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Homology building as a means to define antigenic epitopes on dihydrofolate reductase (DHFR) from Plasmodium falciparum.

BACKGROUND: The aim of this study was to develop site-specific antibodies as a tool to capture Plasmodium falciparum-dihydrofolate reductase (Pf-DHFR) from blood samples from P. falciparum infected individuals in order to detect, in a sandwich ELISA, structural alterations due to point mutations in the gene coding for Pf-DHFR. Furthermore, we wanted to study the potential use of homology models in general and of Pf-DHFR in particular in predicting antigenic malarial surface epitopes. METHODS: A homology model of Pf-DHFR domain was employed to define an epitope for the development of site-specific antibodies against Pf-DHFR. The homology model suggested an exposed loop encompassing amino acid residues 64-100. A synthetic peptide of 37-mers whose sequence corresponded to the sequence of amino acid residues 64-100 of Pf-DHFR was synthesized and used to immunize mice for antibodies. Additionally, polyclonal antibodies recognizing a recombinant DHFR enzyme were produced in rabbits. RESULTS AND CONCLUSIONS: Serum from mice immunized with the 37-mer showed strong reactivity against both the immunizing peptide, recombinant DHFR and a preparation of crude antigen from P. falciparum infected red blood cells. Five monoclonal antibodies were obtained, one of which showed reactivity towards crude antigen prepared from P. falciparum infected red cells. Western blot analysis revealed that both the polyclonal and monoclonal antibodies recognized Pf-DHFR. Our study provides insight into the potential use of homology models in general and of Pf-DHFR in particular in predicting antigenic malarial surface epitopes.

Amino Acids↗

The Significance of SNODENT.

SNODENT is a dental diagnostic vocabulary incompletely integrated in SNOMED-CT. Nevertheless, SNODENT could become the de facto standard for dental diagnostic coding. SNODENT's manageable size, the fact that it is administratively self-contained, and relates to a well-understood domain provides valuable opportunities to formulate and test, in controlled experiments, a series of hypothesis concerning diagnostic systems. Of particular interest are questions related to establishing appropriate quality assurance methods for its optimal level of detail in content, its ontological structure, its construction and maintenance. This paper builds on previous-software-based methodologies designed to assess the quality of SNOMED-CT. When applied to SNODENT several deficiencies were uncovered. 9.52% of SNODENT terms point to concepts in SNOMED-CT that have some problem. 18.53% of SNODENT terms point to SNOMED-CT concepts do not have, in SNOMED, the term used by SNODENT. Other findings include the absence of a clear specification of the exact relationship between a term and a termcode in SNODENT and the improper assignment of the same termcode to terms with significantly different meanings. An analysis of the way in which SNODENT is structurally integrated into SNOMED resulted in the generation of 1081 new termcodes reflecting entities not present in the SNOMED tables but required by SNOMED's own description logic based classification principles. Our results show that SNODENT requires considerable enhancements in content, quality of coding, quality of ontological structure and the manner in which it is integrated and aligned with SNOMED. We believe that methods for the analysis of the quality of diagnostic coding systems must be developed and employed if such systems are to be used effectively in both clinical practice and clinical research.

Humans↗

A dosimetric study of Leipzig applicators.

PURPOSE: To obtain the absolute dose-rate distribution in liquid water for all six cup-shaped Leipzig applicators by means of an experimentally validated Monte Carlo (MC) code. These six applicators were used in high-dose-rate (HDR) afterloaders with the "classic" and v2 (192)Ir sources. The applicators have an inner diameter of 1, 2, and 3 cm, with the source traveling parallel or perpendicular to the contact surface. METHODS AND MATERIALS: The MC GEANT4 code was used to obtain the dose-rate distribution in liquid water for the six applicators and the two HDR source models. To normalize the applicator output factors, a MC simulation for the "classic" and v2 sources in air was performed to estimate the air-kerma strength. To validate this specific application and to guarantee that realistic source-applicator geometry was considered, an experimental verification procedure was implemented in this study, in accordance with the TG43U1 recommendations. Thermolumniscent dosimeter chips and a parallel plate ionization chamber in a polymethyl methacrylate (PMMA) phantom were used to verify the MC results for the six applicators in a microSelectronHDR afterloader with the "classic" source. Dose-rate distributions dependence on phantom size has been evaluated using two different phantom sizes. RESULTS: Percentage depth dose and off-axis profiles were obtained normalized at a depth of 3 mm along the central axis for both phantom sizes. A table of output factors, normalized to 1 U of source kerma strength at this depth, is presented. The dose measured in the PMMA phantom agrees within experimental uncertainties with the dose obtained by the MC GEANT4 code calculations. The phantom size influence on dose-rate distributions becomes significant at depths greater than 5 cm. CONCLUSIONS: MC-detailed simulation was performed for the Nucletron Leipzig HDR applicators. The matrix data obtained, with a grid separation of 0.5 mm, can be used to build a dataset in a convenient format to model these distributions for routine use with a brachytherapy treatment planning system.

Brachytherapy↗

Friedrich Miescher and the discovery of DNA.

Over the past 60 years, DNA has risen from being an obscure molecule with presumed accessory or structural functions inside the nucleus to the icon of modern bioscience. The story of DNA often seems to begin in 1944 with Avery, MacLeod, and McCarty showing that DNA is the hereditary material. Within 10 years of their experiments, Watson and Crick deciphered its structure and yet another decade on the genetic code was cracked. However, the DNA story has already begun in 1869, with the young Swiss physician Friedrich Miescher. Having just completed his education as a physician, Miescher moved to Tübingen to work in the laboratory of biochemist Hoppe-Seyler, his aim being to elucidate the building blocks of life. Choosing leucocytes as his source material, he first investigated the proteins in these cells. However, during these experiments, he noticed a substance with unexpected properties that did not match those of proteins. Miescher had obtained the first crude purification of DNA. He further examined the properties and composition of this enigmatic substance and showed that it fundamentally differed from proteins. Due to its occurrence in the cells' nuclei, he termed the novel substance "nuclein"--a term still preserved in today's name deoxyribonucleic acid.

Animals↗

Bootstrapping the lexicon: a computational model of infant speech segmentation.

Prelinguistic infants must find a way to isolate meaningful chunks from the continuous streams of speech that they hear. BootLex, a new model which uses distributional cues to build a lexicon, demonstrates how much can be accomplished using this single source of information. This conceptually simple probabilistic algorithm achieves significant segmentation results on various kinds of language corpora - English, Japanese, and Spanish; child- and adult-directed speech, and written texts; and several variations in coding structure - and reveals which statistical characteristics of the input have an influence on segmentation performance. BootLex is then compared, quantitatively and qualitatively, with three other groups of computational models of the same infant segmentation process, paying particular attention to functional characteristics of the models and their similarity to human cognition. Commonalities and contrasts among the models are discussed, as well as their implications both for theories of the cognitive problem of segmentation itself, and for the general enterprise of computational cognitive modeling.

Algorithms↗

A formal approach to integrating synonyms with a reference terminology.

Medical terminologies continue to grow in scope, completeness and detail. The emerging generation of terminology systems define concepts in terms of their position within a categorical structure. It is still necessary, however, to access and represent the concepts using everyday spoken and written language, which introduces both lexical and semantic ambiguity. This ambiguity can have a negative impact on both selectivity and recall when it comes to associating free-form textual phrases with their coded equivalent. Lexical ambiguity issues can often be addressed algorithmically, but semantic ambiguity presents a more difficult problem. A common solution to the semantic problem is to associate many different representational permutations with a given target concept. This approach has several drawbacks. An alternate solution is to build separate synonym tables that can serve as permuted indices into the terms representing the underlying concepts. A potential shortcoming of this approach, however, is a further reduction in the lookup selectivity. One possible source of loss of selectivity could be "meaning drift"--the gradual change in meaning that can be introduced when following a chain of nearly synonymous words. We posited that organizing synonyms into separate "meaning clusters" might reduce this loss in precision, but the results of this study did not bear that out.

Abstracting and Indexing↗

International Interface Standard for Food Databases.

An International Interface Standard for Food Databases is under development to help overcome the technical and semantic barriers to the use of food-related databases. The Interface Standard is a system for efficient storage of all relevant descriptive information about foods. The schema for the Standard consists of ten components--food/food product identification, food names, LANGUAL factors, other food descriptors, other descriptive coding systems, ingredients/recipes, standards, substances, organizations, and data sources. The Interface allows for retrievals of data associated with specific foods from databases by using queries based on any of a wide variety of descriptive terms. The schema of the Interface has been completed; the remaining work is to build the computer software to provide access to, and use of, the schema.

Computers↗

Building effective community-academic partnerships to improve health: a qualitative study of perspectives from communities.

PURPOSE: To identify, through a qualitative study, community perspectives on the critical factors that facilitate the development, effectiveness, and sustainability of community-academic partnerships. METHOD: Between June 1998 and April 1999, 25 semistructured interviews were conducted with community members who represented eight partnerships at five academic health centers. Content analysis and open coding were performed on the data, and patterns of ideas and concepts were categorized. RESULTS: After review of the data, responses from three partnerships were excluded. Nine major themes that community respondents thought strongly influenced the effectiveness of community-academic partnerships emerged from respondents from the remaining five partnerships: (1) creation and nurturing of trust; (2) respect for a community's knowledge; (3) community-defined and prioritized needs and goals; (4) mutual division of roles and responsibilities; (5) continuous flexibility, compromise, and feedback; (6) strengthening of community capacity; (7) joint and equitable allocation of resources; (8) sustainability and community ownership; and (9) insufficient funding periods. CONCLUSION: The themes that emerged from this study of the perceptions and experiences of the community partners in community-academic partnerships can be critical to further developing and evolving these partnerships.

Academic Medical Centers↗

Analysis of data from spilling experiments performed with liquid hydrogen.

This work describes the modelling of liquid hydrogen release experiments using the ADREA-HF 3-D time dependent finite volume code for cloud dispersion, jointly developed by DEMOKRITOS and JRC-Ispra. The experiments were performed by Batelle Ingenieurtechnik for BAM (Bundesanstalt fur Materialforschung und Prufung), Berlin, in the frame of the Euro-Quebec-Hydro-Hydrogen-Pilot-Project and they mainly deal with LH2 near ground releases between buildings. In the present study, the experimental trial #5 was assumed for simulation due to the fact that in this release the largest number of sensor readings were obtained. The simulations illustrated the complex behaviour of LH2 dispersion in presence of buildings, characterized by complicated wind patterns, plume back flow near the source, dense gas behaviour at near range and significant buoyant behaviour at the far range. The simulations showed the strong effect of ground heating in the LH2 dispersion. The model also revealed major features of the dispersion that had to do with the "dense" behaviour of the cold hydrogen and the buoyant behaviour of the "warming-up" gas as well as the interaction of the building and the release wake. Such a behaviour was in qualitative and even quantitative agreement with the experiment. The results are given in terms of concentration time series, scatter plots, contour plots, wind field vector plots and 3-D concentration wireframes. Given all experiment uncertainties, the model gives reasonable results on concentrations levels.

Accidents↗

Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system.

The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4-2%, MCNP-10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of the drug pharmacokinetics in MTR can only be properly accounted for by image-based, patient-specific treatment planning, as has been common in external beam radiation therapy for many years. MINERVA offers 3D Monte Carlo-based MTR treatment planning as its first integrated operational capability. The new MINERVA system will ultimately incorporate capabilities for a comprehensive list of radiation therapies. In progress are modules for external beam photon-electron therapy and boron neutron capture therapy (BNCT). Brachytherapy and proton therapy are planned. Through the open application programming interface (API), other groups can add their own modules and share them with the community.

Boron Neutron Capture Therapy↗

DNAskew: statistical analysis of base compositional asymmetry and prediction of replication boundaries in the genome sequences.

Sueoka and Lobry declared respectively that, in the absence of bias between the two DNA strands for mutation and selection, the base composition within each strand should be A=T and C=G (this state is called Parity Rule type 2, PR2). However, the genome sequences of many bacteria, vertebrates and viruses showed asymmetries in base composition and gene direction. To determine the relationship of base composition skews with replication orientation, gene function, codon usage biases and phylogenetic evolution, in this paper a program called DNAskew was developed for the statistical analysis of strand asymmetry and codon composition bias in the DNA sequence. In addition, the program can also be used to predict the replication boundaries of genome sequences. The method builds on the fact that there are compositional asymmetries between the leading and the lagging strand for replication. DNAskew was written in Perl script language and implemented on the LINUX operating system. It works quickly with annotated or unannotated sequences in GBFF (GenBank flatfile) or fasta format. The source code is freely available for academic use at http://www.epizooty.com/pub/stat/DNAskew.

Algorithms↗

Dose rate calculations for a reconnaissance vehicle.

A Chemical Nuclear Reconnaissance System (CNRS) has been developed by the British Ministry of Defence to make chemical and radiation measurements on contaminated terrain using appropriate sensors and recording equipment installed in a land rover. A research programme is under way to develop and validate a predictive capability to calculate the build-up of contamination on the vehicle, radiation detector performance and dose rates to the occupants of the vehicle. This paper describes the geometric model of the vehicle and the methodology used for calculations of detector response. Calculated dose rates obtained using the MCBEND Monte Carlo radiation transport computer code in adjoint mode are presented. These address the transient response of the detectors as the vehicle passes through a contaminated area. Calculated dose rates were found to agree with the measured data to be within the experimental uncertainties, thus giving confidence in the shielding model of the vehicle and its application to other scenarios.

Automobiles↗

Oxidative Stress Associated LncRNAs as Potential Biomarkers for Prognosis and Immune Responses in Lung Squamous Cell Carcinoma Patients.

Long-chain non-coding RNA (lncRNA) significantly influences lung squamous cell carcinoma's (LUSC) prognostic value and immune infiltration. This study aimed to demonstrate how oxidative stress-related lncRNAs impact lung squamous cell carcinoma (SCC). The Cancer Genome Atlas (TCGA) dataset gathered transcriptome information and related clinical data for LUSC. To build a prognostic model, 10 prognostic-related genes were identified using a series of bioinformatics analyses that compared the OS gene's aberrant expression in tumor and healthy tissues, as well as its association with malignancy. Subjects were stratified into high- and low-risk groups based on the median risk score derived from the 10-gene signature. While the mathematical risk model demonstrated limited independent predictive performance in the validation cohort (AUC ~ 0.5), functional and immunological evaluations revealed significant differences in the tumor microenvironment (TME) across risk strata. Specifically, high-risk patients exhibited distinct immune infiltration profiles and altered immunological scores relative to their low-risk counterparts. Therefore, rather than serving as a direct clinical prediction tool, this oxidative stress-related lncRNA signature provides valuable biological insights into the immune landscape of LUSC and highlights potential therapeutic targets for further mechanistic investigation.

Humans↗

Risk factors for injuries due to the 1990 earthquake in Luzon, Philippines.

On 16 July 1990, an earthquake measuring 7.7 on the Richter scale struck the island of Luzon, Philippines. A case-control study was carried out to identify the risk factors for earthquake-related injuries and at the same time observations were made on the rescue efforts. Being hit by falling objects was the leading cause of injury (34%). Those injured during the tremor were more likely to have been inside buildings constructed of concrete or mixed materials (odds ratio, 2.6; 95% confidence interval (CI), 1.7-4.1) and to have been on the middle floors of multistorey buildings (odds ratio, 3.4; 95% CI, 2.2-5.5). Leaving a building during the earthquake was a protective behaviour (odds ratio, 0.3; 95% CI, 0.2-0.8). Of the 235 survivors who were trapped and rescued alive from the rubble, 99% were rescued within 48 hours of the impact of the tremor. These findings should prove useful in developing seismic safety codes. People should be taught proper evasive actions to take during earthquakes, and training in basic first aid and methods of rescue should be an integral part of community preparedness programmes.

Case-Control Studies↗

Standards to support development of terminological systems for healthcare telematics.

The Technical Committee on "Medical Informatics" of the European Committee for Standardization (CEN/TC251) is supporting developers of terminological systems in healthcare by a series of standards. The dream of "universal" coding system was abandoned in favor of a coherent family of terminologies, diversified according to tasks; two ideas were introduced: (1) the "categorical structure", i.e. a model of semantic categories and their relations within a subject field and (2) the "cross-thesaurus", i.e. a system of descriptors to build a systematic representation (called here "dissection") for each terminological phrase, coherent across diverse terminologies on a given subject field. The goal is to assure coexistence and interoperability (and reciprocal support for development and maintenance) to three generations of systems: (1) traditional paper-based systems (first generation); (2) compositional systems built according to a categorical structure and a cross-thesaurus (second generation) and (3) formal models (third generation). Various scenarios are presented, on the exploitation of computer-based terminological systems. The idea of "operational meaning" of terminological phrases within administrative and organizational contexts and the idea of "task-oriented details" are also introduced, to justify and exploit design constraints on terminological systems.

Europe↗

A numerical simulation method and analysis of a complete thermoacoustic-Stirling engine.

Thermoacoustic prime movers can generate pressure oscillation without any moving parts on self-excited thermoacoustic effect. The details of the numerical simulation methodology for thermoacoustic engines are presented in the paper. First, a four-port network method is used to build the transcendental equation of complex frequency as a criterion to judge if temperature distribution of the whole thermoacoustic system is correct for the case with given heating power. Then, the numerical simulation of a thermoacoustic-Stirling heat engine is carried out. It is proved that the numerical simulation code can run robustly and output what one is interested in. Finally, the calculated results are compared with the experiments of the thermoacoustic-Stirling heat engine (TASHE). It shows that the numerical simulation can agrees with the experimental results with acceptable accuracy.

Journal Article↗

Will you be there for me when things go right? Supportive responses to positive event disclosures.

Close relationship partners often share successes and triumphs with one another, but this experience is rarely the focus of empirical study. In this study, 79 dating couples completed measures of relationship well-being and then participated in videotaped interactions in which they took turns discussing recent positive and negative events. Disclosers rated how understood, validated, and cared for they felt in each discussion, and outside observers coded responders' behavior. Both self-report data and observational codes showed that 2 months later, responses to positive event discussions were more closely related to relationship well-being and break-up than were responses to negative event discussions. The results are discussed in terms of the recurrent, but often overlooked, role that positive emotional exchanges play in building relationship resources.

Adult↗

A phylogenomic approach to bacterial phylogeny: evidence of a core of genes sharing a common history.

It has been claimed that complete genome sequences would clarify phylogenetic relationships between organisms, but up to now, no satisfying approach has been proposed to use efficiently these data. For instance, if the coding of presence or absence of genes in complete genomes gives interesting results, it does not take into account the phylogenetic information contained in sequences and ignores hidden paralogies by using a BLAST reciprocal best hit definition of orthology. In addition, concatenation of sequences of different genes as well as building of consensus trees only consider the few genes that are shared among all organisms. Here we present an attempt to use a supertree method to build the phylogenetic tree of 45 organisms, with special focus on bacterial phylogeny. This led us to perform a phylogenetic study of congruence of tree topologies, which allows the identification of a core of genes supporting similar species phylogeny. We then used this core of genes to infer a tree. This phylogeny presents several differences with the rRNA phylogeny, notably for the position of hyperthermophilic bacteria.

Computational Biology↗