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PubMed1999

Evolutionary versus prototype analyses of the concept of disorder.

The harmful dysfunction (HD) analysis of the concept of disorder (J. C. Wakefield, 1992a) holds that disorders are harmful failures of internal mechanisms to perform their naturally selected functions. S. O. Lilienfeld and L. Marino (1995) proposed instead that disorder is a Roschian prototype concept without defining properties. Against the HD analysis, they argued that many disorders are not failures of naturally selected functions because they are either designed reactions (e.g., fever) or failures of functions that are not naturally selected (e.g., reading disorder). The HD analysis is defended here against these and other objections and compared with the Roschian account. It is argued that the objections are based on conceptual confusions and can be turned around to provide strong new support for the HD analysis. A series of conceptual experiments demonstrates the superior explanatory power of the HD analysis and disconfirms the Roschian account.

Biological Evolution↗
PubMed1986

Learning and memory for personality prototypes.

Although personality traits are commonly assumed to be represented in memory as schemata, little research has addressed whether such schemata can be learned from observation. Subjects in three studies classified 60 person instances into group members and nonmembers as defined by the instances' match to a complex personality prototype. To simulate learning of fuzzy categories, each person instance provided conflicting cues to group membership. Learning for instances' group membership was excellent across studies. In Study 1, frequency of cues indicating group membership was greatly overestimated among nongroup instances. In Study 2, schema-consistent memory bias was revealed for person instances. In Study 3, schemata of consistently positive (or negative) traits were learned faster than arbitrary schemata. The findings implicated frequency sensitivity of memory (Estes, 1986), and a model of probabilistic cued-memory retrieval was developed to account for the effects. The findings were then discussed in relation to everyday cognitive performance.

Adult↗
PubMed1996

Influence of prototypes on perceptions of prejudice.

Two studies examined the influence of cultural stereotypes and personal factors (one's race, gender) on perceptions of racial and gender discrimination. Overall, the data suggest that our perceptions of prejudice are strongly influenced by specific expectations regarding who are the prototypic perpetrators and victims of prejudice. More general expectations regarding out-group conflict or regarding only the characteristics of the perpetrator appear to have less of an impact on such perceptions. Additionally, women were found to be more likely than men to perceive sexism directed against men and racism directed at African Americans and Caucasians. Also, African Americans were more likely than Caucasians to perceive racist events against Whites and Blacks. The implications of these data are discussed.

Adult↗
PubMed1991

An experimental evaluation of a prototype public access nutrition information system for supermarkets.

Located the Nutrition for a Lifetime System (NLS-1), a prototype interactive information system, in a large supermarket to help users decrease high-fat food purchases and increase high-fiber food purchases. Study participants were randomly assigned to control (n = 23; used the NLS-1 to enter food purchases only) or experimental (n = 26; viewed videodisc instructional programs, received prompts, made commitments, received feedback from the NLS-1) conditions. According to data entered in the NLS-1 and actual food shopping receipts, experimental participants significantly reduced higher fat purchases. Increases in higher fiber purchases favored the experimental group but were not significant.

Adult↗
PubMed1989

An on-line investigation of prototype and exemplar strategies in classification.

Although prototype- and exemplar-based models of categorization are very different in character, they have proved difficult to distinguish experimentally. The research described here presents a priming technique for assessing the type of information retrieved at the moment that a categorization decision is made. This technique avoids many of the problems inherent in the standard paradigms. Data from six experiments are presented that demonstrate the usefulness of the technique and also address basic questions about the categorization process. Results bolster previous suggestions that categorization strategies may be mixed within a single experimental task and highlight the need for more specific predictions about when each strategy will come into play.

Adult↗
PubMed2000

Rapid prototyping of patterned functional nanostructures

Living systems exhibit form and function on multiple length scales and at multiple locations. In order to mimic such natural structures, it is necessary to develop efficient strategies for assembling hierarchical materials. Conventional photolithography, although ubiquitous in the fabrication of microelectronics and microelectromechanical systems, is impractical for defining feature sizes below 0.1 micrometres and poorly suited to pattern chemical functionality. Recently, so-called 'soft' lithographic approaches have been combined with surfactant and particulate templating procedures to create materials with multiple levels of structural order. But the materials thus formed have been limited primarily to oxides with no specific functionality, and the associated processing times have ranged from hours to days. Here, using a self-assembling 'ink' we combine silica-surfactant self-assembly with three rapid printing procedures--pen lithography, ink-jet printing, and dip-coating of patterned self-assembled monolayers--to form functional, hierarchically organized structures in seconds. The rapid-prototyping procedures we describe are simple, employ readily available equipment, and provide a link between computer-aided design and self-assembled nanostructures. We expect that the ability to form arbitrary functional designs on arbitrary surfaces will be of practical importance for directly writing sensor arrays and fluidic or photonic systems.

Journal Article↗
PubMed2001

A prototype storage ring for neutral molecules.

The ability to cool and manipulate atoms with light has yielded atom interferometry, precision spectroscopy, Bose-Einstein condensates and atom lasers. The extension of controlled manipulation to molecules is expected to be similarly rewarding, but molecules are not as amenable to manipulation by light owing to a far more complex energy-level spectrum. However, time-varying electric and magnetic fields have been successfully used to control the position and velocity of ions, suggesting that these schemes can also be used to manipulate neutral particles having an electric or magnetic dipole moment. Although the forces exerted on neutral species are many orders of magnitude smaller than those exerted on ions, beams of neutral dipolar molecules have been successfully slowed down in a series of pulsed electric fields and subsequently loaded into an electrostatic trap. Here we extend the scheme to include a prototype electrostatic storage ring made of a hexapole torus with a circumference of 80 cm. After injection, decelerated bunches of deuterated ammonia molecules, each containing about 106 molecules in a single quantum state and with a translational temperature of 10 mK, travel up to six times around the ring. Stochastic cooling might provide a means to increase the phase-space density of the stored molecules in the storage ring, and we expect this to open up new opportunities for molecular spectroscopy and studies of cold molecular collisions.

Journal Article↗
PubMed1994

Drug excretion mediated by a new prototype of polyspecific transporter.

Cationic drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liver. In the proximal tubules, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are different from the previously identified neuronal monoamine transporters and ATP-dependent multidrug exporting proteins. Here we report the isolation of a complementary DNA from rat kidney that encodes a 556-amino-acid membrane protein, OCT1, which has the functional characteristics of organic cation uptake over the basolateral membrane of renal proximal tubules and of organic cation uptake into hepatocytes. OCT1 is not homologous to any other known protein and is found in kidney, liver and intestine. As OCT1 translocates hydrophobic and hydrophilic organic cations of different structures, it is considered to be a new prototype of polyspecific transporters that are important for drug elimination.

Amino Acid Sequence↗
PubMed2000

Structural analysis of WW domains and design of a WW prototype.

Two new NMR structures of WW domains, the mouse formin binding protein and a putative 84.5 kDa protein from Saccharomyces cerevisiae, show that this domain, only 35 amino acids in length, defines the smallest monomeric triple-stranded antiparallel beta-sheet protein domain that is stable in the absence of disulfide bonds, tightly bound ions or ligands. The structural roles of conserved residues have been studied using site-directed mutagenesis of both wild type domains. Crucial interactions responsible for the stability of the WW structure have been identified. Based on a network of highly conserved long range interactions across the beta-sheet structure that supports the WW fold and on a systematic analysis of conserved residues in the WW family, we have designed a folded prototype WW sequence.

Amino Acid Sequence↗
PubMed2001

Recombinant maxi-K channels on transistor, a prototype of iono-electronic interfacing.

We report on the direct electrical interfacing of a recombinant ion channel to a field-effect transistor on a silicon chip. The ion current through activated maxi-K(Ca) channels in human embryonic kidney (HEK293) cells gives rise to an extracellular voltage between cell and chip that controls the electronic source-drain current. A comparison with patch-clamp recording shows that the channels at the cell/chip interface are fully functional and that they are significantly accumulated there. The direct coupling of potassium channels to a semiconductor on the level of an individual cell is the prototype for an iono-electronic interface of ligand-gated or G protein-coupled ion channels and the development of screening biosensors with many transfected cells on a chip with a large array of transistors.

Cell Line↗
PubMed1998

The many faces of Src: multiple functions of a prototypical tyrosine kinase.

c-src was first isolated as the normal cellular homologue of v-src, the transforming gene of Rous Sarcoma virus (Stehelin et al., 1976). As the first proto-oncogene described and one of the first molecules demonstrated to have tyrosine kinase activity, Src has provided a prototype for understanding signal transduction involving tyrosine phosphorylation. Comparison between c-src and activated or transforming mutants of Src including v-src, combined with recent data on the structure of Src family kinases has provided new insight into their regulation. In this review, I will discuss the function of the various domains of Src in light of these mutational and structural studies.

Animals↗
PubMed2001

Comparison of three-dimensional computed tomography with rapid prototype models in the management of coronoid hyperplasia.

OBJECTIVES: To compare (1) the accuracy of 3DCT with rapid prototyping (RP) models and (2) their application in the management of coronoid hyperplasia. METHODS: An adult dry skull was used to compare 3DCT and a RP model for accuracy of reproduction; Polymerisation contraction and 17 distances between 27 anatomical points were measured. Two patients with coronoid process hyperplasia were assessed by means of 3DCT and plastic models. RESULTS: Differences in measurements with the RP model and the dried skull were smaller than those with 3DCT (P=0.04). Polymerisation contraction was greater than the errors in reproduction with the RP model and approximately equal to those with the 3DCT. The coronoid process was thick and prominent in the patients with coronoid process hyperplasia and the small space and early contact between zygomatic arch and the coronoid process demonstrated. The plastic model duplicated the exostosis of the inner surface of the malar bone facing the concavity of the elongated process. The coronoid process had an anterior tilt in one case. CONCLUSION: The plastic model duplicated the relationship between the maxillofacial deformity and the coronoid process with tolerable accuracy. Trismus may be due to the direction as well as the length of the enlarged coronoid process.

Adolescent↗
PubMed2005

Synthesis, crystal structure and magnetic properties of o-carboranyl nitronyl nitroxide biradical: a prototype of a three-dimensional analogue of o-benzoquinodimethane.

We have designed and synthesised a new carborane derivative containing two nitronyl nitroxides. This molecule can be considered as a prototype of a three-dimensional analogue of o-benzoquinodimethane. The magnetic susceptibility of a crystalline sample revealed that this biradical possesses a weak antiferromagnetic interaction (theta = -1.05(4) K) and an ESR study in frozen matrix in the 5.4-104 K range gave an intramolecular antiferromagnetic interaction of -27(2) K. The synthesis, physical properties and DFT calculation result are also reported.

Journal Article↗
PubMed2005

The prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway.

HVS (herpesvirus saimiri) is the prototype gamma-2 herpesvirus. This is a subfamily of herpesviruses gaining importance since the identification of the first human gamma-2 herpesvirus, Kaposi's sarcoma-associated herpesvirus. The HVS ORF 57 (open reading frame 57) protein is a multifunctional transregulatory protein homologous with genes identified in all classes of herpesviruses. Recent work has demonstrated that ORF 57 has the ability to bind viral RNA, shuttles between the nucleus and cytoplasm and promotes the nuclear export of viral transcripts. In the present study, we show that ORF 57 shuttles between the nucleus and cytoplasm in a CRM-1 (chromosomal region maintenance 1)-independent manner. ORF 57 interacts with the mRNA export factor REF (RNA export factor) and two other components of the exon junction complex, Y14 and Magoh. The association of ORF 57 with REF stimulates recruitment of the cellular mRNA export factor TAP (Tip-associated protein), and HVS infection triggers the relocalization of REF and TAP from the nuclear speckles to several large clumps within the cell. Using a dominant-negative form of TAP and RNA interference to deplete TAP, we show that it is essential for bulk mRNA export in mammalian cells and is required for ORF 57-mediated viral RNA export. Furthermore, we show that the disruption of TAP reduces viral replication. These results indicate that HVS utilizes ORF 57 to recruit components of the exon junction complex and subsequently TAP to promote viral RNA export through the cellular mRNA export pathway.

Active Transport, Cell Nucleus↗
PubMed1995

Two different isoschizomers of the type-II restriction endonuclease Taq I (T/CGA) within the same Thermus isolate: Tsp32 I, an enzyme with similar heat stability properties to the prototype enzyme Taq I, and Tsp32 II, a hyperthermostable isoschizomer of Taq I.

We have recently screened 112 separate isolates of the genus Thermus, collected from neutral and alkaline hot water springs on four continents, for the presence of the Type-II restriction endonuclease Taq I (T/CGA). One particular isolate from the Azores (strain 32) was found to contain high levels of a restriction endonuclease with the same recognition and cleavage site as Taq I. Initial studies revealed that the partially purified enzyme from strain 32 was considerably more resistant to heat inactivation than the prototype enzyme Taq I, being able to withstand temperatures at least 10 degrees C higher than Taq I, before showing evidence of heat inactivation. Subsequently it became clear that the partially purified extract from strain 32 contains two separate enzymes, both of which are isoschizomers of Taq I. One of the enzymes, Tsp32 I, has similar thermal stability characteristics to Taq I, whereas the second Taq I isoschizomer, Tsp32 II, found in the same Thermus isolate as Tsp32 I, is considerably more thermostable than Taq I, retaining full enzyme activity up to a temperature of 85 degrees C. Tsp32 I and Tsp32 II were further distinguished by virtue of their different requirements for magnesium ions.

Base Sequence↗
PubMed2002

Evaluation in an anaesthetic simulator of a prototype of a new drug administration system designed to reduce error.

Ten anaesthetists were observed while providing anaesthesia for two simulated surgical procedures, twice using conventional methods and twice using a prototype of a new drug administration system designed to reduce error. Aspects of each method were rated by users on 10-cm visual analogue scales (10 being best) and comments were invited. Median safety scores were 7.7 cm (range 4.3-8.9) for the new system and 4.6 cm (1.3-8.2) for conventional methods (p = 0.009). The new system was compared favourably with conventional methods in respect of safety (p = 0.005), clinical acceptability (p = 0.008), organisation and layout (p = 0.047), and acceptability for use on patients (p = 0.005). The new system saved time in the preparation of drugs both before anaesthesia (105 vs. 346 s; p < 0.001) and during anaesthesia (20 vs. 104 s; p < 0.001). Comments facilitated development of the system and the evaluation endorsed proceeding to a clinical trial.

Anesthesiology↗
PubMed2003

Monocytes and neutrophils from tuberculosis patients are insensitive to anti-inflammatory effects triggered by the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP).

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis where formyl peptides, which are cleavage products of bacterial and mitochondrial proteins, are present. In this study, we demonstrated that interferon gamma (IFN)-gamma and interleukin (IL)-10 induced the overexpression of the receptor for the Fc portion of IgG I (FcgammaRI) in monocytes from tuberculosis (TB) patients, showing that these cells respond to IFN-gamma and IL-10 signals. We also demonstrated that lower doses of IL-10 render monocytes from TB patients less responsive to higher doses of the cytokine. Although the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is a well-known proinflammatory agonist, we have demonstrated previously that preincubation of monocytes with FMLP inhibited the up-regulation of FcgammaRI induced by IFN-gamma or IL-10. This effect was not observed in monocytes from TB patients. FMLP also induced the down-regulation of the expression of FcgammaRI in monocytes that had been activated already with IFN-gamma. However, this effect of FMLP was not observed in monocytes from TB patients and supernatants from monocytes obtained from these patients were incapable of inducing the down-regulation of FcgammaRI. In contrast to normal donors, supernatants from FMLP-treated neutrophils from TB patients did not modify the basal level of expression of FcgammaRI in monocytes from normal donors. In conclusion, in this study we demonstrated the existence of two novel mechanisms that may contribute to the pathological effects generated by M. tuberculosis: the enhancement of FcgammaRI in response to IFN-gamma and IL-10, and the unresponsiveness to the anti-inflammatory effects induced by formyl peptides.

Cells, Cultured↗