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Recent experiments characterized individual neurons in the human medial temporal lobe with remarkably selective, invariant, and explicit responses to images of famous individuals or landmark buildings. Here, we used a probabilistic analysis to show that these data are consistent with a sparse code in which neurons respond in a selective manner to a small fraction of stimuli.
During the evolution of echinoderm mitochondrial (mt) DNA, a transfer RNA gene lost its tRNA function and became part of a protein-coding gene. To examine the evolutionary consequences of this event, we sequenced 961 bp of mtDNA in five sea urchin species. This enabled us to build a tree relating the mtDNAs and use it for analyzing the pattern and process of evolutionary substitutions in the former leucine tRNA gene, which now is a 5' extension of the gene for NADH dehydrogenase subunit 5 (ND5). This 5' extension is now evolving at the same rate and under the same protein-coding constraints as the rest of ND5. The adjacent (upstream) serine tRNA gene, however, has been evolving at a reduced rate, consistent with the possibility that it has assumed a punctuation role in processing of the primary transcript that was once fulfilled by the former leucine tRNA gene.
Serine carboxypeptidases (SCPs) comprise a large family of protein hydrolyzing enzymes and have roles ranging from protein turnover and C-terminal processing to wound responses and xenobiotic metabolism. The proteins can be classified into three groups, namely carboxypeptidase I, II and III, based on their coding protein sequences and the fact that each family is characterized by a central catalytic domain of unique topology designated as the "alpha/beta hydrolase fold". The available SCP protein sequences have been utilized as datasets to build a HMM (hidden Markov model) profile, which is used to search the rice (Oryza sativa L. ssp. japonica) proteome. A total of 71 SCP and serine carboxypeptidase-like (SCPL) protein-coding genes exist in rice. The intron-exon structure, chromosome localization, expression and characteristics of encoded protein sequences of the 71 putative genes are reviewed.
This paper describes general principles and example results of a new software tool being developed for physiologically-based modelling of biomedical systems within a multidisciplinary framework. The aim is to overcome some limitations of currently available software designed either for general purpose or for highly specialised modelling applications. In fact, general purpose tools usually impose explicit coding of mathematical model equations or non-intuitive system representations, whereas specialised software use domain-specific notations that allow efficient and convenient model building only for special classes of systems. The aim of the present study is to pursue intuitive representation of various, possibly interacting, types of biological systems described as interconnected physical components, such as mass and energy storage elements, active and passive transport or biochemical transformations. The presented software generates automatically the mathematical model equations that can be coded in different formats. This allows interoperability with other existing software, e.g. for numerical simulation, symbolic analysis or text processing. A multi-domain structural language has been defined for an intuitive, hierarchical and self-explanatory specification of physiological models. The proposed strategies may become useful for dissemination and integration of multidisciplinary modelling knowledge.
This paper presents values for density and mass attenuation coefficient of building materials commonly used in Brazil. Transmission measurements were performed to provide input information for simulations with MCNP4B code. The structure for the clay bricks was simulated as a mix of all material layers and an effective density determined. The mass attenuation coefficients were determined for the 50-3,000 keV gamma-ray energy range. A comparison with results for similar materials found in the literature showed good agreement.
The 3D models of both CB1 and CB2 human receptors have been established by homology modeling using as template the X-ray structure of bovine Rhodopsin (code pdb: 1F88) a G-protein-coupled receptor (GPCR). A recursive approach comprising sequence alignment and model building was used to build both models, followed by the refinement of non-conserved regions. The cannabinoid system has been studied by means of docking techniques, using the 3D models of both CB1 and CB2 and well known reference inverse agonist/antagonist compounds. An approach based on the flexibility of the structures has been used to model the receptor-ligand complexes. The structural effects of ligand binding were studied and analyzed on the basis of hydrogen bond interactions, and binding energy calculations. Potential interaction sites of the receptor were determined from analysis of the difference accessible surface area (DASA) study of the protein with and without ligand.
The antigen 85 complex of Mycobacterium tuberculosis consists of three abundantly secreted proteins. The recent characterization of a mycoloyltransferase activity associated in vitro with each of these antigens suggested that they are potentially important for the building of the unusual cell envelope of mycobacteria. To define the physiological role of these proteins, the gene coding for antigen 85C was inactivated by transposon mutagenesis. The resulting mutant was shown to transfer 40% fewer mycolates to the cell wall with no change in the types of mycolates esterifying arabinogalactan or in the composition of non-covalently linked mycolates. As a consequence, the diffusion of the hydrophobic chenodeoxycholate and the hydrophilic glycerol, but not that of isoniazid, was found to be much faster through the cell envelope of the mutant than that of the parent strain. Taken together, these data demonstrate that: (i) antigen 85C is involved directly or indirectly in the transfer of mycolates onto the cell wall of the whole bacterium; (ii) the enzyme is not specific for a given type of mycolate; and (iii) the cell wall-linked mycolate layer may represent a barrier for the diffusion of small hydrophobic and hydrophilic molecules.
We present COMPUCELL3D, a software framework for three-dimensional simulation of morphogenesis in different organisms. COMPUCELL3D employs biologically relevant models for cell clustering, growth, and interaction with chemical fields. COMPUCELL3D uses design patterns for speed, efficient memory management, extensibility, and flexibility to allow an almost unlimited variety of simulations. We have verified COMPUCELL3D by building a model of growth and skeletal pattern formation in the avian (chicken) limb bud. Binaries and source code are available, along with documentation and input files for sample simulations, at http:// compucell.sourceforge.net.
Building on the work of previous authors, the Computer-based Patient Record Institute (CPRI) Work Group on Codes and Structures has described features of a classification scheme for implementation within a computer-based patient record. The authors of the current study reviewed the evaluation literature related to six major nursing vocabularies (the North American Nursing Diagnosis Association Taxonomy 1, the Nursing Interventions Classification, the Nursing Outcomes Classification, the Home Health Care Classification, the Omaha System, and the International Classification for Nursing Practice) to determine the extent to which the vocabularies include the CPRI features. None of the vocabularies met all criteria. The Omaha System, Home Health Care Classification, and International Classification for Nursing Practice each included five features. Criteria not fully met by any systems were clear and non-redundant representation of concepts, administrative cross-references, syntax and grammar, synonyms, uncertainty, context-free identifiers, and language independence.
BACKGROUND: The drug treatment field tends to place emphasis on the individual rather than the individual in social context. While there are a growing number of studies indicating that drug-using intimate partners are likely to play an important role in determining treatment options, little attention has been given to the experience and complex treatment needs of illicit drug-using (heroin, cocaine, crack) couples. METHODS: This exploratory study used in-depth interviews and ethnographic engagement to better understand the relationship between interpersonal dynamics and the treatment experience of ten relatively stable drug-using couples in Hartford, CT. Semi-structured and open-ended qualitative interviews were conducted with each couple and separately with each partner. Whenever possible, the day-to-day realities and contexts of risk were also observed via participant and non-participant observation of these couples in the community. A grounded theory approach was used to inductively code and analyze nearly 40 transcripts of 60-90 minute interviews as well as fieldnotes. RESULTS: This study builds on a concept of complex interpersonal dynamics among drug users. Interpersonal dynamics of care and collusion were identified: couples cared for each other and colluded to acquire and use drugs. Care and collusion operate at the micro level of the risk environment. Treatment barriers and inadequacies were identified as part of the risk environment at the meso or intermediate level of analysis, and larger social forces such as gender dynamics, poverty and the "War on Drugs" were identified at the macro level. Interpersonal dynamics posed problems for couples when one or both partners were interested in accessing treatment. Structural barriers presented additional obstacles with the denial of admittance of both partners to treatment programs which had a sole focus on the individual and avoided treating couples. CONCLUSION: Detoxification and treatment facilities need to recognize the complex interplay between interpersonal dynamics which shape the treatment experience of couples, and which are also shaped by larger structural dynamics, including barriers in the treatment system. Improvements to the treatment system in general will go a long way in improving treatment for couples. Couples-specific programming also needs to be developed.
Retrovirus-derived gene transfer systems (retroviral vectors) are the most commonly used gene transfer tools in modern biology. They have been used to study various aspects of retroviral replication, the organization and function of oncogenes and other eucaryotic genes, and, recently, to transduce therapeutic genes to cure inborn errors of metabolism, cancer, AIDS, and many other diseases in man. Highly oncogenic retroviruses served as a model for the construction of artificial retroviral gene transfer systems. These viruses carry a non-viral gene in their genome in addition or substituting for viral protein coding sequences. The replication of such defective retroviruses depends on the presence of a wild-type-virus, which supplies all proteins in trans for particle assembly and infection of a new target cell. Thus, highly oncogenic retroviruses can be considered as naturally occurring gene transfer vectors. Following this principle, cell lines have been constructed which express retroviral protein coding sequences from plasmid DNAs and which contain a viral genome in which the protein coding sequences have been replaced with a gene of interest. This article describes the history, principles, and basic building blocks of first and modern retrovirus-derived gene transfer systems.
Based on hidden Markov models (HMM), the paper utilized reported SCP (Serine Carboxypeptidases) protein sequences as datasets to build HMM profile. To search Arabidopsis thaliana whole proteome,and identified 54 SCPL (Serine Carboxypeptidase-Like) proteins coding genes. The intron-exon structure, the chromosome mapping and the characteristic of coded protein sequences of those 54 putative genes were analyzed in details, revealing seven gene clusters probably resulted from recent gene duplication. This implied that a remarkable number of Arabidopsis thaliana SCPL genes are harboring alternative splice sites. Phylogenetics evolution analysis suggested 88.9% proteins encoded by Arabidopsis genes belong to two string subfamily of carboxypeptidase, I or II, while only 11.1% proteins fall into single string carboxypeptidase III subfamily. Our results indicated besides the facts that all enzymes of this family contained a central catalytic domain of unique topology and three dimensional structure designated as "alpha/beta hydrolase fold", the DNA and their encoded protein sequences also gave clues to phylogentics studies.
Tonotopy and synchronization of spike discharges with the stimulus frequency are two modes of coding which are probably not independent. After defining an appropriate process of coding and a measure of temporal correlations between two neighbouring channels, we show that it is possible to build with these two fundamental features of the auditory system, a neurophysiologically plausible neural network which has properties of noise resistance and signal segmentation.
With few exceptions the genetic codes of all known organisms encode the same 20 amino acids, yet all that is required to add a new building block are a unique tRNA/aminoacyl-tRNA synthetase pair, a source of the amino acid, and a unique codon that specifies the amino acid. For example, the amber nonsense codon, TAG, together with orthogonal Methanococcus jannaschii or Escherichia coli tRNA/synthetase pairs have been used to genetically encode a variety of unnatural amino acids in E. coli and yeast, respectively. However, the availability of noncoding triplet codons ultimately limits the number of amino acids encoded by any organism. Here, we report the design and generation of an orthogonal synthetase/tRNA pair derived from archaeal tRNA(Lys) sequences that efficiently and selectively incorporates an unnatural amino acid into proteins in response to the quadruplet codon, AGGA. Frameshift suppression with L-homoglutamine (hGln) does not significantly affect protein yields or cell growth rates and is mutually orthogonal with amber suppression, permitting the simultaneous incorporation of two unnatural amino acids, hGln and O-methyl-L-tyrosine, at distinct positions within myoglobin. This work suggests that neither the number of available triplet codons nor the translational machinery itself represents a significant barrier to further expansion of the genetic code.
Here we present a model of nucleotide substitution in protein-coding regions that also encode the formation of conserved RNA structures. In such regions, apparent evolutionary context dependencies exist, both between nucleotides occupying the same codon and between nucleotides forming a base pair in the RNA structure. The overlap of these fundamental dependencies is sufficient to cause "contagious" context dependencies which cascade across many nucleotide sites. Such large-scale dependencies challenge the use of traditional phylogenetic models in evolutionary inference because they explicitly assume evolutionary independence between short nucleotide tuples. In our model we address this by replacing context dependencies within codons by annotation-specific heterogeneity in the substitution process. Through a general procedure, we fragment the alignment into sets of short nucleotide tuples based on both the protein coding and the structural annotation. These individual tuples are assumed to evolve independently, and the different tuple sets are assigned different annotation-specific substitution models shared between their members. This allows us to build a composite model of the substitution process from components of traditional phylogenetic models. We applied this to a data set of full-genome sequences from the hepatitis C virus where five RNA structures are mapped within the coding region. This allowed us to partition the effects of selection on different structural elements and to test various hypotheses concerning the relation of these effects. Of particular interest, we found evidence of a functional role of loop and bulge regions, as these were shown to evolve according to a different and more constrained selective regime than the nonpairing regions outside the RNA structures. Other potential applications of the model include comparative RNA structure prediction in coding regions and RNA virus phylogenetics.
It has been shown in several studies that the build-up in photon beams behind air cavities (such as in the head and neck) increases with energy. In this study this effect is investigated over a broad range of energies that have been used for treating head and neck tumours. The study addresses the question of whether an energy lower than 6 MV is desirable and is based on measurements and Monte Carlo (MC) simulations. In a PMMA phantom containing an air cavity (3 x 16 x 3 cm3 at 3 cm depth) an ionization chamber (Capintec PS-033) was used to measure the dose build-up behind the cavity for 4, 6 and 8 MV beam qualities for different field sizes (from 3 x 6 cm2 to 8 x 8 cm2). MC simulations were made using the EGSnrc code for the same geometry and energies as well as for Co-60. Measurements and MC simulations agree well when the fixed-separation plane-parallel chamber measurements have been corrected for the expected over-response in the build-up region. This work demonstrates that the build-up effect of 6 MV is 'closer' to the build-up effect of 8 MV than to that of 4 MV. This suggests that if the build-up effect is of concern when the target volume is in the vicinity of air cavities, 4 MV should be preferred over both 6 MV and 8 MV. This work also shows that the build-up effect for Co-60 is significantly smaller than that of 4 MV. Moreover, the build-up effect increases as the field size decreases. With the increasing use of IMRT (and radiosurgery), small fields are used more frequently making these issues even more relevant. This should be taken into consideration when choosing the accelerator energies for a radiotherapy department.
An iterative process for improving the completeness and quality of atomic models automatically built at moderate resolution (up to about 2.8 A) is described. The process consists of cycles of model building interspersed with cycles of refinement and combining phase information from the model with experimental phase information (if any) using statistical density modification. The process can lead to substantial improvements in both the accuracy and completeness of the model compared with a single cycle of model building. For eight test cases solved by MAD or SAD at resolutions ranging from 2.0 to 2.8 A, the fraction of models built and assigned to sequence was 46-91% (mean of 65%) after the first cycle of building and refinement, and 78-95% (mean of 87%) after 20 cycles. In an additional test case, an incorrect model of gene 5 protein (PDB code 2gn5; r.m.s.d. of main-chain atoms from the more recent refined structure 1vqb at 1.56 A) was rebuilt using only structure-factor amplitude information at varying resolutions from 2.0 to 3.0 A. Rebuilding was effective at resolutions up to about 2.5 A. The resulting models had 60-80% of the residues built and an r.m.s.d. of main-chain atoms from the refined structure of 0.20 to 0.62 A. The algorithm is useful for building preliminary models of macromolecules suitable for an experienced crystallographer to extend, correct and fully refine.
Federal investigations of physician billing practices will only grow more intense in 1998. Regular self audit, especially of CPT coding, can help practices stay out of the limelight. An established compliance program and high-ranking compliance officer are also becoming standard. Compliance programs should pay particular attention to "incident to" billing, level 5 E/M codes, time-based E/M codes, codes with both technical and professional component services, consultations, critical care codes and physician care plan oversight. Even group practices that use billing companies need to stay alert. Physicians are liable for the acts of the billing company whether they knew or should have known submitted claims were false.