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PubMed1993

Extracting prototypical facial images from exemplars.

A computer graphic method for extracting a natural image of an individual's facial prototype, or average appearance, from a number of different images of that individual is presented. The process improves upon previous photographic and computational techniques. Synthesis of a person's average expression and pose from a sample of images is derived in an automatic and quantitative way. Possible uses of composite faces produced in this manner in psychological investigations of facial qualities (eg attractiveness) and in applied areas such as telecommunication are pointed out.

Attention↗

PubMed1974

Further analysis of a simple prototypal muscle model near to and far from equilibrium.

The same prototypal model used in a previous paper to illustrate proper construction of a muscle model is modified here with the much more realistic choice e(Deltap) = 10(8) rather than e(Deltap) = 100, where e(Deltap) is the ratio of physiological ATP activity to equilibrium ATP activity. For steady isotonic contractions, the range 1 </= e(Delta) </= 10(4) can be approximated quite well by use of linear terms only in expansions of F (force) and J (ATP flux) in powers of e(Delta) - 1 and v (velocity). This will presumably also be true in most cases of much more complicated models. However, this region is of theoretical interest only (irreversible thermodynamics, etc.) because F and J are very small. In addition, numerical calculations of F and J were made in the region 10(4) </= e(Delta) </= 10(8). The optimal efficiency eta(*) is larger under physiological conditions (about 1%) than at equilibrium by a factor of 2.1 x 10(4). The rate of entropy production is discussed in this connection.

Adenosine Triphosphate↗

PubMed1991

Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates.

Genomic RNA from the human prototype strain H of the hepatitis C virus (HCV-H) has been molecularly cloned and sequenced. The HCV-H sequence reported consists of 9416 nucleotides including the 5' and 3' untranslated regions. HCV-H shows 96% amino acid identity with the American isolate HCV-1 but only 84.9% with the Japanese isolates HCV-J and HCV-BK. In addition to the hypervariable region (region V) previously identified in the putative E2 domain, three other variable domains were identified: region V1 (putative E1), region V2 (putative E2), and region V3 (putative NS5). These regions appear rather conserved (86-100%) among the American isolates (HCV-1 and HC-J1) or among various Japanese isolates (HCV-J, HCV-BK, HCV-JH, and HC-J4) but show striking heterogeneity when the two subgroups are compared (42-87.5% amino acid difference). A structural similarity between the 5'-terminal hairpin structure of HCV and of poliovirus was observed. This study further suggests the existence of at least two genomic subtypes of HCV and confirms a distant relationship between HCV and pestiviruses.

Amino Acid Sequence↗

PubMed1998

Photoactive yellow protein: a structural prototype for the three-dimensional fold of the PAS domain superfamily.

PAS domains are found in diverse proteins throughout all three kingdoms of life, where they apparently function in sensing and signal transduction. Although a wealth of useful sequence and functional information has become recently available, these data have not been integrated into a three-dimensional (3D) framework. The very early evolutionary development and diverse functions of PAS domains have made sequence analysis and modeling of this protein superfamily challenging. Limited sequence similarities between the approximately 50-residue PAS repeats and one region of the bacterial blue-light photosensor photoactive yellow protein (PYP), for which ground-state and light-activated crystallographic structures have been determined to high resolution, originally were identified in sequence searches using consensus sequence probes from PAS-containing proteins. Here, we found that by changing a few residues particular to PYP function, the modified PYP sequence probe also could select PAS protein sequences. By mapping a typical approximately 150-residue PAS domain sequence onto the entire crystallographic structure of PYP, we show that the PAS sequence similarities and differences are consistent with a shared 3D fold (the PAS/PYP module) with obvious potential for a ligand-binding cavity. Thus, PYP appears to prototypically exhibit all the major structural and functional features characteristic of the PAS domain superfamily: the shared PAS/PYP modular domain fold of approximately 125-150 residues, a sensor function often linked to ligand or cofactor (chromophore) binding, and signal transduction capability governed by heterodimeric assembly (to the downstream partner of PYP). This 3D PAS/PYP module provides a structural model to guide experimental testing of hypotheses regarding ligand-binding, dimerization, and signal transduction.

Amino Acid Sequence↗

PubMed1999

Transcriptional coupling between the divergent promoters of a prototypic LysR-type regulatory system, the ilvYC operon of Escherichia coli.

The twin-domain model [Liu, L. F. & Wang, J. C. (1987) Proc. Natl. Acad. Sci. USA 84, 7024-7027] suggests that closely spaced, divergent, superhelically sensitive promoters can affect the transcriptional activity of one another by transcriptionally induced negative DNA supercoiling generated in the divergent promoter region. This gene arrangement is observed for many LysR-type-regulated operons in bacteria. We have examined the effects of divergent transcription in the prototypic LysR-type system, the ilvYC operon of Escherichia coli. Double-reporter constructs with the lacZ gene under transcriptional control of the ilvC promoter and the galK gene under control of the divergent ilvY promoter were used to demonstrate that a down-promoter mutation in the ilvY promoter severely decreases in vivo transcription from the ilvC promoter. However, a down-promoter mutation in the ilvC promoter only slightly affects transcription from the ilvY promoter. In vitro transcription assays with DNA topoisomers showed that transcription from the ilvC promoter increases over the entire range of physiological superhelical densities, whereas transcription initiation from the ilvY promoter exhibits a broad optimum at a midphysiological superhelical density. Evidence that this promoter coupling is DNA supercoiling-dependent is provided by the observation that a novobiocin-induced decrease in global negative superhelicity results in an increase in ilvY promoter activity and a decrease in ilvC promoter activity predicted by the in vitro data. We suggest that this transcriptional coupling is important for coordinating basal level expression of the ilvYC operon with the nutritional and environmental conditions of cell growth.

Bacterial Proteins↗

PubMed2000

Searching for the prototypic eye genetic network: Sine oculis is essential for eye regeneration in planarians.

We have identified a sine oculis gene in the planarian Girardia tigrina (Platyhelminthes; Turbellaria; Tricladida). The planarian sine oculis gene (Gtso) encodes a protein with a sine oculis (Six) domain and a homeodomain that shares significant sequence similarity with so proteins assigned to the Six-2 gene family. Gtso is expressed as a single transcript in both regenerating and fully developed eyes. Whole-mount in situ hybridization studies show exclusive expression in photoreceptor cells. Loss of function of Gtso by RNA interference during planarian regeneration inhibits eye regeneration completely. Gtso is also essential for maintenance of the differentiated state of photoreceptor cells. These results, combined with the previously demonstrated expression of Pax-6 in planarian eyes, suggest that the same basic gene regulatory circuit required for eye development in Drosophila and mouse is used in the prototypic eye spots of platyhelminthes and, therefore, is truly conserved during evolution.

Amino Acid Sequence↗

PubMed2001

A complex signaling module governs the activity of MalT, the prototype of an emerging transactivator family.

MalT, the specific activator of the maltose regulon, is the prototype of a family of high-molecular-mass ATP-binding bacterial transcription activators. On binding of its two positive effectors, the inducer maltotriose and ATP, MalT oligomerizes to an active state competent for promoter binding and transcription activation. In addition to its previously known DNA-binding domain, limited proteolysis showed that MalT contains three other domains, the boundaries of which were accurately delimited by N-terminal microsequencing. The N-terminal domain alone binds ATP. Maltotriose binding involves an extended region corresponding to domains 2 and 3, although weak binding to domain 3 alone was also observed. Moreover, maltotriose binding induces a conformational shift involving a movement of both domains 1 and 3 with respect to domain 2, leading to the active form of the protein. Sequence examination of the MalT homologues suggests that these three domains might constitute a signaling module.

Adenosine Diphosphate↗

PubMed2001

The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors.

Serine proteases are involved in many processes in the nervous system and specific inhibitors tightly control their proteolytic activity. Thrombin is thought to play a role in tissue development and homeostasis. To date, protease nexin-1 is the only known endogenous protease inhibitor that specifically interferes with thrombotic activity and is expressed in the brain. In this study, we report the detection of a novel thrombin inhibitory activity in the brain of protease nexin-1(-/-) mice. Purification and subsequent analysis by tandem mass spectrometry identified this protein as the phosphatidylethanolamine-binding protein (PEBP). We demonstrate that PEBP exerts inhibitory activity against several serine proteases including thrombin, neuropsin, and chymotrypsin, whereas trypsin, tissue type plasminogen activator, and elastase are not affected. Since PEBP does not share significant homology with other serine protease inhibitors, our results define it as the prototype of a novel class of serine protease inhibitors. PEBP immunoreactivity is found on the surface of Rat-1 fibroblast cells and although its sequence contains no secretion signal, PEBP-H(6) can be purified from the conditioned medium upon recombinant expression.

Amino Acid Sequence↗

PubMed2002

p105.Ikappa Bgamma and prototypical Ikappa Bs use a similar mechanism to bind but a different mechanism to regulate the subcellular localization of NF-kappa B.

p105, also known as NF-kappaB1, is an atypical IkappaB molecule with a multi-domain organization distinct from other prototypical IkappaBs, like IkappaBalpha and IkappaBbeta. To understand the mechanism by which p105 binds and inhibits NF-kappaB, we have used both p105 and its C-terminal inhibitory segment known as IkappaBgamma for our study. We show here that one IkappaBgamma molecule binds to NF-kappaB dimers wherein at least one NF-kappaB subunit is p50. We suggest that the obligatory p50 subunit in IkappaBgamma.NF-kappaB complexes is equivalent to the N-terminal p50 segment in all p105.NF-kappaB complexes. The nuclear localization signal (NLS) of the obligatory p50 subunit is masked by IkappaBgamma, whereas the NLS of the nonobligatory NF-kappaB subunit is exposed. Thus, the global binding mode of all IkappaB.NF-kappaB complexes seems to be similar where one obligatory (or specific) NF-kappaB subunit makes intimate contact with IkappaB and the nonobligatory (or nonspecific) subunit is bound primarily through its ability to dimerize. In the case of IkappaBalpha and IkappaBbeta, the specific NF-kappaB subunit in the complex is p65. In contrast to IkappaBalpha.NF-kappaB complexes, where the exposed NLS of the nonspecific subunit imports the complex to the nucleus, p105.NF-kappaB and IkappaBgamma.NF-kappaB complexes are cytoplasmic. We show that the death domain of p105 (also of IkappaBgamma) is essential for the cytoplasmic sequestration of NF-kappaB by p105 and IkappaBgamma. However, the death domain does not mask the exposed NLS of the complex. We also demonstrate that the death domain alone is not sufficient for cytoplasmic retention and instead functions only in conjunction with other parts in the three-dimensional scaffold formed by the association of the ankyrin repeat domain (ARD) and NF-kappaB dimer. We speculate that additional cytoplasmic protein(s) may sequester the entire p105.NF-kappaB complex by binding through the death domain and other segments, including the exposed NLS.

Animals↗

PubMed2002

Evaluation of a prototype multi-posture office chair.

Office chairs have often been designed to promote a single 'correct' rather rigid and upright posture, yet it is acknowledged that allowing changes in posture is good ergonomics practice. The present study investigated office worker's preferences for a standard shaped typist's chair (ST) and a prototype multi-posture (PMP) office chair designed to allow its users a variety of sitting positions. Forty-two (22 male and 20 female) telesales personnel (12), clerical staff (12) and researchers (18) used ST or PMP in their workplace for the first week of a 2-week study (with an even number in each work area). The PMP chair was introduced to participants with a brief lecture on how to use it and with an information booklet. Following this, each participant completed a chair comfort questionnaire. In the second week, participants swapped chairs and again completed the chair comfort questionnaire. At the end of the second week participants were also asked to complete a separate questionnaire about the usability of the information booklet that accompanied the PMP chair. Statistically significant differences in subject's rating of the two chairs were observed in 7 out of 19 questions. On a 100 mm scale, the ST chair was rated as having a greater mean overall acceptability, desirability and suitability for body build than the PMP chair. Participants also claimed to achieve better posture in the ST chair, that they tipped forward less and were more satisfied with its width. Although the participants generally preferred the ST chair, the PMP chair received more favourable ratings among the researchers who were quite mobile in their work, and in whom there was a trend for less neck, shoulder and upper back discomfort. More participants reported an overall preference for the PMP chair. The findings suggest that a more aesthetically acceptable PMP chair should be developed, peoples' reasons for preferring a more traditionally designed chair should be explored, and that the effect of postural stability education on personal preconceptions should be examined to obtain an optimal combination of healthy sitting habits, comfort and aesthetic qualities in an office chair.

Adult↗

PubMedDate not supplied

Skeletal myopathy in transgenic mice carrying human prototype c-Ha-ras gene.

Skeletal myopathy was found in almost all-transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mouse). Microscopically, variation of the muscle fiber size, centrally placed nuclei, regenerating fibers, and interstitial fibrosis were evident; hyalinization and necrosis were sometimes observed in the skeletal muscle (femoralis and pectoralis) of the rasH2 mice. Inflammatory changes in the skeletal muscle or abnormality of adjacent peripheral nerve were not observed. The features were essentially similar to those of muscular dystrophy. Although the severity was relatively mild compared to 34-week-old rasH2 mice, the skeletal myopathy was also observed in younger male (10 weeks of age) rasH2 mice. In nontransgenic littermates, skeletal myopathy was not observed. The mRNA of human c-Ha-ras product was detected in femoral muscle from the rasH2 mice by RT-PCR. In conclusion, these data suggest that skeletal myopathy is occurring in almost all rasH2 mice. Integration of c-Ha-ras gene is thought to be crucial to pathogenesis of skeletal myopathy in the rasH2 mice. Further characterization of the muscular lesion and its pathogenesis are needed to explore the possibility of rasH2 mouse becoming a new model for muscular dystrophy.

Animals↗

PubMedDate not supplied

Mutation and overexpression of the transgene in ethylnitrosourea-induced tumors in mice carrying a human prototype c-Ha-ras gene.

To investigate mechanisms underlying accelerated carcinogenesis in mice carrying a human prototype c-Ha-ras gene (rasH2 mouse), mutations and the expression profile of the transgene were evaluated in 14 tumors induced by a single injection of ethylnitrosourea (ENU), with or without additional beta-estradiol 3-benzoate (EB) treatment. Although no codon 12 mutations were detected, changes in codon 61 were evident in all lung adenocarcinomas, skin squamous cell carcinomas and forestomach squamous cell carcinomas examined. The mRNA levels of the transgene in these lesions were also elevated 1.71- to 4.77-fold, 3.04- to 5.18-fold, and 3.00- to 5.67-fold, respectively, in comparison with those in the normal livers of rasH2 mice. The results obtained in this study suggest that mutations in codon 61 and amplification of the transgene play key roles in the carcinogenesis induced by ENU in rasH2 mice.

Adenocarcinoma↗

PubMedDate not supplied

PROTOTYPES: an urban model program of treatment and recovery services for dually diagnosed perinatal program participants.

PROTOTYPES, a women's treatment program located in Los Angeles, is described in terms of its services for pregnant and parenting women with coexisting substance abuse and mental health disorders. The philosophy of treatment, goals and objectives, treatment planning process, and treatment content are discussed. Management of the milieu, relational model considerations and staff self-care issues are presented in addition to future directions in treatment and research on women with coexisting disorders.

Diagnosis, Dual (Psychiatry)↗

PubMedDate not supplied

A review of rapid prototyping (RP) techniques in the medical and biomedical sector.

The evolution of rapid prototyping (RP) technology is briefly discussed, and the application of RP technologies to the medical sector is reviewed. Although the use of RP technology has been slow arriving in the medical arena, the potential of the technique is seen to be widespread. Various uses of the technology within surgical planning, prosthesis development and bioengineering are discussed. Some possible drawbacks are noted in some applications, owing to the poor resolution of CT slice data in comparison with that available on RP machines, but overall, the methods are seen to be beneficial in all areas, with one early report suggesting large improvements in measurement and diagnostic accuracy as a result of using RP models.

Biomedical Engineering↗

PubMedDate not supplied

Medical rapid prototyping and 3D CT in the manufacture of custom made cranial titanium plates.

This report describes a new method of custom making cranial titanium plates for the repair of skull defects. We have combined 3D CT imaging and surface modelling with rapid prototyping (RP) technology to produce physical models of our patients' skulls from which custom titanium plates were made. We have expanded the use of image processing tools applied to the CT image data to fabricate a representation of the skull defect. Medical RP models are relatively expensive and particular attention has been paid to developing image processing methods to reduce costs. Our technique used the patient as their own model and generated data from the contralateral side of the head where appropriate. We present the results of 10 patients who have had a custom made cranial titanium plate fitted and discuss the models for these cases. The benefits of our custom made titanium plates are reduced patient attendances to hospital and a more accurate titanium plate which has improved fitting and cosmesis.

Bone Plates↗

PubMed1991

The binding of prototype lexitropsins to the minor groove of DNA: quantum chemical studies.

Ab initio calculations (Hartree-Fock) using the 6-31 G basis set have been performed on two prototype lexitropsins or information-reading molecules. The latter are DNA minor groove binding agents related to the A.T recognizing netropsin in which each of the two N-methylpyrrole moieties is replaced in turn by 1-methylimidazole and which thereby confers the property of recognizing G.C sites.Ab initio treatment was possible by examining composities of separate non-conjugated segments of the molecules. Geometry optimized conformations, energies and distribution of electrostatic charges within the molecules were derived. The ab initio derived parameters of the geometry optimized conformations of these lexitropsins were used to interpret their interaction with different sequences within the minor groove of B-DNA.

Base Sequence↗

PubMed2001

Incineration of paper sludge in a prototype vortexing fluidized bed combustor.

All experiments were carried out in a prototype vortexing fluidized bed combustor (VFBC). The dimension of the combustion chamber is 0.7 x 1.4 x 2 m, and the freeboard section is 1 m i.d. and 4 m in height. Paper sludge was used as the feeding material. Two types of coal particles were employed as the supplementary fuel. In order to understand the characteristics of the VFBC system for paper sludge incineration, the effect of various operating parameters, such as the primary airflow, excess air ratio, and secondary airflow rates, on temperature distribution, ash elutriation, combustion efficiency, and pollutant emissions were investigated.

Air Pollution↗

PubMed2003

Mini-fingerprints for virtual screening: design principles and generation of novel prototypes based on information theory.

Binary fingerprint representations of molecular structure and properties are convenient computational tools for similarity searching in compound databases and virtual screening (VS). We are investigating the design of relatively simple fingerprints for the identification of molecules having similar biological activity and recognition of remote similarity relationships. Since our designs are considerably shorter than other fingerprints used in VS, we have previously termed them "mini-fingerprints" (MFPs). A key aspect of the design strategy is the identification of suitable molecular descriptors. Whereas our initial fingerprint designs have relied on descriptor combinations that performed well in compound classification according to biological activity, second generation MFPs encode combinations of descriptors with high information content in large compound databases and high frequency of occurrence in drug-like molecules. Thus, the design of these new fingerprints does not depend on the analysis of specific classes of bioactive compounds, but rather on descriptor information content in large compound databases. Systematic evaluation of fingerprint performance in VS test calculations demonstrates that these new prototypes perform better than previously generated MFPs. The analysis described herein provides an example for the development of search tools for VS.

Environmental Pollutants↗