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Abstraction of prototypical information by adults and 10-month-old infants.

The primary purpose of this study was to investigate whether preverbal infants, when presented with exemplars of an artificially constructed category, would abstract a prototypical representation of the category, and if so, whether this representation was formed by either "counting" or "averaging" the features that were varying among category members. Two experiments are reported. In Experiment 1, a set of stimuli was developed and tested for which it was demonstrated that adult subjects would readily abstruct either a modal or an average prototypical representation. The type of representation abstracted was found to be dependent on the discriminability of the feature values. In Experiment 2, 10-mo.-old infants were tested using a habituation paradigm with the stimuli developed in the first experiment. The results of this study indicated that the infants were also able to abstract the featural information that was varying among the exemplars of the category, and the infants formed an internal represenatation of the category by averaging feature values. Thus, the results clearly imply that infants are able to constructively process visual information and hence take a more active role in category formation than had been previously believed.

Adult

Prototyping a genetics deductive database.

We are developing a laboratory notebook system known as the Genetics Deductive Database. Currently our prototype provides storage for biological facts and rules with flexible access via an interactive graphical display. We have introduced a formal basis for the representation and reasoning necessary to order genome map data and handle the uncertainty inherent in biological data. We aim to support laboratory activities by introducing an experiment planner into our prototype. The Genetics Deductive Database is built using new database technology which provides an object-oriented conceptual model, a declarative rule language, and a procedural update language. This combination of features allows the implementation of consistency maintenance, automated reasoning, and data verification.

Animals

Oncogenic activation of human R-ras by point mutations analogous to those of prototype H-ras oncogenes.

R-ras, K-rev-1/rap and TC21, are more closely related to prototype H-ras than any other known members of the ras superfamily. We recently isolated a mutationally activated TC21 oncogene from a human ovarian carcinoma cell line. Based upon these observations, we sought to re-examine the transforming potential of R-ras, which was reported earlier to lack transforming capacity. Mutations were introduced into the R-ras gene at codons 38 or 87, analogous to positions 12 and 61, respectively, responsible for H-ras oncogene activation. While both mutations resulted in acquisition of R-ras transforming capacity for NIH3T3 cells the position 61 was shown to be more active. Transfectants expressing either R-ras mutant formed colonies in soft agar and were tumorigenic in vivo. As has been reported for H-ras, R-ras cooperated with c-raf-1 in inducing transformation of NIH3T3 cells. These results imply interactions in R-ras and c-raf-1 signaling pathways. We observed R-ras transcripts of 4.6 and 1.2 kb ubiquitously expressed in each of a variety of tissues examined. All these findings raise the possibility that R-ras, like prototype ras genes, may be mutationally activated as an oncogene in some human malignancies.

3T3 Cells

Oxygen performance of a prototype nonconventional hydrogel.

UNLABELLED: INTRODUCTION. Oxygen permeability (Dk) of available hydrogel materials used for soft contact lenses is currently restricted by the oxygen permeability of water at 80 Dk units. A predicted upper limit for conventional hydrogels amenable for use as a contact lens, has been 37 Dk units obtained with a water content of 80%. Methods for increasing oxygen permeability beyond that determined by water content must be explored, in order to further advance the physiological compatibility of hydrogel contact lenses. METHODS: Oxygen transport characteristics of a prototype nonconventional hydrogel contact lens material were derived in terms of human equivalent oxygen percentage (EOP) and thickness (L). The oxygen permeability of the material and oxygen transmissibilities (Dk/L) of various thicknesses were computed on the bases of a recently published nonlinear EOP vs. Dk/L relationship. RESULT: The material's oxygen permeability (Dk) was determined to be approximately 35 Dk units compared to 12.7 Dk units calculated for a conventional gel material having the same water content (52% H2O). Oxygen permeability equivalent to that obtained with high-water conventional gels was achieved using this mid-water nonconventional hydrogel. The prototype material was apparently also capable of low critical thicknesses typical of low-water conventional gels. DISCUSSION: Should new gel materials be durable with critical thicknesses in the "ultra-thin" range, nonconventional gel lenses could be capable of super and perhaps even hyper transmissibility with central minus lens EOP between 15-18.5% and Dk/L between 50-90 Dk/L units. The conventional relationships between water content and oxygen transmissibility of hydrogel contact lenses appear to have been surpassed. However, significant additional hurdles have yet to be overcome before nonconventional hydrogel materials can be ready for the ophthalmic marketplace.

Biocompatible Materials

The informatics superhighway: prototyping on the World Wide Web.

We have experimented with developing a prototype Surgeon's Workstation which makes use of the World Wide Web client-server architecture. Although originally intended merely as a means for obtaining user feedback for use in designing a "real" system, the application has been adopted for use by our Department of Surgery. As they begin to use the application, they have suggested changes and we have responded. This paper illustrates some of the advantages we have found for prototyping with Web-based applications, including security aspects.

Computer Communication Networks

Examination of tooth-drying techniques: evaluation in-vitro of a prototype warm-air tooth dryer.

A prototype, rechargeable, warm-air tooth dryer is evaluated and its capabilities compared with those of an established mains electricity powered dryer (Handi-Dri). The evaluation includes warm-up cycle, maximum temperature and constancy of temperature of air output, battery discharge profile, time required to dry etched enamel, ability to dry wet filter paper, flow rate and pressure of air output, convenience and ease of use. Selected tests were also applied to a dental 3-in-1 syringe. Alternative methods of drying the tooth surface are also reviewed. The prototype was found to be suitable for tooth drying; it was considered safer and more convenient than the Handi-Dri and offered advantages over other methods.

Air Pressure

Retrovirus from human T-cell leukemia virus type I-associated myelopathy is the same strain as a prototype human T-cell leukemia virus type I.

A retrovirus was isolated from a T-cell line that was established from lymphocytes in the cerebrospinal fluid of a patient with human T-cell leukemia virus type I-associated myelopathy (HAM), and its genome was sequenced. The nucleotide sequence of the 3' half of the total genome was identical in 99.5% of the nucleotides to that of the prototype human T-cell leukemia virus type I that was derived from a patient with adult T-cell leukemia. These results indicate that the same retrovirus human T-cell leukemia virus type I is associated with both a neurological disease, HAM, and a lymphoproliferative disease, adult T-cell leukemia.

Amino Acid Sequence

Assessing the competency of patients with Alzheimer's disease under different legal standards. A prototype instrument.

OBJECTIVE: To assess empirically the competency of patients with Alzheimer's disease (AD) to consent to medical treatment under different legal standards (LSs). DESIGN: Comparison of normal older subjects and patients with AD on measures of competency to consent to medical treatment. SETTING: University medical center. SUBJECTS: Normal older control subjects (n = 15) and patients with probable AD (n = 29 [15 with mild and 14 with moderate AD]). MAIN OUTCOME MEASURES: Two specialized clinical vignettes were developed that test a subject's capacity to consent to medical treatment under five well-established LSs for this competency: LS1, evidencing treatment choice; LS2, making the reasonable choice; LS3, appreciating consequences of choice; LS4, providing rational reasons for choice; and LS5, understanding treatment situation and choices. Performance on the LSs was compared across control and AD groups using Student's t test, chi 2, and analysis of variance. Demented subjects were categorized as competent, marginally competent, or incompetent under each LS by using a cutoff score derived from normal control performance. RESULTS: No differences between groups emerged for LS1 and LS2. Control subjects performed significantly better than patients with mild AD on LS4 and LS5, and significantly better than patients with moderate AD on LS3, LS4, and LS5. Patients with mild AD performed significantly better than patients with moderate AD on LS4 and LS5. With respect to competency status, patients with AD showed a consistent and progressive pattern of compromise (marginal competence or incompetence) related to dementia severity and stringency of the LS. CONCLUSIONS: A reliable prototype instrument validly discriminated the competency performance and classified the competency status of control subjects and patients with mild and moderate AD under five LSs for competency to consent to medical treatment. While the groups performed equivalently on minimal standards requiring merely a treatment choice (LS1) or the reasonable treatment choice (LS2), patients with mild AD had difficulty with more difficult standards requiring rational reasons (LS4) and understanding treatment information (LS5), and patients with moderate AD had difficulty with appreciation of consequences (LS3), rational reasons (LS4), and understanding treatment (LS5). The results raised the concern that many patients with mild AD may not be competent to consent to treatment and supported the value of standardized clinical vignettes for assessment of competency in dementia.

Aged

Responses given by A and B quasi-therapists to differing sexual roles in an intropunitive-neurotic prototype: an analogue study.

Twenty-four male undergraduate students were selected on the basis of their A--B status. Six Ss of each type were assigned randomly to one of two videotaped stimulus conditions, an adequate or an inadequate sexual role variant of an intropunitive neurotic prototype. Two dependent measures, response time and number of confrontations, were used and conceptualized in terms of an approach-avoidance continuum. Differential responding on the basis of the Ss' A--B status was not supported in this study.

Adolescent

Human rheumatoid factor cross-idiotypes. III. Bla monoclonal rheumatoid factor, prototype of the BLA cross-idiotype group, has distinct kappa chains related to the V kappa III subgroup and VH4 heavy chains.

The BLA cross-idiotype (XId) is present on a unique subset of rheumatoid factors (RF) that cross-react with DNA-histone. In this study, prototype Bla monoclonal RF was shown from serologic investigations and N-terminal amino acid sequence analysis to have distinct kappa chains related to the V kappa III subgroup and VH4 heavy chains. The amino terminus of the heavy chain was cyclized, rendering the protein resistant to Edman degradation and providing a possible investigator bias to the published Ig sequence data to date. This appears to be the first definitive report of a serum IgM that expresses the VH4 gene. RF with DNA cross-reactivity have been reported to be produced by human and mouse cloned cells that have the VH4 or homologous mouse Vh36-60 gene.

Amino Acid Sequence

Stability studies of the components of a prototype penicillinase (beta-lactamase)-linked ELISA kit.

Penicillinase (beta-lactamase) enzyme-linked immunosorbent assay (ELISA) for various reproductive hormones developed in the laboratory were found to have wide applicability in the fertility check clinic of the Institute. A need was thought to transform these assays into ready-to-use kit forms. Therefore, prototype ELISA kits for these hormones were developed and stability of the individual component was ascertained at various temperatures (room temperature, 37 degrees C and 2-8 degrees C). Stability studies were conducted on previously validated assay for pregnanediol-3 alpha-glucuronide (PdG). The studies showed that immunosorbents (antibody coated plates) are stable at room temperature for a period of 2 weeks, at 37 degrees C for 1 week and at 2-8 degrees C for a period of 9 months when preserved after treatment with glycerol solution. The lyophilised conjugate, standard and immunoassay buffer, colour reagent, and its substrate were stable at 37 degrees C up to 1 week and at room temperature up to 2 weeks and at 2-8 degrees C for a period of 6 months, during which the stability was studied.

Enzyme Stability

Circulating interferon in the guinea pig infected with the XJ, prototype Junin virus strain.

The interferon (IFN) induction capacity of the XJ prototype strain of Junín virus (JV) was investigated in the guinea pig model. Circulating alpha IFN was detected in 50% of the animals from days 2 to 9 postinfection (pi) and in 100% at day 11 pi, when all animals were in the premortem stage. Individual levels ranged from 20 to 1,280 guinea pig IFN units (GPIFNU)/ml. A correlation between XJ strain virulence and IFN titers was recorded. A possible role of IFN as a pathogenic factor in the outcome of the disease is discussed.

Animals

Analysis of G418-selected Rat2 cells containing prototype, variant, mutant, and chimeric JC virus and SV40 genomes.

The human polyomavirus JC virus (JCV) is highly tumorigenic in rodents, but transforms cells in culture inefficiently. To explore the basis for JCV's restricted transforming behavior, nonpermissive Rat2 cells were contransfected with pSV2-neo (encodes G418 resistance) and viral DNAs including prototype, variant, and mutant JCV genomes and two JCV-SV40 chimeras. By selecting cells displaying G418 resistance, lines were established that contain viral DNA and exhibit a wide range of transformed phenotypes. The G418-resistant lines were tested for their ability to grow under anchorage-independent conditions, to overgrow a monolayer of untransformed cells, and to form dense colonies on plastic. Expression of the viral T and t proteins and interaction of T protein with the cellular anti-oncoprotein p53 were measured. Also determined was the number of intact viral early coding regions integrated within the cellular DNA. The results of these studies suggested that most of the G418-resistant lines failed to express JCV T protein above a minimum threshold level required for their conversion to a fully transformed phenotype. In anchorage-independent growth assays, higher levels of a 17-kDa T-related peptide in JCV transformants appeared to compensate for decreased T antigen levels. Comparison of the T to p53 ratios in the cell lysates suggested that the quaternary structure of the JCV protein differed from that of its SV40 counterpart in the T-p53 complex. The presence of multiple vs single integrated copies of the viral genome in the cells did not correlate with elevated T antigen expression or an enhanced transformation status.

Animals

A prototype device for linear accelerator-based extracranial radiosurgery.

A prototype frame for accurate stereotactic localization and linear accelerator (LINAC)-based treatment of extracranial targets was developed. The ECRSF is designed to employ either spinal or skeletal osseous fixation to immobilize the area of interest and then encircle the targeted region with a traditional orthogonal, three-axis system. A series of experiments (n = 5) with semi-radiolucent calibration targets (n = 15) and computed tomography (CT) scanning using the EC showed that a mean localization error of 0.98 +/- 0.22 mm was obtainable in the last two and most accurate series of experiments with these targets (n = 8). Using the LINAC to irradiate these same targets demonstrated an overall radiation treatment accuracy ranging from 1.4 to 2.0 mm. This discrepancy between localization error and overall radiation treatment error can be explained by a lack of isocentricity of the LINAC treatment which is typically less than 1 mm and can be as low as 0.5 mm. These data demonstrate that extracranial stereotactic radiosurgery is now technically feasible and that the accuracy of such treatment would be acceptable for clinical treatment.

Equipment Design

Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients.

Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.

Absorption

Serologically atypical adenovirus strains of subgenus D are different in their genome from the respective prototypes.

Seven adenovirus strains of subgenus D, related to adenovirus types 8, 10, 13, 19, 23, 24 and 26, but atypical in their serological reactions or in hemagglutinin properties, were characterized by neutralization and hemagglutination-inhibition. DNA restriction analysis with five endonucleases showed that each of the strains was strikingly different from the respective prototype.

Adenoviruses, Human

A neural model for nonassociative learning in a prototypical sensory-motor scheme: the landing reaction in flies.

Nonassociative learning is an important property of neural organization in both vertebrate and invertebrate species. In this paper we propose a neural model for nonassociative learning in a well studied prototypical sensory-motor scheme: the landing reaction of flies. The general structure of the model consists of sensory processing stages, a sensory-motor gate network, and motor control circuits. The paper concentrates on the sensory-motor gate network which has an agonist-antagonist structure. Sensory inputs to this circuit are transduced by chemical messenger systems whose dynamics include depletion and replenishment terms. The resulting circuit is a gated dipole anatomy and we show that it gives a good account of nonassociative learning in the landing reaction of the fly.

Animals

Pharmacokinetics and metabolism of the mixed-function hypoxic cell sensitizer prototype RSU 1069 in mice.

RSU 1069 is a leading compound in the class of mixed-function hypoxic cell sensitizers. Possessing an alkylating aziridine function as well as a nitro group, it represents an important prototype molecule for new sensitizer development. Using a novel HPLC assay for RSU 1069 and its metabolites with a cyanopropyl column, we studied the detailed pharmacokinetics and metabolism of this drug in mice. An i.v. dose of 100 mg kg-1 produced peak plasma concentrations of about 100 micrograms ml-1. Absorption was rapid after i.p. injection but peak plasma concentrations were some three- to fourfold lower, giving an i.p. bioavailability of 55%. The elimination t1/2 was route-dependent; e.g. after 50 mg kg-1 the t1/2 was 37.2 and 22.4 min for the i.v. and i.p. routes respectively (P less than 0.001). There was also an indication of dose-dependent kinetics, with a 37% increase in elimination t1/2 when the i.p. dose was doubled from 50 to 100 mg kg-1. Oral bioavailability was low. The volume of distribution was 0.65-1.31 ml g-1 at 50 mg kg-1, but tissue penetration was limited. Brain/plasma ratios ranged from 9.3% to 66.8%, while the mean steady-state tumour/plasma ratio was 28.4%, a value considerably less than the 80%-100% ratios occurring with the neutral 2-nitroimidazole misonidazole. About 18% and 8% of a dose were excreted as the parent drug and the ring-opened hydrolysis product (RSU 1137) in the 8 h urine, indicating the likelihood of extensive metabolism via aziridine-ring removal and nitroreduction. RSU 1137 was also detected in mouse plasma and tissues and, in contrast to the aziridine ring-intact parent compound, gave tumour/plasma ratios of 100%. These studies should provide a pharmacokinetic basis for the evaluation and development of improved mixed-function sensitizers.

Animals