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Temporal coding of low-frequency amplitude modulation in the torus semicircularis of the grass frog.

Single neuron responses to sinusoidal 20 Hz amplitude modulated tone bursts (612.5 ms stimulus-on time at the rate of once per 2.2 s) were studied in the auditory midbrain (torus semicircularis) of the immobilized grass frog (Rana temporaria temporaria). The characteristic frequency stimuli at 30 dB above the minimum threshold included 12 full modulation periods with fixed initial phase. Neurons generally showed good phase-locking to the envelope waveform. 160 of the 186 investigated neurons responded to 80% amplitude modulated stimuli with discharges synchronized to the modulation cycle. For this modulation depth the best phase-locking capability was observed for certain phasic and build-up units. The synchronous response to 10% modulated stimuli was observed in 104 units. Though a few (2 of 29) phasic units were capable of reproducing this modulation with very high fidelity, the general tendency was the increasing of phase-locking capacity for units with a substantial sustained activity. In this condition for 66 units (63% of the units displaying the synchronous response) we observed a significant improvement of phase-locking from the initial to the terminal periods of modulation. This effect could be interpreted as an initial stage of the enhancement of small amplitude changes in the course of the long-term adaptation.

Acoustic Stimulation↗

Organization of multispecific DNA methyltransferases encoded by temperate Bacillus subtilis phages.

B. subtilis phage rho 11s codes for a multispecific DNA methyltransferase (Mtase) which methylates cytosine within the sequences GGCC and GAGCTC. The Mtase gene of rho 11s was isolated and sequenced. It has 1509 bp, corresponding to 503 amino acids (aa). The enzyme's Mr of 57.2 kd predicted from the nucleotide sequence was verified by direct Mr determinations of the Mtase. A comparison of the aa sequence of the rho 11s Mtase with those of related phages SPR and phi 3%, which differ in their methylation potential, revealed generalities in the building plan of such enzymes. At least 70% of the aa of each enzyme are contained in two regions of 243 and 109 aa at the N and C termini respectively, which are highly conserved among the three enzymes. In each enzyme, variable sequences separate the conserved regions. Variability is generated through the single or multiple use of related and unrelated sequence motifs. We propose that the recognition of those DNA target sequences, which are unique for each of the three enzymes, is determined by these variable regions. Evolutionary relationships between the three enzymes are discussed.

Amino Acid Sequence↗

Discharge properties of identified cochlear nucleus neurons and auditory nerve fibers in response to repetitive electrical stimulation of the auditory nerve.

Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29 degrees C, we intracellularly recorded and stained cochlear nucleus (CN) neurons and auditory nerve (AN) fibers. Discharge properties of CN cells and AN axons were tested in response to 50-ms trains of electrical pulses delivered to the AN at rates ranging from 100 to 1000 pulses per second (pps). At low stimulation rates (200-300 pps), the discharges of AN fibers and a large proportion of principal cells (bushy, octopus, stellate) in the ventral cochlear nucleus (VCN) followed with high probability each pulse in the train, resulting in synchronization of discharges within large populations of AN fibers and CN cells. In contrast, at high stimulation rates (500 pps and higher), AN fibers and many VCN cells exhibited "primary-like", "onset" and some other discharge patterns resembling those produced by natural sound stimuli. Unlike cells in the VCN, principal cells (pyramidal, giant) of the dorsal CN did not follow the stimulating pulses even at low rates. Instead, they often showed "pauser" and "build-up" patterns of activity, characteristic for these cells in conditions of normal hearing. We hypothesize that, at low stimulation rates, the response behavior of AN fibers and VCN cells is different from the patterns of neuronal activity related to normal auditory processing, whereas high stimulation rates produce more physiologically meaningful discharge patterns. The observed differences in discharge properties of AN fibers and CN cells at different stimulation rates can contribute to significant advantages of high- versus low-rate electrical stimulation of the AN used for coding sounds in modern cochlear implants.

Action Potentials↗

PoInTree: a polar and interactive phylogenetic tree.

PoInTree (Polar and Interactive Tree) is an application that allows to build, visualize and customize phylogenetic trees in a polar interactive and highly flexible view. It takes as input a FASTA file or multiple alignment formats. Phylogenetic tree calculation is based on a sequence distance method and utilizes the Neighbor Joining (NJ) algorithm. It also allows displaying precalculated trees of the major protein families based on Pfam classification. In PoInTree, nodes can be dynamically opened and closed and distances between genes are graphically represented. Tree root can be centered on a selected leaf. Text search mechanism, color-coding and labeling display are integrated. The visualizer can be connected to an Oracle database containing information on sequences and other biological data, helping to guide their interpretation within a given protein family across multiple species. The application is written in Borland Delphi and based on VCL Teechart Pro 6 graphical component (Steema software).

Algorithms↗

Smoking on hospital grounds and the impact of outdoor smoke-free zones.

OBJECTIVES: To describe the type and location of smokers on the grounds of smoke-free public hospitals and to observe the impact of introducing smoke-free signs in outdoor areas of the hospital grounds. DESIGN: Observation study of outdoor smoking behaviour before and after the introduction of outdoor smoke-free signs at one hospital (H1) and at the same two time periods at a nearby control hospital (H2), which already had some outdoor smoke-free signs at Time 1. SETTING: The John Hunter Hospital (H1) in Newcastle, Australia and a nearby control hospital, Maitland Hospital (H2) in 1991. SUBJECTS: All people in defined outdoor sites of the two hospitals on seven randomly selected days over two weeks before and after the policy change were coded as either "smoker" or "non-smoker" and as either "staff", "patient", or "visitor". The number of smokers observed in each site was measured as a proportion of all smokers observed on the grounds of that hospital. INTERVENTION: Introduction of outdoor smoke-free zones and signs at H1. RESULTS: Less than 10% of observed outdoor smokers in both hospitals were patients, 40% were visitors, and more than 50% were staff. Of outdoor smokers, 82% were observed less than 10 m from entrances to the hospital building at time 1. After the introduction of signs in H1, a 4-percentage point decrease (P < 0.05) occurred in the percentage of smokers observed in smoke-free zones at time 2 (from 32% to 28%), compared with a 2-percentage point decrease (P > 0.05 at time 2 in H2 (from 48% to 46%). DISCUSSION: This observation study of smoking behaviour in hospital grounds highlights the need to reduce smoking among staff and visitors near hospital entrances. Specific strategies are discussed, which are likely to enhance compliance and hence enable the effective introduction of smoke-free policies on hospital grounds.

Hospitals↗

Escherichia coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from mevalonate: a novel system for the genetic analysis of the 2-C-methyl-d-erythritol 4-phosphate pathway for isoprenoid biosynthesis.

Isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP) constitute the basic building block of isoprenoids, a family of compounds that is extraordinarily diverse in structure and function. IPP and DMAPP can be synthesized by two independent pathways: the mevalonate pathway and the recently discovered 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway. Although the MEP pathway is essential in most eubacteria, algae and plants and has enormous biotechnological interest, only some of its steps have been determined. We devised a system suitable for the genetic analysis of the MEP pathway in Escherichia coli. A synthetic operon coding for yeast 5-diphosphomevalonate decarboxylase, human 5-phosphomevalonate kinase, yeast mevalonate kinase and E. coli isopentenyl diphosphate isomerase was incorporated in the chromosome of this bacterium. The expression of this operon allowed the synthesis of IPP and DMAPP from mevalonate added exogenously and complementation of lethal mutants of the MEP pathway. We used this system to show that the ygbP, ychB and ygbB genes are essential in E. coli and that the steps catalysed by the products of these genes belong to the trunk line of the MEP pathway.

Bacterial Proteins↗

Spatial coding of semantic information: knowledge of country and city names depends on their geographical proximity.

We report the case of a patient, A.Z., with a refractory disorder of semantic processing. Using a number of spoken word-written word matching paradigms, her comprehension of the broad proper nouns category of place names was investigated. In addition to being sensitive to temporal factors, A.Z.'s ability to identify country or city names accurately was significantly worse when selecting a target from an array of geographically close rather than distant places. The influence of geographical proximity and location was observed even when identifying proximal and distal English towns, but not with less well-known American states. These close and distant effects are attributed to the build-up of refractoriness in representations with shared neural circuitry. Our findings reveal a previously undocumented level of fine-grain organization in this domain of semantic space. It is argued that information about geographical proximity cannot be encoded in purely verbal or visual terms. Consequently, we propose the existence of a separate module of spatially encoded information within conceptual knowledge.

Acoustic Stimulation↗

Extracting knowledge from dynamics in gene expression.

Most investigations of coordinated gene expression have focused on identifying correlated expression patterns between genes by examining their normalized static expression levels. In this study, we focus on the dynamics of gene expression by seeking to identify correlated patterns of changes in genetic expression level. In doing so, we build upon methods developed in clinical informatics to detect temporal trends of laboratory and other clinical data. We construct relevance networks from Saccharomyces cerevisiae gene-expression dynamics data and find genes with related functional annotations grouped together. While some of these associations are also found using a standard expression level analysis, many are identified exclusively through the dynamic analysis. These results strongly suggest that the analysis of gene expression dynamics is a necessary and important tool for studying regulatory and other functional relationships among genes. The source code developed for this investigation is freely available to all non-commercial investigators by contacting the authors.

Cluster Analysis↗

A new member of the balbiani ring multigene family in the dipteran Chironomus tentans consists of a single-copy version of a unit repeated in other gene family members.

The known Balbiani ring (BR) multigene family members in the dipteran Chironomus tentans encode salivary gland secretory proteins in the size range between 38 and 1,000 kDa. The proteins interact to form protein fibers used by the aquatic larvae to spin feeding and protective larval tubes or pupation tubes. Here, we describe a new BR multigene family member, the sp17 gene, which codes for an 89-amino-acid-long protein with a relative mobility of 17k. The gene has a high content of charged amino acid residues and consists of two structurally different halves. Five regularly spaced cysteine codons are present in the 5' half while the 3' half contains five proline codons. These two different halves exhibit similarities to the C and SR regions, respectively, which form the tandemly repeated units in the about 40-kb-long BR genes and which also, in different versions, are the building blocks of all genes in the BR multigene family. In this multigene family, encoding interacting structural proteins, the long BR genes with their 125-150 tandemly arranged repeat units as well as the short sp17 gene with its single-copy version of such a repeat unit, have therefore evolved from a common ancestor.

Amino Acid Sequence↗

The role of consequence modeling in LNG facility siting.

Liquefied natural gas (LNG) project modeling focuses on two primary issues, facility siting and the physical layout of element spacing. Modeling often begins with an analysis of these issues, while ensuring code compliance and sound engineering practice. The most commonly performed analysis involves verifying compliance with the siting provisions of NFPA 59A, which primarily concern property-line spacing (offsite hazard impacts). If the facility is located in the US, compliance with 49 CFR 193 is also required. Other consequence modeling is often performed to determine the spacing of elements within the facility (onsite hazard impacts). Often, many issues concerning in-plant spacing are addressed with the guidance provided in Europe's LNG standard, EN-1473. Spacing of plant buildings in relation to process areas is also a concern as analyzed using the approach given in API RP 752. Studies may also include probabilistic analysis, depending on the perceived risk and cost of mitigation.

Accidents↗

A requirement for anaerobically induced redox functions during aerobic growth of Escherichia coli with serine, glycine and leucine as carbon source.

Escherichia coli strains with mutations in 3 genes coding for redox functions--torA, nuoM and glpC--are able to grow with pyruvate as carbon source, but are not able to use a combination of serine, glycine and leucine as carbon source, unlike the parent strain which uses either. All three mutants are able to produce and activate L-serine deaminase (L-SD) when grown in glucose minimal medium, and thus should be able to convert serine to pyruvate and grow on it. We suggest that activation of L-SD involves specific chemical reactions, perhaps building an Fe-S cluster. Mutant cells can carry out the necessary reaction to activate L-SD when grown in glucose minimal medium but apparently cannot do so when grown in SGL medium.

Anaerobiosis↗

Overseer: a nucleotide sequence searching tool.

Overseer is a computer program that searches databases of nucleic acid sequences for objects of interest to the user. Such objects may consist of any number of simpler building blocks such as repeats, palindromes or stem-loops, strings of particular bases with or without mismatches, etc. Written in standard Pascal, this program runs under Unix and VMS and should also run under other operating systems. A simple interface allows the user to generate interactively a file containing a description of the target to be found. The searching program runs non-interactively, processing the information from the file and searching the sequences. The results are output to a file. Search capabilities are quite flexible and the code is designed to be modified. Since the framework of the program is simple, adding new modules to search for new target types as the need arises is possible.

Algorithms↗

[History of Hansen's disease control policy in the United States].

Federal government set up the institutions for the study and treatment of Hansen's disease patients in Hawaii in 1905. Then in 1917, a legislation was made to build a national leprosarium (leper home), authorize the Surgeon General (SG) to receive into that institution any person afflicted with leprosy who presents himself or herself for care, detention, and treatment, or any person afflicted with leprosy duly consigned to said home by the proper health authorities. The National Leprosarium (later renamed as National Hansen's Disease Center) opened in Carville in 1922. Although promin treatment had started in the early 1940s, the Public Health Service Act of 1944 retained the SG's authority for detention and apprehension. Discharge codes were gradually loosened since then, but the efforts to revise the Act were never successful for a long time. It was in 1985 when the Act was abolished. Provision of long-term care for new patients at the Center was terminated finally in 1997.

Communicable Disease Control↗

A framework for building and simulating qualitative models of compartmental systems.

This paper describes a framework, called QCMF (Qualitative Compartmental Modeling Framework), which assists the user in formulating models of a pathophysiological system and in analyzing their behaviors through the simulation of the effects of a variety of pathogenetic mechanisms and therapeutical treatments. QCMF has adopted the compartmental theory as modeling ontology: a system is represented as a finite set of interacting compartments. The user enters, through an iconic language and menus, the compartmental structure of a pathophysiological system and the definition of the kinds of functional relationships describing the interactions between compartments. Then, QCMF automatically generates a behavior model of the system. Such a model consists of a set of ordinary differential equations, which are qualitatively expressed, and is directly coded into the language which is interpreted by the simulation algorithm. The system behavior can be obtained by simulating the model starting from an initial state which describes the perturbations acting on the system. The code defining the initial state is automatically built by QCMF as well. Finally, explanations of the predicted behavior are also automatically generated.

Algorithms↗

The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium.

We used overlapping and nested homozygous deletions, contig building, genomic sequencing, and physical and transcript mapping to further define a approximately 630-kb lung cancer homozygous deletion region harboring one or more tumor suppressor genes (TSGs) on chromosome 3p21.3. This location was identified through somatic genetic mapping in tumors, cancer cell lines, and premalignant lesions of the lung and breast, including the discovery of several homozygous deletions. The combination of molecular manual methods and computational predictions permitted us to detect, isolate, characterize, and annotate a set of 25 genes that likely constitute the complete set of protein-coding genes residing in this approximately 630-kb sequence. A subset of 19 of these genes was found within the deleted overlap region of approximately 370-kb. This region was further subdivided by a nesting 200-kb breast cancer homozygous deletion into two gene sets: 8 genes lying in the proximal approximately 120-kb segment and 11 genes lying in the distal approximately 250-kb segment. These 19 genes were analyzed extensively by computational methods and were tested by manual methods for loss of expression and mutations in lung cancers to identify candidate TSGs from within this group. Four genes showed loss-of-expression or reduced mRNA levels in non-small cell lung cancer (CACNA2D2/alpha2delta-2, SEMA3B [formerly SEMA(V), BLU, and HYAL1] or small cell lung cancer (SEMA3B, BLU, and HYAL1) cell lines. We found six of the genes to have two or more amino acid sequence-altering mutations including BLU, NPRL2/Gene21, FUS1, HYAL1, FUS2, and SEMA3B. However, none of the 19 genes tested for mutation showed a frequent (>10%) mutation rate in lung cancer samples. This led us to exclude several of the genes in the region as classical tumor suppressors for sporadic lung cancer. On the other hand, the putative lung cancer TSG in this location may either be inactivated by tumor-acquired promoter hypermethylation or belong to the novel class of haploinsufficient genes that predispose to cancer in a hemizygous (+/-) state but do not show a second mutation in the remaining wild-type allele in the tumor. We discuss the data in the context of novel and classic cancer gene models as applied to lung carcinogenesis. Further functional testing of the critical genes by gene transfer and gene disruption strategies should permit the identification of the putative lung cancer TSG(s), LUCA, Analysis of the approximately 630-kb sequence also provides an opportunity to probe and understand the genomic structure, evolution, and functional organization of this relatively gene-rich region.

Carcinoma, Non-Small-Cell Lung↗

SVLM21, a mutant of Sindbis virus able to grow in Aedes albopictus cells in the absence of methionine, shows increased sensitivity to S-adenosylhomocysteine hydrolase inhibitors such as neplanocin A.

Inhibition of S-adenosylhomocysteine (AdoHcy) hydrolase by compounds such as Neplanocin A (NPA) leads to the build-up of AdoHcy and the inhibition of methyltransferase enzymes. Whether assayed by efficiency of plaquing or virus yield, SVLM21, a mutant of Sindbis virus resistant to methionine deprivation, was more sensitive to NPA than was the standard virus (SVstd) from which it was derived. For example, whereas 10 micrograms NPA/ml depressed the yield of SVLM21 by more than 30-fold, the yield of SVstd was not significantly affected. Similar differences in sensitivities were shown to three other compounds which inhibit AdoHcy hydrolase. These results support the idea that SVLM21 codes for an altered RNA methyltransferase.

Adenine↗

A genetic linkage map of the male goat genome.

This paper presents a first genetic linkage map of the goat genome. Primers derived from the flanking sequences of 612 bovine, ovine and goat microsatellite markers were gathered and tested for amplification with goat DNA under standardized PCR conditions. This screen made it possible to choose a set of 55 polymorphic markers that can be used in the three species and to define a panel of 223 microsatellites suitable for the goat. Twelve half-sib paternal goat families were then used to build a linkage map of the goat genome. The linkage analysis made it possible to construct a meiotic map covering 2300 cM, i.e., > 80% of the total estimated length of the goat genome. Moreover, eight cosmids containing microsatellites were mapped by fluorescence in situ hybridization in goat and sheep. Together with 11 microsatellite-containing cosmids previously mapped in cattle (and supposing conservation of the banding pattern between this species and the goat) and data from the sheep map, these results made the orientation of 15 linkage groups possible. Furthermore, 12 coding sequences were mapped either genetically or physically, providing useful data for comparative mapping.

Animals↗

A methodology for building an AIDS research file using Medicaid claims and administrative data bases.

There is a current and continuing need for health services research on the epidemiology of AIDS and its impact on health care systems. However, large data bases designed for other purposes, such as hospital discharge abstract systems and medical claims systems, are the primary source of data for AIDS research. Thus, methodologies must be developed that enable researchers to investigate AIDS using data bases designed for other purposes. In this report, we describe a methodology for utilizing Medicaid Management Information Systems (MMIS) data to conduct health services research on AIDS. We developed an ICD-9-CM diagnosis-based algorithm that accurately identified the majority of AIDS cases, both before and after AIDS-specific ICD-9-CM codes became available in October 1986. Using diagnostic categories that we had developed previously to identify AIDS cases among disabled young men in California on Medicaid, we expanded the methodology to include children, men, and women of all ages in California and New York. The algorithm worked best with young disabled males, older males, and females between 18 and 50 years of age. The algorithm worked least well with nondisabled males, females over age 50 years, and children. We also developed methodologies for defining Medicaid AIDS onset, risk group, and date of death. Our research resulted in the identification of a study population representing the majority of Medicaid AIDS cases between 1983 and 1986 in California and New York. The AIDS study population data base was used in further research on eligibility patterns, the epidemiology of the AIDS epidemic, lifetime Medicaid utilization and expenditures, and the development of a survival-based severity index for Medicaid recipients with AIDS.

Acquired Immunodeficiency Syndrome↗