control of drug expenditure.

Cost-Benefit Analysis↗
PubMedDate not supplied

Non-ortho PCB levels in various fish species from the east and west coast of Sweden.

Non-ortho (coplanar) PCBs 77, 126 and 169 were determined in a number of fish species from the Swedish coastal environment, using either supercritical fluid extraction (SFE) or the traditional liquid/liquid extraction followed by HPLC separation on porous graphitic carbon (PGC) column prior to GC/MS analysis. While PCB 77 showed the highest concentration level, the TEQ value for PCB 126 was dominant in virtually all the samples analysed. The toxic equivalents, however, indicated some differences in analytical data between 1990 and 1992/93 but these are not significant probably owing to the short period in between.

Animals↗
PubMed2001

Estimating the influence of forests on the overall fate of semivolatile organic compounds using a multimedia fate model.

On the basis of recently reported measurements of semivolatile organic compound (SOC) uptake in forest canopies, simple expressions are derived that allow the inclusion of a canopy compartment into existing non-steady-state multimedia fate models based on the fugacity approach. One such model is used to assess how the inclusion of the canopy compartment in the model affects the calculated overall behavior of SOCs with specific physical--chemical properties. The primary effect of the forest is an increase in the net atmospheric deposition to the terrestrial environment, reducing atmospheric concentrations and accordingly the extent of deposition to the agricultural and aquatic environments. This effect was most pronounced for chemicals with log KOA around 9-10 and log KAW -2 to -3; their average air concentrations during the growing season decreased by a factor of 5 when the canopy compartment was included. Concentration levels in virtually all compartments are decreased at the expense of increased concentrations in the forest soil. The effect of the forest lies not in a large capacity for these chemicals but in the efficiency of pumping the chemicals from the atmosphere to the forest soil, a storage reservoir with high capacity from which the chemicals can return to the atmosphere only with difficulty. Because of seasonal variability of canopy size and atmospheric stability, uptake into forests is higher during spring and summer than in winter. The model suggests that this may dampen temperature-driven seasonal fluctuations of air concentrations and in regions with large deciduous forests may lead to a temporary, yet notable dip in air concentrations during leaf development in spring. A sensitivity analysis revealed a strong effect of forest cover, forest composition, and degradation half-lives. A high degradation loss on the plant surface has the effect of preventing the saturation of the small plant reservoir and can cause very significant reductions in atmospheric concentrations of those SOCs for which uptake in the canopy is limited by the size of the reservoir.

Air Movements↗
PubMed2006

Navigation around London by a taxi driver with bilateral hippocampal lesions.

The time-scale of hippocampal involvement in supporting episodic memory remains a keenly debated topic, with disagreement over whether its role is temporary or permanent. Recently, there has been interest in how navigation by hippocampally-compromised patients in environments learned long ago speaks to this issue. However, identifying patients with damage that is primarily hippocampal, control subjects matched for navigation experience, and testing their in situ navigation, present substantial problems. We met these challenges by using a highly accurate and interactive virtual reality simulation of central London (UK) to assess the navigation ability of a licensed London taxi driver who had sustained bilateral hippocampal damage. In this test, patient TT and matched control taxi drivers drove a virtual London taxi along the streets they had first learned 40 years before. We found that the hippocampus is not required for general orientation in the city either in first person or survey perspectives, detailed topographical knowledge of landmarks and their spatial relationships, or even for active navigation along some routes. However, in his navigation TT was very reliant on main artery or 'A' roads, and became lost when navigation depended instead on non-A roads. We conclude that the hippocampus in humans is necessary for facilitating navigation in places learned long ago, particularly where complex large-scale spaces are concerned, and successful navigation requires access to detailed spatial representations.

Aged↗
PubMed1996

E144S active-site mutant of the Bacillus cereus thermolysin-like neutral protease at 2.8 A resolution.

The X-ray crystal structure of the Bacillus cereus neutral protease (CNP) active-site mutant E144S, in which the putative general base proposed for the thermolysin-like zinc neutral proteases, Glu144, has been replaced by serine, has been determined to a resolution of 2.8 A. This represents the first crystal structure of an active-site mutant of a zinc neutral protease. The E 144S mutant was crystallized in the hexagonal space group, P6(5)22, with unit-cell dimensions a = b = 76.57, c = 201.91 A. Although the ligands involved in zinc coordination in the active site are identical to those found in the wild-type protein, the mutation results in a modified environment around the zinc ion; particularly with respect to the water molecules. While the structure of the mutant is similar to that of wild type, its protease activity is reduced to 0.16% that of the wild-type CNP and the protein is virtually resistant to autolysis in the presence of calcium. The lowered protease activity of the mutant is consistent with the role proposed for Glu144 as the general base in the catalysis of thermolysin-like neutral proteases [Matthews (1988). Acc. Chem. Res. 21, 333-340]. We suggest that the residual activity of the E144S mutant arises from a water molecule, which is found within hydrogen-bonding distance of Ser144, acting as a general base in the catalytic function of the mutant.

Journal Article↗