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PubMed1981

Original domain for the serum albumin family arose from repeated sequences.

The characteristic three-domain structure has been conserved throughout mammalian evolution by serum albumin and its fetal counterpart, alpha-fetoprotein. Thus, one still detects 35.2% amino acid sequence homology between bovine serum albumin and murine alpha-fetoprotein. Yet, natural selection cannot be invoked as the major factor responsible for the observed conservation of these sequences, for the simple reason of their dispensability. Inherited analbuminemia is apparently a harmless trait in man and the rat. The conservation appears inherent in their repetitious origin. Each protein is made of triplicate copies of the ancestral domain. Furthermore, analysis of the published sequence data suggests that the original coding sequence for the ancestral domain arose as repeats of the 18-base-long primordial building block sequence TTC-ACA-GAG-GAG-CAG-CTG specifying Phe-Thr-Glu-Glu-Gln-Leu and its shorter subsidiary TTC-ATG-GAG-GAG specifying Phe-Met-Glu-Glu. Consequently, the homology between bovine serum albumin and alpha-fetoprotein is mostly confined to small segments still specified by recognizable descendants of these building block sequences. The point to be made here is that evolutionary conservation of coding sequences can be an inherent property; natural selection need not be invoked.

Amino Acid Sequence↗
PubMed1977

Increase in level of functional messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP) during induction by cyclic adenosine 3':5'-monophosphate.

The administration of N6, O2'-dibutyryl cyclic AMP and theophylline to fasted-refed rats produces an 8-fold stimulation of the relative rate of hepatic phosphoenolpyruvate carboxykinase synthesis in 90 min, as measured by isotopic immunochemical techniques in vivo. The mechanism of this induction was studied first by using a homologous, noninitiating cell-free protein-synthesizing system derived from the liver of fasted-refed, cyclic AMP-treated rats. In such a system, a 5-fold increase in phosphoenolpyruvate carboxykinase synthseis is observed at 20 min post-treatment and a 9-fold stimulation at 75 min, indicating a rapid increase in the number of ribosomes engaged in the translation of the enzyme mRNA after exposure to cyclic AMP. The level of functional mRNA coding for phosphoenolpyruvate carboxykinase was then assayed in a wheat germ protein-synthesizing system capable of using rat liver mRNA as template. The template activity for phosphoenolpyruvate carboxykinase synthesis is greatly increased in the poly(A)-containing RNA isolated from cyclic AMP-induced animals. Both the increase in the capacity of the liver extract for in vitro phosphoenolpyruvate carboxykinase synthesis and the emergence of enzyme mRNA detected in the wheat germ assay are completely prevented by a pretreatment with cordycepin at doses which inhibit the appearance in the cytoplasm of newly synthesized poly(A)-containing RNA. These data demonstrate that the induction of hepatic phosphoenolpyruvate carboxykinase by cyclic AMP is characterized by the rapid build-up of newly synthesized, actively translated mRNA coding for the enzyme. The messenger accumulation could be due to an increase in the rate of its production or a decrease in the rate of its degradation.

Animals↗
PubMed1983

Homology between coding and noncoding sequences within the human class I HLA antigen gene.

In our previous paper, we identified 32 recurring base oligomers (1 decamer, 4 octamers, 9 heptamers and 18 hexamers) within the coding sequence for the mouse class I major histocompatibility (MHC) antigen H-2Kb. The compilation of these recurring base oligomers led to the conclusion that the entire ancestral coding sequence for class 1 MHC antigens evolved from tandem repeats of the one 45 base-long primordial building block base sequence. As with most other mammalian genes, the gene for each class I MHC antigen is an admixture of coding and noncoding segments interspersed with each other. Thus, the status of noncoding segments should be clarified in relation to the concept of the primordial building block. The published 4,122 base-long sequence of human pHLA 12.4 germline gene afforded me an opportunity for clarification. Since the number of recurring base oligomers residing within the entire 4,000 + base-long sequence proved unmanageably numerous, the two portions 1,200 bases in the total length were singled out. Within these portions containing five noncoding and four coding segments, noncoding and coding segments shared 1 nonomer, 3 octamers, 6 heptamers and 5 hexamers; all the above-noted base oligomers were derived from different parts of the same 45 base-long primordial building block. It was thus concluded that not only the coding segments, but the entire ancestral gene for class I MHC antigens evolved from tandem repeats of the 45-base-long primordial building block. This new concept of primordial building block was discussed in relation to the mechanism of evolution by gene duplication.

Base Sequence↗
PubMed1999

Semantic based concept differential retrieval & equivalence detection in clinical terms version 3 (Read Codes).

Modern clinical terminologies are required to provide a large corpus of concepts to cover the complexity of medicine. It is well recognised that sufficient scalability is likely to be achieved only with those schemes that can build post-coordinated constructs compositionally. Clinical Terms Version 3 (Read Codes) uses a system of templates to both express the semantic definition (atoms) of concepts and to allow qualification of core concepts with additional detail. This common mechanism for expressing both intrinsic semantic information and additional information allows both pre- and post-coordinated concepts to be retrieved from different perspectives and to detect equivalence between alternative representations of the same concept. The practical application and experience of such an approach is described in relation to a live clinical database (Diabeta). The merits of such an approach are outlined and its relationship to other documented mechanisms outlined.

Classification↗
PubMed1993

New regulations on water hygiene. Have you applied them?

1. New legislation asks for a named manager to be responsible for water hygiene in buildings. 2. Two reports outline what is required. One, A Code of Practice, lays down a management framework. The other, a Guidance Note HS(G)/70 gives useful background information and proposes in detail what is expected. Valuable practical suggestions for existing plant are given too. 3. Every building should by now have a written risk analysis together with a description of the actions planned to minimise the risk of legionellosis (legionnaires disease or Pontiac fever). 4. Every building should by now have a written and signed log of its actions. 5. A summary of the actions required is shown at Figs 1 and 2.

Guidelines as Topic↗
PubMed2005

Conversation analysis, doctor-patient interaction and medical communication.

INTRODUCTION: This paper introduces medical educators to the field of conversation analysis (CA) and its contributions to the understanding of the doctor-patient relationship. THE CONVERSATION ANALYSIS APPROACH: Conversation analysis attempts to build bridges both to the ethnographic and the coding and quantitative studies of medical interviews, but examines the medical interview as an arena of naturally occurring interaction. This implies distinctive orientations and issues regarding the analysis of doctor-patient interaction. We discuss the CA approach by highlighting 5 basic features that are important to the enterprise, briefly illustrating each issue with a point from research on the medical interview. These features of conversation analytic theory and method imply a systematic approach to the organisation in interaction that distinguishes it from studies that rely on anecdote, ethnographic inquiry or the systematic coding of utterances. CONVERSATION ANALYSIS AND THE MEDICAL INTERVIEW: We then highlight recent CA studies of the "phases" of the internal medicine clinic and the implications of these studies for medical education. We conclude with suggestions for how to incorporate CA into the medical curriculum. It fits with biopsychosocial, patient-centred and relationship-centred approaches to teaching about medical communication.

Communication↗
PubMed2003

The biphenyl- and 4-chlorobiphenyl-catabolic transposon Tn4371, a member of a new family of genomic islands related to IncP and Ti plasmids.

The nucleotide sequence of the biphenyl catabolic transposon Tn4371 has been completed and analyzed. It confirmed that the element has a mosaic structure made of several building blocks. In addition to previously identified genes coding for a tyrosine recombinase related to phage integrases and for biphenyl degradation enzymes very similar to those of Achromobacter georgiopolitanum KKS102, Tn4371 carries many plasmid-related genes involved in replication, partition, and other, as-yet-unknown, plasmid functions. One gene cluster contains most of the genes required to express a type IV secretion-mating pair formation apparatus coupled with a TraG ATPase, all of which are related to those found on IncP and Ti plasmids. Orthologues of all Tn4371 plasmid-related genes and of the tyrosine recombinase gene were found, with a very similar organization, in the chromosome of Ralstonia solanacearum and on the yet-to-be-determined genomic sequences of Erwinia chrysanthemi and Azotobacter vinelandii. In each of these chromosomal segments, conserved segments were separated by different groups of genes, which also differed from the Tn4371 bph genes. The conserved blocks of genes were also identified, in at least two copies, in the chromosome of Ralstonia metallidurans CH34. Tn4371 thus appears to represent a new family of potentially mobile genomic islands with a broad host range since they reside in a wide range of soil proteobacteria, including plant pathogens.

Base Sequence↗
PubMed2004

A cis-acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for hepatitis C virus RNA replication.

RNA structures play key roles in the replication of RNA viruses. Sequence alignment software, thermodynamic RNA folding programs, and classical comparative phylogenetic analysis were used to build models of six RNA elements in the coding region of the hepatitis C virus (HCV) RNA-dependent RNA polymerase, NS5B. The importance of five of these elements was evaluated by site-directed mutagenesis of a subgenomic HCV replicon. Mutations disrupting one of the predicted stem-loop structures, designated 5BSL3.2, blocked RNA replication, implicating it as an essential cis-acting replication element (CRE). 5BSL3.2 is about 50 bases in length and is part of a larger predicted cruciform structure (5BSL3). As confirmed by RNA structure probing, 5BSL3.2 consists of an 8-bp lower helix, a 6-bp upper helix, a 12-base terminal loop, and an 8-base internal loop. Mutational analysis and structure probing were used to explore the importance of these features. Primary sequences in the loops were shown to be important for HCV RNA replication, and the upper helix appears to serve as an essential scaffold that helps maintain the overall RNA structure. Unlike certain picornavirus CREs, whose function is position independent, 5BSL3.2 function appears to be context dependent. Understanding the role of 5BSL3.2 and determining how this new CRE functions in the context of previously identified elements at the 5' and 3' ends of the RNA genome should provide new insights into HCV RNA replication.

Base Sequence↗
PubMed1999

Scalability problems of simple genetic algorithms.

Scalable evolutionary computation has become an intensively studied research topic in recent years. The issue of scalability is predominant in any field of algorithmic design, but it became particularly relevant for the design of competent genetic algorithms once the scalability problems of simple genetic algorithms were understood. Here we present some of the work that has aided in getting a clear insight in the scalability problems of simple genetic algorithms. Particularly, we discuss the important issue of building block mixing. We show how the need for mixing places a boundary in the GA parameter space that, together with the boundary from the schema theorem, delimits the region where the GA converges reliably to the optimum in problems of bounded difficulty. This region shrinks rapidly with increasing problem size unless the building blocks are tightly linked in the problem coding structure. In addition, we look at how straightforward extensions of the simple genetic algorithm-namely elitism, niching, and restricted mating are not significantly improving the scalability problems.

Algorithms↗
PubMed2004

Using 3D Hidden Markov Models that explicitly represent spatial coordinates to model and compare protein structures.

BACKGROUND: Hidden Markov Models (HMMs) have proven very useful in computational biology for such applications as sequence pattern matching, gene-finding, and structure prediction. Thus far, however, they have been confined to representing 1D sequence (or the aspects of structure that could be represented by character strings). RESULTS: We develop an HMM formalism that explicitly uses 3D coordinates in its match states. The match states are modeled by 3D Gaussian distributions centered on the mean coordinate position of each alpha carbon in a large structural alignment. The transition probabilities depend on the spread of the neighboring match states and on the number of gaps found in the structural alignment. We also develop methods for aligning query structures against 3D HMMs and scoring the result probabilistically. For 1D HMMs these tasks are accomplished by the Viterbi and forward algorithms. However, these will not work in unmodified form for the 3D problem, due to non-local quality of structural alignment, so we develop extensions of these algorithms for the 3D case. Several applications of 3D HMMs for protein structure classification are reported. A good separation of scores for different fold families suggests that the described construct is quite useful for protein structure analysis. CONCLUSION: We have created a rigorous 3D HMM representation for protein structures and implemented a complete set of routines for building 3D HMMs in C and Perl. The code is freely available from http://www.molmovdb.org/geometry/3dHMM, and at this site we also have a simple prototype server to demonstrate the features of the described approach.

Algorithms↗
PubMed2006

Physical models and limits of radionuclides for decorative building materials.

In the past, the external exposure dose model for soil (the soil's physical model) was used to calculate the doses of decorative building materials because there was no materials model. In this paper, physical models are proposed to calculate the absorbed dose rates in air from decorative building materials by Monte Carlo simulation with the EGSnrc code. The physical models of this paper greatly differ from physical models for soil. The good agreement between simulations and measured absorbed dose rate in indoor air indicates that the results obtained by the Monte Carlo simulations are realistic. The absorbed dose rates in air calculated by physical models for soil are much higher than the measured dose rates. According to the reports of UNSCEAR 2000 and ICRP 1999, the limits of radionuclides in some kinds of decorative building materials were deduced by using the physical models for materials presented in our work. The limits of every kind of decorative building material from our work are different.

Air Pollution, Indoor↗
PubMed1987

Information theory and the genetic code.

The genetic code, which directs the protein biosynthesis, is an information system. Although all its details are not known at present, its essential characteristics are elucidated, as well for the replication or transcription as for the translation of the genetic message. A coherent picture now appears, which reveals the existence of an universal structure, the most fundamental features of which seem to obey some logic. A systematic approach has been devised, which aims to their integration in a theorectical scheme: many features of the code table can thus be interpreted as resulting from a unique principle of best resistance against the effects of mutations. Any group of triplets or amino-acids can be considered along this line. It is more difficult however, to analyse the coexistence of two (or more) different groups. In this work, we propose to extend our optimization principle into a more general one, which includes the notion of information as defined by Shannon. We explore some consequences of this new principle in the most simple models that one can build for the origin and evolution of the genetic code.

Genetic Code↗
PubMed2001

A comparison of marital interaction patterns between couples in which the husband does or does not have Alzheimer's disease.

UNLABELLED: Objectives. Our main purpose was to examine similarities and differences in patterns of interpersonal interaction between Alzheimer's disease (AD) caregiving and noncaregiving couples (n = 54). Methods. Twenty-seven wives caring for moderately impaired husbands with probable AD and 27 noncaregiving wives from comparable sociodemographic backgrounds were videotaped in their homes during both mealtime and a future event planning task. In addition, they completed self-report questionnaires to assess depression, stress, relationship mutuality, and perceived hope. Results. Compared with their counterparts, caregiving wives reported higher levels of depression and stress, but similar shared values and closeness. For the three factors developed from the Marital Interaction Coding System (MICS, version IV; Supportive Facilitative, and Rapport Building), a complex pattern of results was found in which disease status, type of task, and gender interacted significantly. Noncaregiving couples were more interactive overall and expressed more support to each other. Caregiving wives were found to be most facilitative during the planning task, whereas AD husbands were highest on interactions that built rapport (e.g., smiling) during that same task. Caregiving wives actually increased their facilitative behavior from the mealtime to planning task, probably reflecting the increased demand characteristics of the latter. DISCUSSION: This study is one of a small body of literature to describe the negative impact of AD on spousal communication as observed and coded in two videotaped interaction situations in the home. Suggestions are made for future research, including the inclusion of longitudinal designs and non-Caucasian couples.

Adaptation, Psychological↗
PubMed2005

Effects of internal and external scatter on the build-up characteristics of Monte Carlo calculated absorbed dose for electron irradiation.

The effects of internal and external scatter on surface, build-up and depth dose characteristics simulated by Monte Carlo code EGSnrc for varying field size and SSD for a 10 MeV monoenergetic electron beam with and without an accelerator model are extensively studied in this paper. In particular, sub-millimetre surface PDD was investigated. The percentage depth doses affected significantly by the external scatter show a larger build-up dose. A forward shifted Dmax depth and a sharper fall-off region compared to PDDs with only internal scatter considered. The surface dose with both internal and external scatter shows a marked decrease at 110 cm SSD, and then slight further changes with the increasing SSD since few external scattered particles from accelerator model can reach the phantom for large SSDs. The sharp PDD increase for the 5 cm x 5 cm field compared to other fields seen when only internal scatter is considered is significantly less when external scatter is also present. The effect of external scatter on surface PDD is more pronounced for large fields than small fields (5 cm x 5 cm field).

Algorithms↗
PubMed1998

Creating proactive interference in immediate recall: building a dog from a dart, a mop, and a fig.

Phonemic codes are accorded a privileged role in most current models of immediate serial recall, although their effects are apparent in short-term proactive interference (PI) effects as well. The present research looks at how assumptions concerning distributed representation and distributed storage involving both semantic and phonemic codes might be operationalized to produce PI in a short-term cued recall task. The four experiments reported here attempted to generate the phonemic characteristics of a nonrhyming, interfering foil from unrelated filler items in the same list. PI was observed when a rhyme of the foil was studied or when the three phonemes of the foil were distributed across three studied filler items. The results suggest that items in short-term memory are stored in terms of feature bundles and that all items are simultaneously available at retrieval.

Adult↗
PubMed1989

Model for simulating the effects of management practices on pesticide concentrations in groundwater.

This manuscript describes the RUSTIC model and presents the results of an example application. RUSTIC links three subordinate models in order to predict pesticide fate and transport through the crop root zone, unsaturated zone, and saturated zone to drinking water wells: PRZM, VADOFT, and SAFTMOD. PRZM is a one-dimensional finite-difference model which accounts for pesticide fate and transport in the crop root zone. This release of PRZM incorporates several features in addition to those simulated in the original PRZM code: specifically, soil temperature simulation, volatilization and vapor phase transport in soils, irrigation simulation and a method of characteristics (MOC) algorithm to eliminate numerical dispersion. PRZM is now capable of simulating fate and transport of the parent compound and up to two daughter species. VADOFT is a one-dimensional finite-element code which solves the Richard's equation for flows in the unsaturated zone. The user may make use of constitutive relationships between pressure, water content, and hydraulic conductivity to solve the flow equations. VADOFT may also simulate the fate and transport of two parent and two daughter products. SAFTMOD is a two-dimensional finite-element model which simulates saturated solute flow and transport in either an X-Y or X-Z configuration. The codes are linked together with the aid of a flexible execution supervisor which allows the user to build models which are tailored to site-specific situations. In order to perform exposure assessments, the code is equipped with a Monte Carlo pre- and post-processor. The application of the model is to a potato field on Long Island, New York. The results indicate that RUSTIC is capable of realistically matching data observed in downgradient monitoring wells following 3 years of aldicarb application.

Aldicarb↗
PubMed1999

Monte Carlo calculations of the ionization chamber wall correction factors for 192Ir and 60Co gamma rays and 250 kV x-rays for use in calibration of 192Ir HDR brachytherapy sources.

As in the method for the calibration of 192Ir high-dose-rate (HDR) brachytherapy sources, the ionization chamber wall correction factor A(w), is needed for 192Ir and 60Co gamma rays and 250 kV x-rays. This factor takes into account the variation in chamber response due to the attenuation of the photon beam in the chamber wall and build-up cap and the contribution of scattered photons. Monte Carlo calculations were performed using the EGS4 code system with the PRESTA algorithm, to calculate the A(w) factor for 51 commercial ionization chambers and build-up caps exposed to the typical energy spectrum of 192Ir and 60Co gamma rays and 250 kV x-rays. The calculated A(w) correction factors for 192Ir and 60Co sources and 250 kV x-rays agree very well to within 0.1% with published experimental data (the statistical uncertainty is less than 0.1% of the calculated correction factor value). For the 192Ir sources, A(w) varies from 0.973 to 0.993 and for the 250 kV x-rays the minimum value of A(w) for all chambers studied is 0.983. The calculated A(w) correction factors can be used to calculate the air kerma calibration factor of HDR brachytherapy sources, when interpolative methods are considered, contributing to the reduction in the overall uncertainties in the calibration procedure.

Brachytherapy↗