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Biomedical subjects

R F Wang

Publications and source records attributed to R F Wang.

At least 19 recordsLinked to original sources

Development of a membrane-array method for the detection of human intestinal bacteria in fecal samples.

A membrane-array method was developed for the detection of human intestinal bacteria in fecal samples without using the expensive microarray-arrayer and laser-scanner. The 16S rDNA sequences of 20 predominant human intestinal bacterial species were used to design oligonucleotide probes. Three 40-mer oligonucleotides specific for each bacterial species (total 60 probes) were synthesized and applied to nitrocellulose membranes. Digoxigenin (DIG)-labeled 16S rDNAs were amplified by polymerase chain reaction (PCR) from human fecal samples or pure cultured bacteria using two universal primers, and were hybridized to the membrane-array. Hybridization signals were read by NBT/BCIP color development. The 20 intestinal bacterial species tested were Bacteroides thetaiotaomicron, B. vulgatus, B. fragilis, B. distasonis, Clostridium clostridiiforme, C. leptum, Fusobacterium prausnitzii, Peptostreptococcus productus, Ruminococcus obeum, R. bromii, R. callidus, R. albus, Bifidobacterium longum, B. adolescentis, B. infantis, Eubacterium biforme, E. aerofaciens, Lactobacillus acidophilus,Escherichia coli, and Enterococcus faecium. The two universal primers were able to amplify full size 16S rDNA from all of the 20 bacterial species tested. The hybridization results indicated that the membrane-array method is a reliable technique for the detection of predominant human intestinal bacteria in the fecal samples. The result was also confirmed by using specific PCR methods for these bacteria.

Adult↗

Immunization against endogenous retroviral tumor-associated antigens.

Endogenous retroviral gene products have been found in some human tumors, and therefore, may serve as antigens for immunotherapy approaches. The murine colorectal carcinoma CT26 and melanoma B16 have recently been found to express the endogenous retroviral gene products gp70 and p15E, respectively, that can serve as antigens recognized by T cells. To date, though, there has been no demonstration of tumor treatment using an endogenous retroviral protein. In this study, we demonstrate that mice immunized with recombinant vaccinia encoding the gp70 H2-L(d)-restricted minimal determinant were protected from CT26 tumor challenge. Splenocytes from mice immunized with vaccinia gp70 specifically secreted IFN-gamma in response to gp70 peptide-pulsed stimulators. Although this strategy could protect against subsequent tumor challenge, it was ineffective against established tumors. Therefore, to investigate the treatment of established CT26 or B16 lung metastases, mice were treated with cultured dendritic cells (DCs) pulsed with gp70 or p15E peptide. Significant inhibition of established lung metastases required immunization with peptide-pulsed DCs pretreated with CD40 ligand that has been demonstrated to increase the T-cell stimulatory activity of DCs. The ability to immunize against endogenous retroviral tumor antigens may have relevance in the induction of antitumor immunity for some human cancers.

Animals↗

CD4(+) T cell recognition of MHC class II-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: association with NY-ESO-1 antibody production.

NY-ESO-1 is a tumor-specific shared antigen with distinctive immunogenicity. Both CD8(+) T cells and class-switched Ab responses have been detected from patients with cancer. In this study, a CD4(+) T cell line was generated from peripheral blood mononuclear cells of a melanoma patient and was shown to recognize NY-ESO-1 peptides presented by HLA-DP4, a dominant MHC class II allele expressed in 43--70% of Caucasians. The ESO p157--170 peptide containing the core region of DP4-restricted T cell epitope was present in a number of tumor cell lines tested and found to be recognized by both CD4(+) T cells as well as HLA-A2-restricted CD8(+) T cells. Thus, the ESO p157--170 epitope represents a potential candidate for cancer vaccines aimed at generating both CD4(+) and CD8(+) T cell responses. More importantly, 16 of 17 melanoma patients who developed Ab against NY-ESO-1 were found to be HLA-DP4-positive. CD4(+) T cells specific for the NY-ESO-1 epitopes were generated from 5 of 6 melanoma patients with NY-ESO-1 Ab. In contrast, no specific DP4-restricted T cells were generated from two patients without detectable NY-ESO-1 Ab. These results suggested that NY-ESO-1-specific DP4-restricted CD4(+) T cells were closely associated with NY-ESO-1 Ab observed in melanoma patients and might play an important role in providing help for activating B cells for NY-ESO-1-specific Ab production.

Alleles↗

The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor immunity.

The identification of tumor antigens has generated a resurgence of interest in immunotherapy for cancer. However, both clinical and animal studies suggest that therapeutic strategies that have mainly focused on the use of CD8+ T cells (and MHC class I-restricted tumor antigens) are not effective in eliminating cancer cells. Recent interest has been directed towards the use of CD4+ T cells in generating antitumor immunity. To this end, the identification of MHC class II-restricted tumor antigens that can stimulate CD4+ T cells might provide opportunities for developing effective cancer vaccines.

Animals↗

Validation of finite element analysis in dental ceramics research.

STATEMENT OF PROBLEM: In vitro dental materials strength testing of ceramic restorations primarily has involved mechanical evaluations of simplified models. The finite element method (FEM) provides a mathematic analysis to predict strength values, but neither methodology is without the potential for errors. PURPOSE: The purpose of this study was to demonstrate the advantages of combining mechanical testing results and FEM data to determine the strengths of a layered ceramic beam when the layered materials and positions are varied. MATERIAL AND METHODS: Eight finite element 5 x 20 x 1-mm layered beams were modeled. Four of the modeled beams were of the same layered arrangements as physical specimens from a previously published study. The remaining 4 modeled beams provided intermediate layered arrangements not evaluated in the earlier study. A force in newtons was applied in the center of the top layer of each beam until fracture. finite element analysis was performed, and the data were compared with mechanical strength test results from the earlier study. RESULTS: The FEM data of the 8 models demonstrated a linear decrease in load-bearing capacity as the layer thickness of the core material decreased and the layer thickness of the veneer material increased. The progressively decreasing values for the FEM beams were 170, 144, 140, 134, 72, 43, 34, and 27 N. The mean load-bearing capacities of 3 of the 4 mechanically tested beams compared favorably with the FEM data. The strength of the fourth mechanically tested beam, a veneer/core layered arrangement, was 110 N, which was lower than the corresponding FEM value (140 N). The 110 N value fell outside the decreasing linear progression for load, indicating that the FEM data were more accurate and reliable than the mechanical data. CONCLUSION: No one perfect method exists for testing the strength of dental materials. The best approach is to use the results from both mechanical testing and finite element analysis, which together may provide more reliable and valid data than either method alone.

Aluminum Oxide↗

Effect of pilocarpine 4% in combination with latanoprost 0.005% or 8-iso prostaglandin E2 0.1% on intraocular pressure in laser-induced glaucomatous monkey eyes.

PURPOSE: To compare the effect of pilocarpine, an agent that reduces uveoscleral outflow, on the ocular hypotensive efficacy of latanoprost and 8-iso prostaglandin E2 (PGE2). METHODS: Each of the two treatment groups was composed of the same eight monkeys with unilateral laser-induced glaucoma. Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:00 AM on the baseline day (Thursday before treatment week) and on treatment days 1, 3, and 5 (Monday, Wednesday, and Friday). On all five treatment days, one drop of pilocarpine 4% was administered at 9:00 AM and 3:00 PM and one drop of latanoprost 0.005% or 25 microL of 8-iso PGE2 0.1% was administered at 10:00 AM and 4:00 PM. RESULTS: One hour after pilocarpine instillation on day 1, the reduction of IOP was similar (P > 0.90) in both treatment groups, 7.6 +/- 1.1 mm Hg (mean +/- standard error of the mean ) in the latanoprost group and 7.4 +/- 0.8 mm Hg in the 8-iso PGE2 group. However, the IOP effects of the two treatment groups became significantly different (P < 0.05) beginning 2 hours after dosing with latanoprost or 8-iso PGE, on day 1. A difference (P < 0.05) between the two groups persisted at all subsequent measurements. The reduction of IOP lessened with repeated dosing in the latanoprost and 8-iso PGE2 groups. Three hours after dosing with pilocarpine and two hours after dosing with the prostanoids, the IOP reduction was 8.3 +/- 0.9 mm Hg in the latanoprost group and 9.9 +/- 0.6 mm Hg in the 8-iso PGE2 group on day 1, and 2.1 +/- 1.0 mm Hg in the latanoprost group and 7.3 +/- 0.9 mm Hg in the 8-iso PGE1 group on day 5. CONCLUSIONS: The smaller reductions in IOP with pilocarpine and latanoprost than with pilocarpine and 8-iso PGE2 show that pilocarpine blocks much more of the ocular hypotensive effect of latanoprost than of 8-iso PGE2. The results also indicate that pilocarpine and latanoprost are mutually antagonistic. Enhancement of uveoscleral outflow appears to account for most of the ocular hypotensive effect of latanoprost and for much less of the ocular hypotensive effect of 8-iso prostaglandin E2.

Administration, Topical↗

Visual search has memory.

By monitoring subjects' eye movements during a visual search task, we examined the possibility that the mechanism responsible for guiding attention during visual search has no memory for which locations have already been examined. Subjects did reexamine some items during their search, but the pattern of revisitations did notfit the predictions of the memory less search model. In addition, a large proportion of the refixations were directed at the target, suggesting that the revisitations were due to subjects' remembering which items had not been adequately identified. We also examined the patterns of fixations and compared them with the predictions of a memoryless search model Subjects' fixation patterns showed an increasing hazard function, whereas the memoryless model predicts a flat function. Lastly, we found no evidence suggesting that fixations were guided by amnesic covert scans that scouted the environment for new items during fixations. Results do not support the claims of the memorvless search model, and instead suggest that visual search does have memory.

Adult↗

Molecular cloning, nucleotide sequence, and expression of genes encoding a polycyclic aromatic ring dioxygenase from Mycobacterium sp. strain PYR-1.

Mycobacterium sp. strain PYR-1 degrades high-molecular-weight polycyclic hydrocarbons (PAHs) primarily through the introduction of both atoms of molecular oxygen by a dioxygenase. To clone the dioxygenase genes involved in PAH degradation, two-dimensional (2D) gel electrophoresis of PAH-induced proteins from cultures of Mycobacterium sp. strain PYR-1 was used to detect proteins that increased after phenanthrene, dibenzothiophene, and pyrene exposure. Comparison of proteins from induced and uninduced cultures on 2D gels indicated that at least six major proteins were expressed (105, 81, 52, 50, 43, and 13 kDa). The N-terminal sequence of the 50-kDa protein was similar to those of other dioxygenases. A digoxigenin-labeled oligonucleotide probe designed from this protein sequence was used to screen dioxygenase-positive clones from a genomic library of Mycobacterium sp. strain PYR-1. Three clones, each containing a 5,288-bp DNA insert with three genes of the dioxygenase system, were obtained. The genes in the DNA insert, from the 5' to the 3' direction, were a dehydrogenase, the dioxygenase small (beta)-subunit, and the dioxygenase large (alpha)-subunit genes, arranged in a sequence different from those of genes encoding other bacterial dioxygenase systems. Phylogenetic analysis showed that the large alpha subunit did not cluster with most of the known alpha-subunit sequences but rather with three newly described alpha subunits of dioxygenases from Rhodococcus spp. and Nocardioides spp. The genes from Mycobacterium sp. strain PYR-1 were subcloned and overexpressed in Escherichia coli with the pBAD/ThioFusion system. The functionality of the genes for PAH degradation was confirmed in a phagemid clone containing all three genes, as well as in plasmid subclones containing the two genes encoding the dioxygenase subunits.

Cloning, Molecular↗

Validation of a polymerase chain reaction method for the detection of rendered bovine-derived materials in feedstuffs.

This study validated a polymerase chain reaction-based method for the detection of a specific bovine mitochondrial gene derived from rendered bovine tissues and admixed with complete animal feed. Four laboratories participated in this effort: one state laboratory and three Food and Drug Administration (FDA) laboratories, including one FDA field laboratory. The protocol used a statistical approach of 90% probability, with a 95% confidence interval for determining acceptable rates of false-positive and false-negative samples. Each participating laboratory analyzed 30 samples of feed each containing 0, 0.125, and 2.0% bovine meat and bone meal (BMBM), for a total of 90 feed samples. The samples were randomized such that the analysts were unaware of the true identity of the test samples. The results demonstrated that all laboratories met the acceptance criteria established for this protocol. The overall rates of false-negative results were 0.83% (1/120) at the level of 0.125% BMBM and 1.67% (2/120) at the level of 2% BMBM. The overall rate of false-negative results for all levels of BMBM was 1.25% (3/240). The rate for false-positive results was 0.83%.

Animal Feed↗

Updating egocentric representations in human navigation.

Seven experiments tested whether human navigation depends on enduring representations, or on momentary egocentric representations that are updated as one moves. Human subjects pointed to unseen targets, either while remaining oriented or after they had been disoriented by self-rotation. Disorientation reduced not only the absolute accuracy of pointing to all objects ('heading error') but also the relative accuracy of pointing to different objects ('configuration error'). A single light providing a directional cue reduced both heading and configuration errors if it was present throughout the experiment. If the light was present during learning and test but absent during the disorientation procedure, however, subjects showed low heading errors (indicating that they reoriented by the light) but high configuration errors (indicating that they failed to retrieve an accurate cognitive map of their surroundings). These findings provide evidence that object locations are represented egocentrically. Nevertheless, disorientation had little effect on the coherence of pointing to different room corners, suggesting both (a) that the disorientation effect on representations of object locations is not due to the experimental paradigm and (b) that room geometry is captured by an enduring representation. These findings cast doubt on the view that accurate navigation depends primarily on an enduring, observer-free cognitive map, for humans construct such a representation of extended surfaces but not of objects. Like insects, humans represent the egocentric distances and directions of objects and continuously update these representations as they move. The principal evolutionary advance in animal navigation may concern the number of unseen targets whose egocentric directions and distances can be represented and updated simultaneously, rather than a qualitative shift in navigation toward reliance on an allocentric map.

Adult↗

Identification of CD4+ T cell epitopes from NY-ESO-1 presented by HLA-DR molecules.

In previous studies, the shared cancer-testis Ag, NY-ESO-1, was demonstrated to be recognized by both Abs and CD8+ T cells. Gene expression of NY-ESO-1 was detected in many tumor types, including melanoma, breast, and lung cancers, but was not found in normal tissues, with the exception of testis. In this study, we describe the identification of MHC class II-restricted T cell epitopes from NY-ESO-1. Candidate CD4+ T cell peptides were first identified using HLA-DR4 transgenic mice immunized with the NY-ESO-1 protein. NY-ESO-1-specific CD4+ T cells were then generated from PBMC of a patient with melanoma stimulated with the candidate peptides in vitro. These CD4+ T cells recognized NY-ESO-1 peptides or protein pulsed on HLA-DR4+ EBV B cells, and also recognized tumor cells expressing HLA-DR4 and NY-ESO-1. A 10-mer peptide (VLLKEFTVSG) was recognized by CD4+ T cells. These studies provide new opportunities for developing more effective vaccine strategies by using tumor-specific CD4+ T cells. This approach may be applicable to the identification of CD4+ T cell epitopes from many known tumor Ags recognized by CD8+ T cells.

Amino Acid Sequence↗

Cloning, sequencing, and expression in Escherichia coli of a cytochrome P450 gene from Cunninghamella elegans.

A polyclonal antibody against microsomes of a fungus, Cunninghamella elegans, was used to screen a C. elegans cDNA library. A cDNA clone, containing an open reading frame (ORF) encoding a protein of 389 amino acids (aa), was obtained. GenBank comparison (BLAST) showed that the protein was closely related to P450 because a heme-binding region, which is highly conserved in all P450 sequences, was found in the ORF protein. Using an oligo probe designed from this C. elegans heme-binding region to rescreen the cDNA library, we obtained three new clones. Sequence comparison showed that the three clones, with different length cDNA inserts, were from the same mRNA of the C. elegans P450 gene. One clone had the full C. elegans P450 gene, encoding 473 aa with a molecular mass of 54958.60, whereas the 389 was a part of the 473 aa without the N-terminal. The entire C. elegans P450 gene was successfully subcloned and overexpressed in a plasmid-Escherichia coli system (pQE30). Immunostaining with three antibodies (CYP1A1, CYP2E1, and CYP3A1) against mammalian P450 enzymes and benzidine staining for hemoproteins showed positive results for the recombinant protein expressed in E. coli. A phylogenetic tree was constructed by comparison of other fungal P450s to the C. elegans sequence. The C. elegans P450 clustered close to the cyp51 family and was named cyp509A1 by the International Committee on the Nomenclature for Cytochrome P450 Enzymes.

Amino Acid Sequence↗

Effect of latanoprost or 8-iso prostaglandin E2 alone and in combination on intraocular pressure in glaucomatous monkey eyes.

OBJECTIVE: To evaluate the possible additivity of the effects of latanoprost and 8-iso prostaglandin E2 (8-iso PGE2) on intraocular pressure (IOP) in monkey eyes with laser-induced glaucoma. METHODS: The IOP was measured hourly for 6 hours beginning at 9:30 AM on day 1 (baseline day), days 6 and 7 (single-agent therapy), and days 13 and 14 (combination therapy with both agents). Following 1 day of baseline measurement, 4 monkeys with unilateral glaucoma received monotherapy) twice daily with either 1 drop of 0.005% latanoprost, or 0.1% 8-iso PGE2, 25 microL, at 9:30 AM and 3:30 PM from days 2 through 7. From days 8 through 14, both agents were applied twice daily 5 minutes apart. RESULTS: The maximum reduction of IOP (mean +/- SEM) was 8.8 +/- 1.9 mmHg (26%) (P<.05) with latanoprost alone and 6.5 +/- 1.0 mmHg (21%) (P<.0l) with 8-iso PGE2 alone, 2 hours after the morning dosing on day 7. A further reduction of IOP of 4.0 +/- 0.6 mm Hg was produced when 8-iso PGE2 was added to latanoprost and of 3.0 +/- 0.7 mm Hg was produced when latanoprost was added to 8-iso PGE2 on day 13 before the morning dosing. Combination therapy with both agents caused maximum IOP reductions from baseline of 11.3 +/- 3.0 mm Hg (33%) (P<.05) (latanoprost with 8-iso PGE2 added) and of 9.8 +/- 1.3 mm Hg (31%) (P<.01) (8-iso PGE2 with latanoprost added) on day 14. CONCLUSION: Latanoprost and 8-iso PGE2 have an additive effect on IOP in glaucomatous monkey eyes. CLINICAL RELEVANCE: At least 50% of patients are treated with more than 1 ocular hypotensive medication. Thus, the determination of the additive effects on IOP of glaucoma medications will help to define optimum treatment regimens.

Animals↗

A rapid method for PCR detection of bovine materials in animal feedstuffs.

Rapid identification of bovine materials in animal feedstuffs is essential for effective control of a potential source of bovine spongiform encephalopathy. We have developed a rapid method for the detection of the presence of bovine materials in animal feeds. Animal feed samples were prepared by a Chelex-100 treatment method, then subjected to polymerase chain reaction (PCR) detection. The assay can be completed in 2 h including 30 min for sample preparation, 35-65 min for PCR cycling and 30 min for gel electrophoresis. This method is not only rapid, simple and consistent, but also avoids a hazardous waste disposal issue associated with a previously described guanidine thiocyanate (GuSCN) extraction-PCR method.

Animal Feed↗

Recognition of shared melanoma antigens in association with major HLA-A alleles by tumor infiltrating T lymphocytes from 123 patients with melanoma.

A total of 123 tumor-infiltrating T lymphocyte (TIL) cultures established from patients with HLA-A1, -A2, -A3, -A24, or -A31 metastatic melanoma in the Surgery Branch, National Cancer Institute, were screened for recognition of shared melanoma antigens including five melanosomal proteins (tyrosinase, MART-1/melan-A, gp100, TRP1, TRP2) as well as peptides derived from MAGE-1 and MAGE-3. Examination of the specificity of these T cells indicated that 16% of HLA-A1 TIL, 57% of HLA-A2 TIL, 7% of HLA-A3 TIL, 13% of HLA-A24 TIL, and 27% of HLA-A31 TIL recognized shared melanoma antigens restricted by major histocompatibility complex class I. Melanosomal proteins were frequently recognized by these TIL, and MART-1(27-35), gp100(154-162), gp100(209-217), and gp100(280-288) represent highly immunogenic epitopes that were recognized by a high percentage of HLA-A2 restricted melanoma reactive TIL. Recognition of gp100 by HLA-A2 restricted TIL significantly correlated with clinical response to adoptive immunotherapy with TIL in 21 HLA-A2 melanoma patients (p = 0.024). Four HLA-A1, two HLA-A2, two HLA-A3, one HLA-A24, and two HLA-A31 restricted shared antigen-specific TIL did not recognize the previously identified antigens tested in this study, and may be useful for the identification of new melanoma antigens. The observation that TILs isolated from patients with metastatic melanoma recognized melanosomal proteins in the context of predominant HLA-A alleles implies that it may be possible to develop immunotherapies for patients with melanoma expressing diverse HLA types.

Alleles↗

Comparison of the ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears added to timolol in glaucomatous monkey eyes.

PURPOSE: To investigate the additive ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears to timolol in monkey eyes with laser-induced unilateral glaucoma. METHODS: Eight monkeys were used and each animal received all four combinations of drugs in a randomized fashion during the study. The washout period between each combination was at least 2 weeks. Intraocular pressure (IOP) was measured at 8:30 AM, 11:00 AM, 1:00 PM, and 3:30 PM on day 1 (untreated baseline), day 2 (timolol treatment alone), and days 3 through 5 (combination therapy with two drugs). One drop of 0.5% timolol was topically applied at 3:45 PM on day 1 and at 8:45 AM and 3:45 PM on days 2 through 5. One drop of 0.2% brimonidine or 2% dorzolamide or artificial tears was added on day 2 at 4:00 PM and at 9:00 AM and 4:00 PM on days 3 through 5, or latanoprost was added at 9:00 AM on days 3 through 5. RESULTS: Compared with timolol alone, the maximal additive reduction in IOP which occurred on day 5 was 4.8 +/- 0.8 mm Hg (mean +/- standard error of the mean) with timolol plus brimonidine, 5.6 +/- 1.0 mm Hg with timolol plus dorzolamide, 4.3 +/- 1.0 mm Hg with timolol plus latanoprost, and 2.0 +/- 0.5 mm Hg with timolol plus artificial tears (P < 0.01). At all measurements, timolol plus brimonidine, timolol plus dorzolamide, and timolol plus latanoprost caused greater (P < 0.05) IOP reductions than did timolol plus artificial tears. The additive IOP-lowering effect was similar (P > 0.60) when comparing timolol plus brimonidine and timolol plus dorzolamide, timolol plus brimonidine and timolol plus latanoprost, timolol plus dorzolamide and timolol plus latanoprost at all measurements, but timolol plus dorzolamide caused a greater (P < 0.05) reduction of IOP than did timolol plus latanoprost at 0 hours on day 5. CONCLUSIONS: The addition of brimonidine, dorzolamide, or latanoprost to timolol caused similar additional reductions of IOP in glaucomatous monkey eyes.

Animals↗

Cloning, expression, and characterization of the katG gene, encoding catalase-peroxidase, from the polycyclic aromatic hydrocarbon-degrading bacterium Mycobacterium sp. strain PYR-1.

A 81-kDa protein from Mycobacterium sp. strain PYR-1 was expressed in response to exposure of the strain to the polycyclic aromatic hydrocarbon pyrene and recovered by two-dimensional gel electrophoresis. The N-terminal sequence of the protein indicated that it was similar to catalase-peroxidase. An oligonucleotide probe designed from this sequence was used to screen a genomic library of Mycobacterium sp. strain PYR-1, and a positive clone, containing a part of the gene encoding the 81-kDa protein, was isolated. A gene-walking technique was used to sequence the entire gene, which was identified as katG for catalase-peroxidase. The deduced KatG protein sequence showed significant homology to KatGII of Mycobacterium fortuitum and clustered with catalase-peroxidase proteins from other Mycobacterium species in a phylogenetic tree. The katG gene was expressed in Escherichia coli to produce a protein with catalase-peroxidase activity. Since the induction of this catalase-peroxidase occurred in pyrene-induced cultures and the exposure of these cultures to hydrogen peroxide reduced pyrene metabolism, our data suggest that this enzyme plays a role in polycyclic aromatic hydrocarbon metabolism by strain PYR-1.

Bacterial Proteins↗

Heading judgments in minimal environments: the value of a heuristic when invariants are rare.

Observers made systematic heading judgments in two experiments simulating their translation through an environment with only two trees. When those trees converged or decelerated apart, observers tended to follow the invariant information and make heading judgments outside the near member of the pair. When those trees accelerated apart, however, observers tended to follow the heuristic information and make judgments outside the far member, although this result was tempered by the angular separation between the trees and their relative acceleration. The simultaneous existence and use of invariants and heuristics are discussed in terms of different metatheoretical approaches to perception.

Environment↗