Principles of protein targeting to the nucleolus.

Science.gov (United States)

Martin, Robert M; Ter-Avetisyan, Gohar; Herce, Henry D; Ludwig, Anne K; Lättig-Tünnemann, Gisela; Cardoso, M Cristina

2015-01-01

The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of rRNA synthesis and assembly of ribosomes. Nucleolar proteins dynamically localize and accumulate in this nuclear compartment relative to the surrounding nucleoplasm. In this study, we have assessed the molecular requirements that are necessary and sufficient for the localization and accumulation of peptides and proteins inside the nucleoli of living cells. The data showed that positively charged peptide entities composed of arginines alone and with an isoelectric point at and above 12.6 are necessary and sufficient for mediating significant nucleolar accumulation. A threshold of 6 arginines is necessary for peptides to accumulate in nucleoli, but already 4 arginines are sufficient when fused within 15 amino acid residues of a nuclear localization signal of a protein. Using a pH sensitive dye, we found that the nucleolar compartment is particularly acidic when compared to the surrounding nucleoplasm and, hence, provides the ideal electrochemical environment to bind poly-arginine containing proteins. In fact, we found that oligo-arginine peptides and GFP fusions bind RNA in vitro. Consistent with RNA being the main binding partner for arginines in the nucleolus, we found that the same principles apply to cells from insects to man, indicating that this mechanism is highly conserved throughout evolution.

Working with Proteins in silico: A Review of Online Available Tools for Basic Identification of Proteins

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Caner Yavuz

2017-01-01

Full Text Available Increase in online available bioinformatics tools for protein research creates an important opportunity for scientists to reveal characteristics of the protein of interest by only starting from the predicted or known amino acid sequence without fully depending on experimental approaches. There are many sophisticated tools used for diverse purposes; however, there are not enough reviews covering the tips and tricks in selecting and using the correct tools as the literature mainly state the promotion of the new ones. In this review, with the aim of providing young scientists with no specific experience on protein work a reliable starting point for in silico analysis of the protein of interest, we summarized tools for annotation, identification of motifs and domains, determination isoelectric point, molecular weight, subcellular localization, and post-translational modifications by focusing on the important points to be considered while selecting from online available tools.

Principles of assembly reveal a periodic table of protein complexes.

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Ahnert, Sebastian E; Marsh, Joseph A; Hernández, Helena; Robinson, Carol V; Teichmann, Sarah A

2015-12-11

Structural insights into protein complexes have had a broad impact on our understanding of biological function and evolution. In this work, we sought a comprehensive understanding of the general principles underlying quaternary structure organization in protein complexes. We first examined the fundamental steps by which protein complexes can assemble, using experimental and structure-based characterization of assembly pathways. Most assembly transitions can be classified into three basic types, which can then be used to exhaustively enumerate a large set of possible quaternary structure topologies. These topologies, which include the vast majority of observed protein complex structures, enable a natural organization of protein complexes into a periodic table. On the basis of this table, we can accurately predict the expected frequencies of quaternary structure topologies, including those not yet observed. These results have important implications for quaternary structure prediction, modeling, and engineering. Copyright © 2015, American Association for the Advancement of Science.

PPI finder: a mining tool for human protein-protein interactions.

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Min He

Full Text Available BACKGROUND: The exponential increase of published biomedical literature prompts the use of text mining tools to manage the information overload automatically. One of the most common applications is to mine protein-protein interactions (PPIs from PubMed abstracts. Currently, most tools in mining PPIs from literature are using co-occurrence-based approaches or rule-based approaches. Hybrid methods (frame-based approaches by combining these two methods may have better performance in predicting PPIs. However, the predicted PPIs from these methods are rarely evaluated by known PPI databases and co-occurred terms in Gene Ontology (GO database. METHODOLOGY/PRINCIPAL FINDINGS: We here developed a web-based tool, PPI Finder, to mine human PPIs from PubMed abstracts based on their co-occurrences and interaction words, followed by evidences in human PPI databases and shared terms in GO database. Only 28% of the co-occurred pairs in PubMed abstracts appeared in any of the commonly used human PPI databases (HPRD, BioGRID and BIND. On the other hand, of the known PPIs in HPRD, 69% showed co-occurrences in the literature, and 65% shared GO terms. CONCLUSIONS: PPI Finder provides a useful tool for biologists to uncover potential novel PPIs. It is freely accessible at http://liweilab.genetics.ac.cn/tm/.

Principles for designing proteins with cavities formed by curved β sheets

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Marcos, Enrique; Basanta, Benjamin; Chidyausiku, Tamuka M.; Tang, Yuefeng; Oberdorfer, Gustav; Liu, Gaohua; Swapna, G. V. T.; Guan, Rongjin; Silva, Daniel-Adriano; Dou, Jiayi; Pereira, Jose Henrique; Xiao, Rong; Sankaran, Banumathi; Zwart, Peter H.; Montelione, Gaetano T.; Baker, David

2017-01-12

Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-sheet curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites.

Twister Protein: a ludic tool involving protein synthesis

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Aline Weyh

2015-07-01

Full Text Available Several studies show that students of various grade levels report the Genetics as an abstract theme and difficult to assimilate by the students, with multiple problems in the teaching-learning process and becoming necessary the development of auxiliary practices. Among the teaching tools, the game is the most currently opted playful activity by stimulating multiple intelligences, allowing greater student-teacher interaction. This work seeks the production of an innovative and dynamic educational game, Twister Protein, as a pedagogical resource for Genetics discipline. The development of the game was based on the use of easily accessible and low cost materials by teachers, allowing the knowledge of transcription, translation and protein folding. The activity was proposed and applied in the classroom with pilot undergraduate students. The fun associated with the knowledge of science not only allowed a better memorization of the content addressed, as aroused the curiosity, theme reflection, character building and collaborative spirits, as well as competitiveness through the interaction between class. This practice proved to be an effective tool in the escape from routine and fault repair of the theoretical process.

Organizing principles as tools for bridging the gap between system theory and biological experimentation.

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Mekios, Constantinos

2016-04-01

Twentieth-century theoretical efforts towards the articulation of general system properties came short of having the significant impact on biological practice that their proponents envisioned. Although the latter did arrive at preliminary mathematical formulations of such properties, they had little success in showing how these could be productively incorporated into the research agenda of biologists. Consequently, the gap that kept system-theoretic principles cut-off from biological experimentation persisted. More recently, however, simple theoretical tools have proved readily applicable within the context of systems biology. In particular, examples reviewed in this paper suggest that rigorous mathematical expressions of design principles, imported primarily from engineering, could produce experimentally confirmable predictions of the regulatory properties of small biological networks. But this is not enough for contemporary systems biologists who adopt the holistic aspirations of early systemologists, seeking high-level organizing principles that could provide insights into problems of biological complexity at the whole-system level. While the presented evidence is not conclusive about whether this strategy could lead to the realization of the lofty goal of a comprehensive explanatory integration, it suggests that the ongoing quest for organizing principles is pragmatically advantageous for systems biologists. The formalisms postulated in the course of this process can serve as bridges between system-theoretic concepts and the results of molecular experimentation: they constitute theoretical tools for generalizing molecular data, thus producing increasingly accurate explanations of system-wide phenomena.

Leverage principle of retardation signal in titration of double protein via chip moving reaction boundary electrophoresis.

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Zhang, Liu-Xia; Cao, Yi-Ren; Xiao, Hua; Liu, Xiao-Ping; Liu, Shao-Rong; Meng, Qing-Hua; Fan, Liu-Yin; Cao, Cheng-Xi

2016-03-15

In the present work we address a simple, rapid and quantitative analytical method for detection of different proteins present in biological samples. For this, we proposed the model of titration of double protein (TDP) and its relevant leverage theory relied on the retardation signal of chip moving reaction boundary electrophoresis (MRBE). The leverage principle showed that the product of the first protein content and its absolute retardation signal is equal to that of the second protein content and its absolute one. To manifest the model, we achieved theoretical self-evidence for the demonstration of the leverage principle at first. Then relevant experiments were conducted on the TDP-MRBE chip. The results revealed that (i) there was a leverage principle of retardation signal within the TDP of two pure proteins, and (ii) a lever also existed within these two complex protein samples, evidently demonstrating the validity of TDP model and leverage theory in MRBE chip. It was also showed that the proposed technique could provide a rapid and simple quantitative analysis of two protein samples in a mixture. Finally, we successfully applied the developed technique for the quantification of soymilk in adulterated infant formula. The TDP-MRBE opens up a new window for the detection of adulteration ratio of the poor food (milk) in blended high quality one. Copyright © 2015 Elsevier B.V. All rights reserved.

Gene Unprediction with Spurio: A tool to identify spurious protein sequences.

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Höps, Wolfram; Jeffryes, Matt; Bateman, Alex

2018-01-01

We now have access to the sequences of tens of millions of proteins. These protein sequences are essential for modern molecular biology and computational biology. The vast majority of protein sequences are derived from gene prediction tools and have no experimental supporting evidence for their translation.  Despite the increasing accuracy of gene prediction tools there likely exists a large number of spurious protein predictions in the sequence databases.  We have developed the Spurio tool to help identify spurious protein predictions in prokaryotes.  Spurio searches the query protein sequence against a prokaryotic nucleotide database using tblastn and identifies homologous sequences. The tblastn matches are used to score the query sequence's likelihood of being a spurious protein prediction using a Gaussian process model. The most informative feature is the appearance of stop codons within the presumed translation of homologous DNA sequences. Benchmarking shows that the Spurio tool is able to distinguish spurious from true proteins. However, transposon proteins are prone to be predicted as spurious because of the frequency of degraded homologs found in the DNA sequence databases. Our initial experiments suggest that less than 1% of the proteins in the UniProtKB sequence database are likely to be spurious and that Spurio is able to identify over 60 times more spurious proteins than the AntiFam resource. The Spurio software and source code is available under an MIT license at the following URL: https://bitbucket.org/bateman-group/spurio.

SafetyBarrierManager, a software tool to perform risk analysis using ARAMIS's principles

DEFF Research Database (Denmark)

Duijm, Nijs Jan

2017-01-01

of the ARAMIS project, Risø National Laboratory started developing a tool that could implement these methodologies, leading to SafetyBarrierManager. The tool is based on the principles of “safety‐barrier diagrams”, which are very similar to “bowties”, with the possibility of performing quantitative analysis......The ARAMIS project resulted in a number of methodologies, dealing with among others: the development of standard fault trees and “bowties”; the identification and classification of safety barriers; and including the quality of safety management into the quantified risk assessment. After conclusion....... The tool allows constructing comprehensive fault trees, event trees and safety‐barrier diagrams. The tool implements the ARAMIS idea of a set of safety barrier types, to which a number of safety management issues can be linked. By rating the quality of these management issues, the operational probability...

A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.

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Agrawal, Neeraj J; Helk, Bernhard; Trout, Bernhardt L

2014-01-21

Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Synthetic RNAs for Gene Regulation: Design Principles and Computational Tools

International Nuclear Information System (INIS)

Laganà, Alessandro; Shasha, Dennis; Croce, Carlo Maria

2014-01-01

The use of synthetic non-coding RNAs for post-transcriptional regulation of gene expression has not only become a standard laboratory tool for gene functional studies but it has also opened up new perspectives in the design of new and potentially promising therapeutic strategies. Bioinformatics has provided researchers with a variety of tools for the design, the analysis, and the evaluation of RNAi agents such as small-interfering RNA (siRNA), short-hairpin RNA (shRNA), artificial microRNA (a-miR), and microRNA sponges. More recently, a new system for genome engineering based on the bacterial CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats), was shown to have the potential to also regulate gene expression at both transcriptional and post-transcriptional level in a more specific way. In this mini review, we present RNAi and CRISPRi design principles and discuss the advantages and limitations of the current design approaches.

Synthetic RNAs for Gene Regulation: Design Principles and Computational Tools

Energy Technology Data Exchange (ETDEWEB)

Laganà, Alessandro [Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (United States); Shasha, Dennis [Courant Institute of Mathematical Sciences, New York University, New York, NY (United States); Croce, Carlo Maria [Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH (United States)

2014-12-11

The use of synthetic non-coding RNAs for post-transcriptional regulation of gene expression has not only become a standard laboratory tool for gene functional studies but it has also opened up new perspectives in the design of new and potentially promising therapeutic strategies. Bioinformatics has provided researchers with a variety of tools for the design, the analysis, and the evaluation of RNAi agents such as small-interfering RNA (siRNA), short-hairpin RNA (shRNA), artificial microRNA (a-miR), and microRNA sponges. More recently, a new system for genome engineering based on the bacterial CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats), was shown to have the potential to also regulate gene expression at both transcriptional and post-transcriptional level in a more specific way. In this mini review, we present RNAi and CRISPRi design principles and discuss the advantages and limitations of the current design approaches.

PAnalyzer: A software tool for protein inference in shotgun proteomics

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Prieto Gorka

2012-11-01

Full Text Available Abstract Background Protein inference from peptide identifications in shotgun proteomics must deal with ambiguities that arise due to the presence of peptides shared between different proteins, which is common in higher eukaryotes. Recently data independent acquisition (DIA approaches have emerged as an alternative to the traditional data dependent acquisition (DDA in shotgun proteomics experiments. MSE is the term used to name one of the DIA approaches used in QTOF instruments. MSE data require specialized software to process acquired spectra and to perform peptide and protein identifications. However the software available at the moment does not group the identified proteins in a transparent way by taking into account peptide evidence categories. Furthermore the inspection, comparison and report of the obtained results require tedious manual intervention. Here we report a software tool to address these limitations for MSE data. Results In this paper we present PAnalyzer, a software tool focused on the protein inference process of shotgun proteomics. Our approach considers all the identified proteins and groups them when necessary indicating their confidence using different evidence categories. PAnalyzer can read protein identification files in the XML output format of the ProteinLynx Global Server (PLGS software provided by Waters Corporation for their MSE data, and also in the mzIdentML format recently standardized by HUPO-PSI. Multiple files can also be read simultaneously and are considered as technical replicates. Results are saved to CSV, HTML and mzIdentML (in the case of a single mzIdentML input file files. An MSE analysis of a real sample is presented to compare the results of PAnalyzer and ProteinLynx Global Server. Conclusions We present a software tool to deal with the ambiguities that arise in the protein inference process. Key contributions are support for MSE data analysis by ProteinLynx Global Server and technical replicates

Tools for controlling protein interactions with light

Science.gov (United States)

Tucker, Chandra L.; Vrana, Justin D.; Kennedy, Matthew J.

2014-01-01

Genetically-encoded actuators that allow control of protein-protein interactions with light, termed ‘optical dimerizers’, are emerging as new tools for experimental biology. In recent years, numerous new and versatile dimerizer systems have been developed. Here we discuss the design of optical dimerizer experiments, including choice of a dimerizer system, photoexcitation sources, and coordinate use of imaging reporters. We provide detailed protocols for experiments using two dimerization systems we previously developed, CRY2/CIB and UVR8/UVR8, for use controlling transcription, protein localization, and protein secretion with light. Additionally, we provide instructions and software for constructing a pulse-controlled LED light device for use in experiments requiring extended light treatments. PMID:25181301

Automatic generation of bioinformatics tools for predicting protein-ligand binding sites.

Science.gov (United States)

Komiyama, Yusuke; Banno, Masaki; Ueki, Kokoro; Saad, Gul; Shimizu, Kentaro

2016-03-15

Predictive tools that model protein-ligand binding on demand are needed to promote ligand research in an innovative drug-design environment. However, it takes considerable time and effort to develop predictive tools that can be applied to individual ligands. An automated production pipeline that can rapidly and efficiently develop user-friendly protein-ligand binding predictive tools would be useful. We developed a system for automatically generating protein-ligand binding predictions. Implementation of this system in a pipeline of Semantic Web technique-based web tools will allow users to specify a ligand and receive the tool within 0.5-1 day. We demonstrated high prediction accuracy for three machine learning algorithms and eight ligands. The source code and web application are freely available for download at http://utprot.net They are implemented in Python and supported on Linux. shimizu@bi.a.u-tokyo.ac.jp Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Acute-phase proteins: As diagnostic tool

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Sachin Jain

2011-01-01

Full Text Available The varied reactions of the host to infection, inflammation, or trauma are collectively known as the acute-phase response and encompass a wide range of pathophysiological responses such as pyrexia, leukocytosis, hormone alterations, and muscle protein depletion combining to minimize tissue damage while enhancing the repair process. The mechanism for stimulation of hepatic production of acute-phase proteins is by proinflammatory cytokines. The functions of positive acute-phase proteins (APP are regarded as important in optimization and trapping of microorganism and their products, in activating the complement system, in binding cellular remnants like nuclear fractions, in neutralizing enzymes, scavenging free hemoglobin and radicals, and in modulating the host′s immune response. APP can be used as diagnostic tool in many diseases like bovine respiratory syncytial virus, prostate cancer, bronchopneumonia, multiple myeloma, mastitis, Streptococcus suis infection, starvation, or lymphatic neoplasia. Thus, acute-phase proteins may provide an alternative means of monitoring animal health.

Mobility analysis tool based on the fundamental principle of conservation of energy.

Energy Technology Data Exchange (ETDEWEB)

Spletzer, Barry Louis; Nho, Hyuchul C.; Salton, Jonathan Robert

2007-08-01

In the past decade, a great deal of effort has been focused in research and development of versatile robotic ground vehicles without understanding their performance in a particular operating environment. As the usage of robotic ground vehicles for intelligence applications increases, understanding mobility of the vehicles becomes critical to increase the probability of their successful operations. This paper describes a framework based on conservation of energy to predict the maximum mobility of robotic ground vehicles over general terrain. The basis of the prediction is the difference between traction capability and energy loss at the vehicle-terrain interface. The mission success of a robotic ground vehicle is primarily a function of mobility. Mobility of a vehicle is defined as the overall capability of a vehicle to move from place to place while retaining its ability to perform its primary mission. A mobility analysis tool based on the fundamental principle of conservation of energy is described in this document. The tool is a graphical user interface application. The mobility analysis tool has been developed at Sandia National Laboratories, Albuquerque, NM. The tool is at an initial stage of development. In the future, the tool will be expanded to include all vehicles and terrain types.

Tools for predicting the PK/PD of therapeutic proteins.

Science.gov (United States)

Diao, Lei; Meibohm, Bernd

2015-07-01

Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. In this review, the authors discuss tools that are utilized to describe and predict the PK/PD features of therapeutic proteins and that are valuable additions in the armamentarium of drug development approaches to facilitate and accelerate their successful preclinical and clinical development. A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.

Caged Protein Prenyltransferase Substrates: Tools for Understanding Protein Prenylation

Energy Technology Data Exchange (ETDEWEB)

DeGraw, Amanda J.; Hast, Michael A.; Xu, Juhua; Mullen, Daniel; Beese, Lorena S.; Barany, George; Distefano, Mark D. (Duke); (UMM)

2010-11-15

Originally designed to block the prenylation of oncogenic Ras, inhibitors of protein farnesyltransferase currently in preclinical and clinical trials are showing efficacy in cancers with normal Ras. Blocking protein prenylation has also shown promise in the treatment of malaria, Chagas disease and progeria syndrome. A better understanding of the mechanism, targets and in vivo consequences of protein prenylation are needed to elucidate the mode of action of current PFTase (Protein Farnesyltransferase) inhibitors and to create more potent and selective compounds. Caged enzyme substrates are useful tools for understanding enzyme mechanism and biological function. Reported here is the synthesis and characterization of caged substrates of PFTase. The caged isoprenoid diphosphates are poor substrates prior to photolysis. The caged CAAX peptide is a true catalytically caged substrate of PFTase in that it is to not a substrate, yet is able to bind to the enzyme as established by inhibition studies and X-ray crystallography. Irradiation of the caged molecules with 350 nm light readily releases their cognate substrate and their photolysis products are benign. These properties highlight the utility of those analogs towards a variety of in vitro and in vivo applications.

SitesIdentify: a protein functional site prediction tool

Directory of Open Access Journals (Sweden)

Doig Andrew J

2009-11-01

Full Text Available Abstract Background The rate of protein structures being deposited in the Protein Data Bank surpasses the capacity to experimentally characterise them and therefore computational methods to analyse these structures have become increasingly important. Identifying the region of the protein most likely to be involved in function is useful in order to gain information about its potential role. There are many available approaches to predict functional site, but many are not made available via a publicly-accessible application. Results Here we present a functional site prediction tool (SitesIdentify, based on combining sequence conservation information with geometry-based cleft identification, that is freely available via a web-server. We have shown that SitesIdentify compares favourably to other functional site prediction tools in a comparison of seven methods on a non-redundant set of 237 enzymes with annotated active sites. Conclusion SitesIdentify is able to produce comparable accuracy in predicting functional sites to its closest available counterpart, but in addition achieves improved accuracy for proteins with few characterised homologues. SitesIdentify is available via a webserver at http://www.manchester.ac.uk/bioinformatics/sitesidentify/

Extremum principles for irreversible processes

International Nuclear Information System (INIS)

Hillert, M.; Agren, J.

2006-01-01

Hamilton's extremum principle is a powerful mathematical tool in classical mechanics. Onsager's extremum principle may play a similar role in irreversible thermodynamics and may also become a valuable tool. His principle may formally be regarded as a principle of maximum rate of entropy production but does not have a clear physical interpretation. Prigogine's principle of minimum rate of entropy production has a physical interpretation when it applies, but is not strictly valid except for a very special case

Specific Proteins in Nontuberculous Mycobacteria: New Potential Tools

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Patricia Orduña

2015-01-01

Full Text Available Nontuberculous mycobacteria (NTM have been isolated from water, soil, air, food, protozoa, plants, animals, and humans. Although most NTM are saprophytes, approximately one-third of NTM have been associated with human diseases. In this study, we did a comparative proteomic analysis among five NTM strains isolated from several sources. There were different numbers of protein spots from M. gordonae (1,264, M. nonchromogenicum type I (894, M. nonchromogenicum type II (935, M. peregrinum (806, and M. scrofulaceum/Mycobacterium mantenii (1,486 strains, respectively. We identified 141 proteins common to all strains and specific proteins to each NTM strain. A total of 23 proteins were selected for its identification. Two of the common proteins identified (short-chain dehydrogenase/reductase SDR and diguanylate cyclase did not align with M. tuberculosis complex protein sequences, which suggest that these proteins are found only in the NTM strains. Some of the proteins identified as common to all strains can be used as markers of NTM exposure and for the development of new diagnostic tools. Additionally, the specific proteins to NTM strains identified may represent potential candidates for the diagnosis of diseases caused by these mycobacteria.

PRmePRed: A protein arginine methylation prediction tool.

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Pawan Kumar

Full Text Available Protein methylation is an important Post-Translational Modification (PTMs of proteins. Arginine methylation carries out and regulates several important biological functions, including gene regulation and signal transduction. Experimental identification of arginine methylation site is a daunting task as it is costly as well as time and labour intensive. Hence reliable prediction tools play an important task in rapid screening and identification of possible methylation sites in proteomes. Our preliminary assessment using the available prediction methods on collected data yielded unimpressive results. This motivated us to perform a comprehensive data analysis and appraisal of features relevant in the context of biological significance, that led to the development of a prediction tool PRmePRed with better performance. The PRmePRed perform reasonably well with an accuracy of 84.10%, 82.38% sensitivity, 83.77% specificity, and Matthew's correlation coefficient of 66.20% in 10-fold cross-validation. PRmePRed is freely available at http://bioinfo.icgeb.res.in/PRmePRed/.

NASCENT: an automatic protein interaction network generation tool for non-model organisms.

Science.gov (United States)

Banky, Daniel; Ordog, Rafael; Grolmusz, Vince

2009-04-24

Large quantity of reliable protein interaction data are available for model organisms in public depositories (e.g., MINT, DIP, HPRD, INTERACT). Most data correspond to experiments with the proteins of Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Caenorhabditis elegans, Escherichia coli and Mus musculus. For other important organisms the data availability is poor or non-existent. Here we present NASCENT, a completely automatic web-based tool and also a downloadable Java program, capable of modeling and generating protein interaction networks even for non-model organisms. The tool performs protein interaction network modeling through gene-name mapping, and outputs the resulting network in graphical form and also in computer-readable graph-forms, directly applicable by popular network modeling software. http://nascent.pitgroup.org.

First principles studies of electron tunneling in proteins

Science.gov (United States)

Hayashi, Tomoyuki; Stuchebrukhov, Alexei A.

2014-01-01

A first principles study of electronic tunneling along the chain of seven Fe/S clusters in respiratory complex I, a key enzyme in the respiratory electron transport chain, is described. The broken-symmetry states of the Fe/S metal clusters calculated at both DFT and semi-empirical ZINDO levels were utilized to examine both the extremely weak electronic couplings between Fe/S clusters and the tunneling pathways, which provide a detailed atomistic-level description of the charge transfer process in the protein. One-electron tunneling approximation was found to hold within a reasonable accuracy, with only a moderate induced polarization of the core electrons. The method is demonstrated to be able to calculate accurately the coupling matrix elements as small as 10−4 cm−1. A distinct signature of the wave properties of electrons is observed as quantum interferences of multiple tunneling pathways. PMID:25383312

ProBiS tools (algorithm, database, and web servers) for predicting and modeling of biologically interesting proteins.

Science.gov (United States)

Konc, Janez; Janežič, Dušanka

2017-09-01

ProBiS (Protein Binding Sites) Tools consist of algorithm, database, and web servers for prediction of binding sites and protein ligands based on the detection of structurally similar binding sites in the Protein Data Bank. In this article, we review the operations that ProBiS Tools perform, provide comments on the evolution of the tools, and give some implementation details. We review some of its applications to biologically interesting proteins. ProBiS Tools are freely available at http://probis.cmm.ki.si and http://probis.nih.gov. Copyright © 2017 Elsevier Ltd. All rights reserved.

A tool for calculating binding-site residues on proteins from PDB structures

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Hu Jing

2009-08-01

Full Text Available Abstract Background In the research on protein functional sites, researchers often need to identify binding-site residues on a protein. A commonly used strategy is to find a complex structure from the Protein Data Bank (PDB that consists of the protein of interest and its interacting partner(s and calculate binding-site residues based on the complex structure. However, since a protein may participate in multiple interactions, the binding-site residues calculated based on one complex structure usually do not reveal all binding sites on a protein. Thus, this requires researchers to find all PDB complexes that contain the protein of interest and combine the binding-site information gleaned from them. This process is very time-consuming. Especially, combing binding-site information obtained from different PDB structures requires tedious work to align protein sequences. The process becomes overwhelmingly difficult when researchers have a large set of proteins to analyze, which is usually the case in practice. Results In this study, we have developed a tool for calculating binding-site residues on proteins, TCBRP http://yanbioinformatics.cs.usu.edu:8080/ppbindingsubmit. For an input protein, TCBRP can quickly find all binding-site residues on the protein by automatically combining the information obtained from all PDB structures that consist of the protein of interest. Additionally, TCBRP presents the binding-site residues in different categories according to the interaction type. TCBRP also allows researchers to set the definition of binding-site residues. Conclusion The developed tool is very useful for the research on protein binding site analysis and prediction.

Adding biological meaning to human protein-protein interactions identified by yeast two-hybrid screenings: A guide through bioinformatics tools.

Science.gov (United States)

Felgueiras, Juliana; Silva, Joana Vieira; Fardilha, Margarida

2018-01-16

"A man is known by the company he keeps" is a popular expression that perfectly fits proteins. A common approach to characterize the function of a target protein is to identify its interacting partners and thus infer its roles based on the known functions of the interactors. Protein-protein interaction networks (PPINs) have been created for several organisms, including humans, primarily as results of high-throughput screenings, such as yeast two-hybrid (Y2H). Their unequivocal use to understand events underlying human pathophysiology is promising in identifying genes and proteins associated with diseases. Therefore, numerous opportunities have emerged for PPINs as tools for clinical management of diseases: network-based disease classification systems, discovery of biomarkers and identification of therapeutic targets. Despite the great advantages of PPINs, their use is still unrecognised by several researchers who generate high-throughput data to generally characterize interactions in a certain model or to select an interaction to study in detail. We strongly believe that both approaches are not exclusive and that we can use PPINs as a complementary methodology and rich-source of information to the initial study proposal. Here, we suggest a pipeline to deal with Y2H results using bioinformatics tools freely available for academics. Yeast two-hybrid is widely-used to identify protein-protein interactions. Conventionally, the positive clones that result from a yeast two-hybrid screening are sequenced to identify the interactors of the protein of interest (also known as bait protein), and few interactions, thought as potentially relevant for the model in study, are selected for further validation using biochemical methods (e.g. co-immunoprecipitation and co-localization). The huge amount of data that is potentially lost during this conservative approach motivated us to write this tutorial-like review, so that researchers feel encouraged to take advantage of

The APEX Quantitative Proteomics Tool: Generating protein quantitation estimates from LC-MS/MS proteomics results

Directory of Open Access Journals (Sweden)

Saeed Alexander I

2008-12-01

Full Text Available Abstract Background Mass spectrometry (MS based label-free protein quantitation has mainly focused on analysis of ion peak heights and peptide spectral counts. Most analyses of tandem mass spectrometry (MS/MS data begin with an enzymatic digestion of a complex protein mixture to generate smaller peptides that can be separated and identified by an MS/MS instrument. Peptide spectral counting techniques attempt to quantify protein abundance by counting the number of detected tryptic peptides and their corresponding MS spectra. However, spectral counting is confounded by the fact that peptide physicochemical properties severely affect MS detection resulting in each peptide having a different detection probability. Lu et al. (2007 described a modified spectral counting technique, Absolute Protein Expression (APEX, which improves on basic spectral counting methods by including a correction factor for each protein (called Oi value that accounts for variable peptide detection by MS techniques. The technique uses machine learning classification to derive peptide detection probabilities that are used to predict the number of tryptic peptides expected to be detected for one molecule of a particular protein (Oi. This predicted spectral count is compared to the protein's observed MS total spectral count during APEX computation of protein abundances. Results The APEX Quantitative Proteomics Tool, introduced here, is a free open source Java application that supports the APEX protein quantitation technique. The APEX tool uses data from standard tandem mass spectrometry proteomics experiments and provides computational support for APEX protein abundance quantitation through a set of graphical user interfaces that partition thparameter controls for the various processing tasks. The tool also provides a Z-score analysis for identification of significant differential protein expression, a utility to assess APEX classifier performance via cross validation, and a

Developing Nanodiscs as a Tool for Low Resolution Studies of Membrane Proteins

DEFF Research Database (Denmark)

Skar-Gislinge, Nicholas

studies of membrane proteins. So far most of the studies using nanodiscs have been concerning the function of the incorporated membrane protein. However, due to the good control of the size and lipid composition of the nanodisc system, they seem an ideal tool for expanding the use of small angle......Phospholipid nanodiscs are ⇠ 10 nm disc shaped particles consisting of about 150 phospholipids arranged in a central bilayer stabilized by two amphipathic protein ”belts” that wrap around the rim of the bilayer. Because they contain a small bilayer leaflet they can be used as a tool for solution......-assembly process in general, and in particular in relation to incorporation of membrane proteins. This was the aim of work done early in this thesis. Here a detailed model for the small angle x-ray and neutron scattering from the empty nanodisc system was derived and used to describe the nanodisc system with great...

Dielectric properties of proteins from simulations: tools and techniques

Science.gov (United States)

Simonson, Thomas; Perahia, David

1995-09-01

Tools and techniques to analyze the dielectric properties of proteins are described. Microscopic dielectric properties are determined by a susceptibility tensor of order 3 n, where n is the number of protein atoms. For perturbing charges not too close to the protein, the dielectric relaxation free energy is directly related to the dipole-dipole correlation matrix of the unperturbed protein, or equivalently to the covariance matrix of its atomic displacements. These are straightforward to obtain from existing molecular dynamics packages such as CHARMM or X- PLOR. Macroscopic dielectric properties can be derived from the dipolar fluctuations of the protein, by idealizing the protein as one or more spherical media. The dipolar fluctuations are again directly related to the covariance matrix of the atomic displacements. An interesting consequence is that the quasiharmonic approximation, which by definition exactly reproduces this covariance matrix, gives the protein dielectric constant exactly. Finally a technique is reviewed to obtain normal or quasinormal modes of vibration of symmetric protein assemblies. Using elementary group theory, and eliminating the high-frequency modes of vibration of each monomer, the limiting step in terms of memory and computation is finding the normal modes of a single monomer, with the other monomers held fixed. This technique was used to study the dielectric properties of the Tobacco Mosaic Virus protein disk.

AllerTool: a web server for predicting allergenicity and allergic cross-reactivity in proteins.

Science.gov (United States)

Zhang, Zong Hong; Koh, Judice L Y; Zhang, Guang Lan; Choo, Khar Heng; Tammi, Martti T; Tong, Joo Chuan

2007-02-15

Assessment of potential allergenicity and patterns of cross-reactivity is necessary whenever novel proteins are introduced into human food chain. Current bioinformatic methods in allergology focus mainly on the prediction of allergenic proteins, with no information on cross-reactivity patterns among known allergens. In this study, we present AllerTool, a web server with essential tools for the assessment of predicted as well as published cross-reactivity patterns of allergens. The analysis tools include graphical representation of allergen cross-reactivity information; a local sequence comparison tool that displays information of known cross-reactive allergens; a sequence similarity search tool for assessment of cross-reactivity in accordance to FAO/WHO Codex alimentarius guidelines; and a method based on support vector machine (SVM). A 10-fold cross-validation results showed that the area under the receiver operating curve (A(ROC)) of SVM models is 0.90 with 86.00% sensitivity (SE) at specificity (SP) of 86.00%. AllerTool is freely available at http://research.i2r.a-star.edu.sg/AllerTool/.

Reverse micelles as a tool for probing solvent modulation of protein dynamics: Reverse micelle encapsulated hemoglobin☆

OpenAIRE

Roche, Camille J.; Dantsker, David; Heller, Elizabeth R.; Sabat, Joseph E.; Friedman, Joel M.

2013-01-01

Hydration waters impact protein dynamics. Dissecting the interplay between hydration waters and dynamics requires a protein that manifests a broad range of dynamics. Proteins in reverse micelles (RMs) have promise as tools to achieve this objective because the water content can be manipulated. Hemoglobin is an appropriate tool with which to probe hydration effects. We describe both a protocol for hemoglobin encapsulation in reverse micelles and a facile method using PEG and cosolvents to mani...

An Assessment Tool to Integrate Sustainability Principles into the Global Supply Chain

Directory of Open Access Journals (Sweden)

María Jesús Muñoz-Torres

2018-02-01

Full Text Available The integration of sustainability principles into the assessment of companies along the supply chains is a growing research area. However, there is an absence of a generally accepted method to evaluate corporate sustainability performance (CSP, and the models and frameworks proposed by the literature present various important challenges to be addressed. A systematic literature review on the supply chain at the corporate level has been conducted, analyzing the main strengths and gaps in the sustainability assessment literature. Therefore, this paper aims to contribute to the development of this field by proposing an assessment framework a leading company can adopt to expand sustainability principles to the rest of the members of the supply chain. This proposal is based on best practices and integrates and shares efforts with key initiatives (for instance, the Organizational Environmental Footprint from the European Commission and United Nations Environment Programme and the Society of Environmental Toxicology and Chemistry UNEP/SETAC; moreover, it overcomes important limitations of the current sustainability tools in a supply chain context consistent with the circular economy, the Sustainable Development Goals (SDGs, planetary boundaries, and social foundation requirements. The results obtained create, on the one hand, new opportunities for academics; and, on the other hand, in further research, the use of this framework could be a means of actively engaging companies in their supply chains and of achieving the implementation of practical and comprehensive CSP assessment.

Computational tools for experimental determination and theoretical prediction of protein structure

Energy Technology Data Exchange (ETDEWEB)

O`Donoghue, S.; Rost, B.

1995-12-31

This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. The authors intend to review the state of the art in the experimental determination of protein 3D structure (focus on nuclear magnetic resonance), and in the theoretical prediction of protein function and of protein structure in 1D, 2D and 3D from sequence. All the atomic resolution structures determined so far have been derived from either X-ray crystallography (the majority so far) or Nuclear Magnetic Resonance (NMR) Spectroscopy (becoming increasingly more important). The authors briefly describe the physical methods behind both of these techniques; the major computational methods involved will be covered in some detail. They highlight parallels and differences between the methods, and also the current limitations. Special emphasis will be given to techniques which have application to ab initio structure prediction. Large scale sequencing techniques increase the gap between the number of known proteins sequences and that of known protein structures. They describe the scope and principles of methods that contribute successfully to closing that gap. Emphasis will be given on the specification of adequate testing procedures to validate such methods.

Construction of improved tools for protein localization studies in Streptococcus pneumoniae.

Directory of Open Access Journals (Sweden)

Mafalda X Henriques

Full Text Available We have constructed a set of plasmids that allow efficient expression of both N- and C-terminal fusions of proteins of interest to fluorescent proteins mCherry, Citrine, CFP and GFP in the Gram-positive pathogen Streptococcus pneumoniae. In order to improve expression of the fluorescent fusions to levels that allow their detection by fluorescence microscopy, we have introduced a 10 amino acid tag, named i-tag, at the N-terminal end of the fluorescent proteins. This caused increased expression due to improved translation efficiency and did not interfere with the protein localization in pneumococcal bacteria. Localizing fluorescent derivatives of FtsZ, Wzd and Wze in dividing bacteria validated the developed tools. The availability of the new plasmids described in this work should greatly facilitate studies of protein localization in an important clinical pathogen.

A systematic review on popularity, application and characteristics of protein secondary structure prediction tools.

Science.gov (United States)

Kashani-Amin, Elaheh; Tabatabaei-Malazy, Ozra; Sakhteman, Amirhossein; Larijani, Bagher; Ebrahim-Habibi, Azadeh

2018-02-27

Prediction of proteins' secondary structure is one of the major steps in the generation of homology models. These models provide structural information which is used to design suitable ligands for potential medicinal targets. However, selecting a proper tool between multiple secondary structure prediction (SSP) options is challenging. The current study is an insight onto currently favored methods and tools, within various contexts. A systematic review was performed for a comprehensive access to recent (2013-2016) studies which used or recommended protein SSP tools. Three databases, Web of Science, PubMed and Scopus were systematically searched and 99 out of 209 studies were finally found eligible to extract data. Four categories of applications for 59 retrieved SSP tools were: (I) prediction of structural features of a given sequence, (II) evaluation of a method, (III) providing input for a new SSP method and (IV) integrating a SSP tool as a component for a program. PSIPRED was found to be the most popular tool in all four categories. JPred and tools utilizing PHD (Profile network from HeiDelberg) method occupied second and third places of popularity in categories I and II. JPred was only found in the two first categories, while PHD was present in three fields. This study provides a comprehensive insight about the recent usage of SSP tools which could be helpful for selecting a proper tool's choice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Polyacrylamide gel electrophoresis-SDS as a tool to study myofibrillar proteins. A review.

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Perez-Chabela, M. Lourdes

2015-12-01

Full Text Available Miofibrillar proteins are part of land and sea animals’ muscle. Nonetheless, even when muscle proteins are the same type of proteins, their structure, rigor mortis time, and biochemical process associated to muscle to meat conversion, are different among animal species. This review has the aim to describe the advantages of SDS-polyacrylamide gel electrophoresis (SDS-PAGE in the study of myofibrillar proteins structure, besides the influence of many parameters on this technique to obtain an electrophoretic profile. Applications of this technique as a diagnostic tool in the food science, ecology and health are described as well.

Comparative Study of Elastic Network Model and Protein Contact Network for Protein Complexes: The Hemoglobin Case

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Guang Hu

2017-01-01

Full Text Available The overall topology and interfacial interactions play key roles in understanding structural and functional principles of protein complexes. Elastic Network Model (ENM and Protein Contact Network (PCN are two widely used methods for high throughput investigation of structures and interactions within protein complexes. In this work, the comparative analysis of ENM and PCN relative to hemoglobin (Hb was taken as case study. We examine four types of structural and dynamical paradigms, namely, conformational change between different states of Hbs, modular analysis, allosteric mechanisms studies, and interface characterization of an Hb. The comparative study shows that ENM has an advantage in studying dynamical properties and protein-protein interfaces, while PCN is better for describing protein structures quantitatively both from local and from global levels. We suggest that the integration of ENM and PCN would give a potential but powerful tool in structural systems biology.

Computational protein design-the next generation tool to expand synthetic biology applications.

Science.gov (United States)

Gainza-Cirauqui, Pablo; Correia, Bruno Emanuel

2018-05-02

One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology. Here, we review efforts to increase the capabilities of synthetic biology using computational protein design. We focus primarily on computationally designed proteins not only validated in vitro, but also shown to modulate different activities in living cells. Efforts made to validate computational designs in cells can illustrate both the challenges and opportunities in the intersection of protein design and synthetic biology. We also highlight protein design approaches, which although not validated as conveyors of new cellular function in situ, may have rapid and innovative applications in synthetic biology. We foresee that in the near-future, computational protein design will vastly expand the functional capabilities of synthetic cells. Copyright © 2018. Published by Elsevier Ltd.

An efficient but little known tool for the application of the ALARA principle: Isoe (information system on occupational exposure) (in French)

International Nuclear Information System (INIS)

Croq, M.; Mundigl, S.; Lazo, T.; D'Ascenzo, L.; Lefaure, C.

2001-01-01

An efficient but little known tool for the application of the ALARA principle: ISOE (Information System on Occupational Exposure). The Information System on Occupational Exposure to ionizing radiation (ISOE) is a program launched by the Nuclear Energy Agency (NEA) in 1992. It was developed to address the needs of nuclear power plants and safety authorities as a comparison and information tool on practices in terms of optimization (ALARA principle), in NEA member countries. To date, more than 90% of the operating nuclear power plants in the world are participating in this program, which is organized in a decentralized form, with a steering group and four technical centers (Europe, Asia, north America and IAEA). The ISOE program includes an occupational exposure database and an information exchange and communication network. The databases permit the preparation of studies and comparisons of practices, either in a factual or analytical way. Thus, the ISOE program favors exchanges to the benefit of all participants and helps to bring operational radiation protection ever closer towards the 'achievable' of ALARA. (author)

Genomic Enzymology: Web Tools for Leveraging Protein Family Sequence-Function Space and Genome Context to Discover Novel Functions.

Science.gov (United States)

Gerlt, John A

2017-08-22

The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolites/natural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of "genomic enzymology" web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST) for generating sequence similarity networks to visualize and analyze sequence-function space in protein families and (2) Enzyme Function Initiative-Genome Neighborhood Tool (EFI-GNT) for generating genome neighborhood networks to visualize and analyze the genome context in microbial and fungal genomes. Both tools have been adapted to other applications to facilitate target selection for enzyme discovery and functional characterization. As the natural products community has demonstrated, the enzymology community needs to embrace the essential role of web tools that allow the protein and genome sequence databases to be leveraged for novel insights into enzymological problems.

A first-principles model of early evolution: emergence of gene families, species, and preferred protein folds.

Directory of Open Access Journals (Sweden)

Konstantin B Zeldovich

2007-07-01

Full Text Available In this work we develop a microscopic physical model of early evolution where phenotype--organism life expectancy--is directly related to genotype--the stability of its proteins in their native conformations-which can be determined exactly in the model. Simulating the model on a computer, we consistently observe the "Big Bang" scenario whereby exponential population growth ensues as soon as favorable sequence-structure combinations (precursors of stable proteins are discovered. Upon that, random diversity of the structural space abruptly collapses into a small set of preferred proteins. We observe that protein folds remain stable and abundant in the population at timescales much greater than mutation or organism lifetime, and the distribution of the lifetimes of dominant folds in a population approximately follows a power law. The separation of evolutionary timescales between discovery of new folds and generation of new sequences gives rise to emergence of protein families and superfamilies whose sizes are power-law distributed, closely matching the same distributions for real proteins. On the population level we observe emergence of species--subpopulations that carry similar genomes. Further, we present a simple theory that relates stability of evolving proteins to the sizes of emerging genomes. Together, these results provide a microscopic first-principles picture of how first-gene families developed in the course of early evolution.

Reverse micelles as a tool for probing solvent modulation of protein dynamics: Reverse micelle encapsulated hemoglobin

Science.gov (United States)

Roche, Camille J.; Dantsker, David; Heller, Elizabeth R.; Sabat, Joseph E.; Friedman, Joel M.

2013-08-01

Hydration waters impact protein dynamics. Dissecting the interplay between hydration waters and dynamics requires a protein that manifests a broad range of dynamics. Proteins in reverse micelles (RMs) have promise as tools to achieve this objective because the water content can be manipulated. Hemoglobin is an appropriate tool with which to probe hydration effects. We describe both a protocol for hemoglobin encapsulation in reverse micelles and a facile method using PEG and cosolvents to manipulate water content. Hydration properties are probed using the water-sensitive fluorescence from Hb bound pyranine and covalently attached Badan. Protein dynamics are probed through ligand recombination traces derived from photodissociated carbonmonoxy hemoglobin on a log scale that exposes the potential role of both α and β solvent fluctuations in modulating protein dynamics. The results open the possibility of probing hydration level phenomena in this system using a combination of NMR and optical probes.

Identification of similar regions of protein structures using integrated sequence and structure analysis tools

Directory of Open Access Journals (Sweden)

Heiland Randy

2006-03-01

Full Text Available Abstract Background Understanding protein function from its structure is a challenging problem. Sequence based approaches for finding homology have broad use for annotation of both structure and function. 3D structural information of protein domains and their interactions provide a complementary view to structure function relationships to sequence information. We have developed a web site http://www.sblest.org/ and an API of web services that enables users to submit protein structures and identify statistically significant neighbors and the underlying structural environments that make that match using a suite of sequence and structure analysis tools. To do this, we have integrated S-BLEST, PSI-BLAST and HMMer based superfamily predictions to give a unique integrated view to prediction of SCOP superfamilies, EC number, and GO term, as well as identification of the protein structural environments that are associated with that prediction. Additionally, we have extended UCSF Chimera and PyMOL to support our web services, so that users can characterize their own proteins of interest. Results Users are able to submit their own queries or use a structure already in the PDB. Currently the databases that a user can query include the popular structural datasets ASTRAL 40 v1.69, ASTRAL 95 v1.69, CLUSTER50, CLUSTER70 and CLUSTER90 and PDBSELECT25. The results can be downloaded directly from the site and include function prediction, analysis of the most conserved environments and automated annotation of query proteins. These results reflect both the hits found with PSI-BLAST, HMMer and with S-BLEST. We have evaluated how well annotation transfer can be performed on SCOP ID's, Gene Ontology (GO ID's and EC Numbers. The method is very efficient and totally automated, generally taking around fifteen minutes for a 400 residue protein. Conclusion With structural genomics initiatives determining structures with little, if any, functional characterization

Variational principles in physics

CERN Document Server

Basdevant, Jean-Louis

2007-01-01

Optimization under constraints is an essential part of everyday life. Indeed, we routinely solve problems by striking a balance between contradictory interests, individual desires and material contingencies. This notion of equilibrium was dear to thinkers of the enlightenment, as illustrated by Montesquieu’s famous formulation: "In all magistracies, the greatness of the power must be compensated by the brevity of the duration." Astonishingly, natural laws are guided by a similar principle. Variational principles have proven to be surprisingly fertile. For example, Fermat used variational methods to demonstrate that light follows the fastest route from one point to another, an idea which came to be known as Fermat’s principle, a cornerstone of geometrical optics. Variational Principles in Physics explains variational principles and charts their use throughout modern physics. The heart of the book is devoted to the analytical mechanics of Lagrange and Hamilton, the basic tools of any physicist. Prof. Basdev...

Solid state nuclear magnetic resonance studies of prion peptides and proteins

Energy Technology Data Exchange (ETDEWEB)

Heller, Jonathan [Univ. of California, Berkeley, CA (United States)

1997-08-01

High-resolution structural studies using x-ray diffraction and solution nuclear magnetic resonance (NMR) are not feasible for proteins of low volubility and high tendency to aggregate. Solid state NMR (SSNMR) is in principle capable of providing structural information in such systems, however to do this efficiently and accurately, further SSNMR tools must be developed This dissertation describes the development of three new methods and their application to a biological system of interest, the priori protein (PrP).

Common principles and multiculturalism.

Science.gov (United States)

Zahedi, Farzaneh; Larijani, Bagher

2009-01-01

Judgment on rightness and wrongness of beliefs and behaviors is a main issue in bioethics. Over centuries, big philosophers and ethicists have been discussing the suitable tools to determine which act is morally sound and which one is not. Emerging the contemporary bioethics in the West has resulted in a misconception that absolute westernized principles would be appropriate tools for ethical decision making in different cultures. We will discuss this issue by introducing a clinical case. Considering various cultural beliefs around the world, though it is not logical to consider all of them ethically acceptable, we can gather on some general fundamental principles instead of going to the extremes of relativism and absolutism. Islamic teachings, according to the presented evidence in this paper, fall in with this idea.

Common Principles and Multiculturalism

Science.gov (United States)

Zahedi, Farzaneh; Larijani, Bagher

2009-01-01

Judgment on rightness and wrongness of beliefs and behaviors is a main issue in bioethics. Over centuries, big philosophers and ethicists have been discussing the suitable tools to determine which act is morally sound and which one is not. Emerging the contemporary bioethics in the West has resulted in a misconception that absolute westernized principles would be appropriate tools for ethical decision making in different cultures. We will discuss this issue by introducing a clinical case. Considering various cultural beliefs around the world, though it is not logical to consider all of them ethically acceptable, we can gather on some general fundamental principles instead of going to the extremes of relativism and absolutism. Islamic teachings, according to the presented evidence in this paper, fall in with this idea. PMID:23908720

PIMiner: A web tool for extraction of protein interactions from biomedical literature

KAUST Repository

Chowdhary, Rajesh

2013-01-01

Information on Protein Interactions (PIs) is valuable for biomedical research, but often lies buried in the scientific literature and cannot be readily retrieved. While much progress has been made over the years in extracting PIs from the literature using computational methods, there is a lack of free, public, user-friendly tools for the discovery of PIs. We developed an online tool for the extraction of PI relationships from PubMed-abstracts, which we name PIMiner. Protein pairs and the words that describe their interactions are reported by PIMiner so that new interactions can be easily detected within text. The interaction likelihood levels are reported too. The option to extract only specific types of interactions is also provided. The PIMiner server can be accessed through a web browser or remotely through a client\\'s command line. PIMiner can process 50,000 PubMed abstracts in approximately 7 min and thus appears suitable for large-scale processing of biological/biomedical literature. Copyright © 2013 Inderscience Enterprises Ltd.

[The template principle: paradigm of modern genetics].

Science.gov (United States)

Inge-Vechtomov, S G

2013-01-01

The idea of continuity in living systems, which was initially developed in mid-19th century, reached its peak in 1928 thanks to N.K. Koltsov, who proposed the template principle in chromosome reproduction. The determination of genetic functions of nucleic acids and the advent of molecular genetics led to F. Crick's statement of the central dogma of molecular biology in 1958. This dogma became a contemporary version of the template principle (templates of the first order). The discovery of "protein inheritance" underlay the notion of steric or conformational templates (second order) for reproducing conformation in a number of proteins. The template principle supplemented by this notion claims to be the main paradigm of modern genetics.

A convenient tool for gas derivatization using fine-needle capillary mounting for protein crystals

International Nuclear Information System (INIS)

Mizuno, Nobuhiro; Makino, Masatomo; Kumasaka, Takashi

2013-01-01

A convenient gas-derivatization tool for protein crystals is presented in combination with a fine-needle capillary and a gas-pressure regulator. Gas derivatization of protein crystals is useful not only to analyse gas-binding proteins but also to solve the phase problem of X-ray crystallography by using noble gases. However, the gas pressurization tools for these experiments are often elaborate and need to release the gas before flash-cooling. To simplify this step, a procedure using a fine-needle capillary to mount and flash-cool protein crystals under the pressurization of gases has been developed. After the crystals are picked up with the capillary, the capillary is sealed with an adhesive and then connected directly to a gas regulator. The quality of the diffraction data using this method is comparable with that of data from conventional pressurization procedures. The preparation of xenon-derivatives of hen egg-white lysozyme using this method was a success. In the derivatives, two new xenon binding sites were found and one of their sites vanished by releasing the gas. This observation shows the availability of flash-cooling under gas pressurization. This procedure is simple and useful for preparing gas-derivative crystals

On the invariance principle

Energy Technology Data Exchange (ETDEWEB)

Moller-Nielsen, Thomas [University of Oxford (United Kingdom)

2014-07-01

Physicists and philosophers have long claimed that the symmetries of our physical theories - roughly speaking, those transformations which map solutions of the theory into solutions - can provide us with genuine insight into what the world is really like. According to this 'Invariance Principle', only those quantities which are invariant under a theory's symmetries should be taken to be physically real, while those quantities which vary under its symmetries should not. Physicists and philosophers, however, are generally divided (or, indeed, silent) when it comes to explaining how such a principle is to be justified. In this paper, I spell out some of the problems inherent in other theorists' attempts to justify this principle, and sketch my own proposed general schema for explaining how - and when - the Invariance Principle can indeed be used as a legitimate tool of metaphysical inference.

iQuantitator: A tool for protein expression inference using iTRAQ

Directory of Open Access Journals (Sweden)

Comte-Walters Susana

2009-10-01

Full Text Available Abstract Background Isobaric Tags for Relative and Absolute Quantitation (iTRAQ™ [Applied Biosystems] have seen increased application in differential protein expression analysis. To facilitate the growing need to analyze iTRAQ data, especially for cases involving multiple iTRAQ experiments, we have developed a modeling approach, statistical methods, and tools for estimating the relative changes in protein expression under various treatments and experimental conditions. Results This modeling approach provides a unified analysis of data from multiple iTRAQ experiments and links the observed quantity (reporter ion peak area to the experiment design and the calculated quantity of interest (treatment-dependent protein and peptide fold change through an additive model under log transformation. Others have demonstrated, through a case study, this modeling approach and noted the computational challenges of parameter inference in the unbalanced data set typical of multiple iTRAQ experiments. Here we present the development of an inference approach, based on hierarchical regression with batching of regression coefficients and Markov Chain Monte Carlo (MCMC methods that overcomes some of these challenges. In addition to our discussion of the underlying method, we also present our implementation of the software, simulation results, experimental results, and sample output from the resulting analysis report. Conclusion iQuantitator's process-based modeling approach overcomes limitations in current methods and allows for application in a variety of experimental designs. Additionally, hypertext-linked documents produced by the tool aid in the interpretation and exploration of results.

PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modifications.

Science.gov (United States)

Chaudhuri, Rima; Sadrieh, Arash; Hoffman, Nolan J; Parker, Benjamin L; Humphrey, Sean J; Stöckli, Jacqueline; Hill, Adam P; James, David E; Yang, Jean Yee Hwa

2015-08-19

Most biological processes are influenced by protein post-translational modifications (PTMs). Identifying novel PTM sites in different organisms, including humans and model organisms, has expedited our understanding of key signal transduction mechanisms. However, with increasing availability of deep, quantitative datasets in diverse species, there is a growing need for tools to facilitate cross-species comparison of PTM data. This is particularly important because functionally important modification sites are more likely to be evolutionarily conserved; yet cross-species comparison of PTMs is difficult since they often lie in structurally disordered protein domains. Current tools that address this can only map known PTMs between species based on known orthologous phosphosites, and do not enable the cross-species mapping of newly identified modification sites. Here, we addressed this by developing a web-based software tool, PhosphOrtholog ( www.phosphortholog.com ) that accurately maps protein modification sites between different species. This facilitates the comparison of datasets derived from multiple species, and should be a valuable tool for the proteomics community. Here we describe PhosphOrtholog, a web-based application for mapping known and novel orthologous PTM sites from experimental data obtained from different species. PhosphOrtholog is the only generic and automated tool that enables cross-species comparison of large-scale PTM datasets without relying on existing PTM databases. This is achieved through pairwise sequence alignment of orthologous protein residues. To demonstrate its utility we apply it to two sets of human and rat muscle phosphoproteomes generated following insulin and exercise stimulation, respectively, and one publicly available mouse phosphoproteome following cellular stress revealing high mapping and coverage efficiency. Although coverage statistics are dataset dependent, PhosphOrtholog increased the number of cross-species mapped sites

Green Fluorescent Protein Purification as a Didactic Tool During Practical Classes For Undergraduates Students of UFAM

Directory of Open Access Journals (Sweden)

J.A.Q.A Faria

2017-07-01

Full Text Available INTRODUCTION: The Green Fluorescent Protein (GFP, originated from the jellyfish Aequorea victoria has broadly applicability for cellular and molecular biology research. Its spectral characteristics make it practical  to be detect by UV-A (black light lamp during the purification procedure. Moreover, this approach implementation during a practical class allows the exploring of fluorescence features. OBJETIVES: the purpose of this investigation was to teach the concepts and principles of protein purification during a practical class using recombinant GFP protein. MATERIAL E METHODS: Transformed E. coli JM110 expressing GFP were resuspended in buffer solution (Tris-HCl 20 mM pH 8.0, 150 mM NaCl, 5 mM EDTA, 20% (NH42SO4 following the sonication step. The lysate was submitted to the purification through hydrophobic interaction chromatography column (HIC. After analysis of chromatogram, some collected fractions were quantified by Bradford assay and evaluated by SDS-PAGE. Besides that, the GFP presences were measured at an excitation wavelength of 488 nm on a spectrofluorimeter. RESULTS AND DISCUSSION: Before the experiments, the students were encouraged to explore the biochemistry characteristics of GFP, assessing protein data banks and published articles. These guided questions conducted to discussion of the purification strategy choosen. The GFP purification enabled the visual observation of chromatography principles necessary for the theory assimilation. During the chromatography running, we used a UV-A lamp which allowed a greatly exploration of concepts beyond this technique such as the sample injection, the GFP column retention, and the elution step. The chromatogram obtaneid were analysed and correlated to the collected fractions. Our next step was the efficiency analysis generated by the GFP measurement, total protein quantification and the analytical method SDS-PAGE. CONCLUSION: Collectively, we observed in this class the clear development

Tools and procedures for visualization of proteins and other biomolecules.

Science.gov (United States)

Pan, Lurong; Aller, Stephen G

2015-04-01

Protein, peptides, and nucleic acids are biomolecules that drive biological processes in living organisms. An enormous amount of structural data for a large number of these biomolecules has been described with atomic precision in the form of structural "snapshots" that are freely available in public repositories. These snapshots can help explain how the biomolecules function, the nature of interactions between multi-molecular complexes, and even how small-molecule drugs can modulate the biomolecules for clinical benefits. Furthermore, these structural snapshots serve as inputs for sophisticated computer simulations to turn the biomolecules into moving, "breathing" molecular machines for understanding their dynamic properties in real-time computer simulations. In order for the researcher to take advantage of such a wealth of structural data, it is necessary to gain competency in the use of computer molecular visualization tools for exploring the structures and visualizing three-dimensional spatial representations. Here, we present protocols for using two common visualization tools--the Web-based Jmol and the stand-alone PyMOL package--as well as a few examples of other popular tools. Copyright © 2015 John Wiley & Sons, Inc.

Species and tissues specific differentiation of processed animal proteins in aquafeeds using proteomics tools.

Science.gov (United States)

Rasinger, J D; Marbaix, H; Dieu, M; Fumière, O; Mauro, S; Palmblad, M; Raes, M; Berntssen, M H G

2016-09-16

The rapidly growing aquaculture industry drives the search for sustainable protein sources in fish feed. In the European Union (EU) since 2013 non-ruminant processed animal proteins (PAP) are again permitted to be used in aquafeeds. To ensure that commercial fish feeds do not contain PAP from prohibited species, EU reference methods were established. However, due to the heterogeneous and complex nature of PAP complementary methods are required to guarantee the safe use of this fish feed ingredient. In addition, there is a need for tissue specific PAP detection to identify the sources (i.e. bovine carcass, blood, or meat) of illegal PAP use. In the present study, we investigated and compared different protein extraction, solubilisation and digestion protocols on different proteomics platforms for the detection and differentiation of prohibited PAP. In addition, we assessed if tissue specific PAP detection was feasible using proteomics tools. All work was performed independently in two different laboratories. We found that irrespective of sample preparation gel-based proteomics tools were inappropriate when working with PAP. Gel-free shotgun proteomics approaches in combination with direct spectral comparison were able to provide quality species and tissue specific data to complement and refine current methods of PAP detection and identification. To guarantee the safe use of processed animal protein (PAP) in aquafeeds efficient PAP detection and monitoring tools are required. The present study investigated and compared various proteomics workflows and shows that the application of shotgun proteomics in combination with direct comparison of spectral libraries provides for the desired species and tissue specific classification of this heat sterilized and pressure treated (≥133°C, at 3bar for 20min) protein feed ingredient. Copyright © 2016 Elsevier B.V. All rights reserved.

SPiCE : A web-based tool for sequence-based protein classification and exploration

NARCIS (Netherlands)

Van den Berg, B.A.; Reinders, M.J.; Roubos, J.A.; De Ridder, D.

2014-01-01

Background Amino acid sequences and features extracted from such sequences have been used to predict many protein properties, such as subcellular localization or solubility, using classifier algorithms. Although software tools are available for both feature extraction and classifier construction,

Cytosolic fatty acid-binding proteins: subjects and tools in metabolic research

Energy Technology Data Exchange (ETDEWEB)

Binas, B. [Max Delbrueck Center for Molecular Medicine, Berlin-Buch (Germany)

1998-12-31

Fatty acid-binding proteins (FABPs) are major targets for specific binding of fatty acids in vivo. They constitute a widely expressed family of genetically related, small cytosolic proteins which very likely mediate intracellular transport of free long chain fatty acids. Genetic inhibition of FABP expression in vivo should therefore provide a useful tool to investigate and engineer fatty acid metabolism. (orig.) [Deutsch] Fettsaeurebindungsproteine (FABPs) sind wichtige Bindungsstellen fuer Fettsaeuren in vivo; sie bilden eine breit exprimierte Familie genetisch verwandter kleiner Zytosoleiweisse, die sehr wahrscheinlich den intrazellulaeren Transport unveresterter langkettiger Fettsaeuren vermitteln. Die genetische Hemmung der FABP-Expanssion in vivo bietet sich deshalb als Werkzeug zur Erforschung und gezielten Veraenderung des Fettsaeurestoffwechsels an. (orig.)

Next-Generation Sequencing for Binary Protein-Protein Interactions

Directory of Open Access Journals (Sweden)

Bernhard eSuter

2015-12-01

Full Text Available The yeast two-hybrid (Y2H system exploits host cell genetics in order to display binary protein-protein interactions (PPIs via defined and selectable phenotypes. Numerous improvements have been made to this method, adapting the screening principle for diverse applications, including drug discovery and the scale-up for proteome wide interaction screens in human and other organisms. Here we discuss a systematic workflow and analysis scheme for screening data generated by Y2H and related assays that includes high-throughput selection procedures, readout of comprehensive results via next-generation sequencing (NGS, and the interpretation of interaction data via quantitative statistics. The novel assays and tools will serve the broader scientific community to harness the power of NGS technology to address PPI networks in health and disease. We discuss examples of how this next-generation platform can be applied to address specific questions in diverse fields of biology and medicine.

Aligator: A computational tool for optimizing total chemical synthesis of large proteins.

Science.gov (United States)

Jacobsen, Michael T; Erickson, Patrick W; Kay, Michael S

2017-09-15

The scope of chemical protein synthesis (CPS) continues to expand, driven primarily by advances in chemical ligation tools (e.g., reversible solubilizing groups and novel ligation chemistries). However, the design of an optimal synthesis route can be an arduous and fickle task due to the large number of theoretically possible, and in many cases problematic, synthetic strategies. In this perspective, we highlight recent CPS tool advances and then introduce a new and easy-to-use program, Aligator (Automated Ligator), for analyzing and designing the most efficient strategies for constructing large targets using CPS. As a model set, we selected the E. coli ribosomal proteins and associated factors for computational analysis. Aligator systematically scores and ranks all feasible synthetic strategies for a particular CPS target. The Aligator script methodically evaluates potential peptide segments for a target using a scoring function that includes solubility, ligation site quality, segment lengths, and number of ligations to provide a ranked list of potential synthetic strategies. We demonstrate the utility of Aligator by analyzing three recent CPS projects from our lab: TNFα (157 aa), GroES (97 aa), and DapA (312 aa). As the limits of CPS are extended, we expect that computational tools will play an increasingly important role in the efficient execution of ambitious CPS projects such as production of a mirror-image ribosome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Climate-responsive design: A framework for an energy concept design-decision support tool for architects using principles of climate-responsive design

Directory of Open Access Journals (Sweden)

Remco Looman

2017-01-01

Full Text Available In climate-responsive design the building becomes an intermediary in its own energy housekeeping, forming a link between the harvest of climate resources and low energy provision of comfort. Essential here is the employment of climate-responsive building elements, defined as structural and architectural elements in which the energy infrastructure is far-reaching integrated. This thesis presents the results of research conducted on what knowledge is needed in the early stages of the design process and how to transfer and transform that knowledge to the field of the architect in order for them to successfully implement the principles of climate-responsive design. The derived content, form and functional requirements provide the framework for a design decision support tool. These requirements were incorporated into a concept tool that has been presented to architects in the field, in order to gain their feedback. Climate-responsive design makes the complex task of designing even more complex. Architects are helped when sufficient information on the basics of climate-responsive design and its implications are provided as informative support during decision making in the early design stages of analysis and energy concept development. This informative support on climate-responsive design should address to different design styles in order to be useful to any type of architects. What is defined as comfortable has far-reaching implications for the way buildings are designed and how they operate. This in turn gives an indication of the energy used for maintaining a comfortable indoor environment. Comfort is not a strict situation, but subjective. Diversity is appreciated and comfort is improved when users have the ability to exert influence on their environment. Historically, the provision of comfort has led to the adoption of mechanical climate control systems that operate in many cases indifferent from the building space and mass and its environment

Common Principles and Multiculturalism

OpenAIRE

Zahedi, Farzaneh; Larijani, Bagher

2009-01-01

Judgment on rightness and wrongness of beliefs and behaviors is a main issue in bioethics. Over centuries, big philosophers and ethicists have been discussing the suitable tools to determine which act is morally sound and which one is not. Emerging the contemporary bioethics in the West has resulted in a misconception that absolute westernized principles would be appropriate tools for ethical decision making in different cultures. We will discuss this issue by introducing a clinical case. Con...

Affinity resins as new tools for identifying target proteins of ascorbic acid.

Science.gov (United States)

Iwaoka, Yuji; Nishino, Kohei; Ishikawa, Takahiro; Ito, Hideyuki; Sawa, Yoshihiro; Tai, Akihiro

2018-02-12

l-Ascorbic acid (AA) has diverse physiological functions, but little is known about the functional mechanisms of AA. In this study, we synthesized two types of affinity resin on which AA is immobilized in a stable form to identify new AA-targeted proteins, which can provide important clues for elucidating unknown functional mechanisms of AA. To our knowledge, an affinity resin on which AA as a ligand is immobilized has not been prepared, because AA is very unstable and rapidly degraded in an aqueous solution. By using the affinity resins, cytochrome c (cyt c) was identified as an AA-targeted protein, and we showed that oxidized cyt c exhibits specific affinity for AA. These results suggest that two kinds of AA-affinity resin can be powerful tools to identify new target proteins of AA.

Locating proteins in the cell using TargetP, SignalP and related tools

DEFF Research Database (Denmark)

Emanuelsson, O.; Brunak, Søren; von Heijne, G.

2007-01-01

of methods to predict subcellular localization based on these sorting signals and other sequence properties. We then outline how to use a number of internet-accessible tools to arrive at a reliable subcellular localization prediction for eukaryotic and prokaryotic proteins. In particular, we provide detailed...

The precautionary principle: is it safe.

Science.gov (United States)

Gignon, Maxime; Ganry, Olivier; Jardé, Olivier; Manaouil, Cécile

2013-06-01

The precautionary principle is generally acknowledged to be a powerful tool for protecting health but it was originally invoked by policy makers for dealing with environmental issues. In the 1990s, the principle was incorporated into many legislative and regulatory texts in international law. One can consider that the precautionary principle has turned into "precautionism" necessary to prove to the people, taking account of risk in decisions. There is now a risk that these abuses will deprive the principle of its meaning and value. When pushed to its limits, the precautionary principle can even be dangerous when applied to the healthcare field. This is why a critical analysis of the principle is necessary. Through the literature, it sometimes seems to deviate somehow from the essence of the precautionary principle as it is commonly used in relation to health. We believe that educational work is necessary to familiarize professionals, policy makers and public opinion of the precautionary principle and avoid confusion. We propose a critical analysis of the use and misuse of the precautionary principle.

The carnegie protein trap library: a versatile tool for Drosophila developmental studies.

Science.gov (United States)

Buszczak, Michael; Paterno, Shelley; Lighthouse, Daniel; Bachman, Julia; Planck, Jamie; Owen, Stephenie; Skora, Andrew D; Nystul, Todd G; Ohlstein, Benjamin; Allen, Anna; Wilhelm, James E; Murphy, Terence D; Levis, Robert W; Matunis, Erika; Srivali, Nahathai; Hoskins, Roger A; Spradling, Allan C

2007-03-01

Metazoan physiology depends on intricate patterns of gene expression that remain poorly known. Using transposon mutagenesis in Drosophila, we constructed a library of 7404 protein trap and enhancer trap lines, the Carnegie collection, to facilitate gene expression mapping at single-cell resolution. By sequencing the genomic insertion sites, determining splicing patterns downstream of the enhanced green fluorescent protein (EGFP) exon, and analyzing expression patterns in the ovary and salivary gland, we found that 600-900 different genes are trapped in our collection. A core set of 244 lines trapped different identifiable protein isoforms, while insertions likely to act as GFP-enhancer traps were found in 256 additional genes. At least 8 novel genes were also identified. Our results demonstrate that the Carnegie collection will be useful as a discovery tool in diverse areas of cell and developmental biology and suggest new strategies for greatly increasing the coverage of the Drosophila proteome with protein trap insertions.

Using the Tools and Resources of the RCSB Protein Data Bank.

Science.gov (United States)

Costanzo, Luigi Di; Ghosh, Sutapa; Zardecki, Christine; Burley, Stephen K

2016-09-07

The Protein Data Bank (PDB) archive is the worldwide repository of experimentally determined three-dimensional structures of large biological molecules found in all three kingdoms of life. Atomic-level structures of these proteins, nucleic acids, and complex assemblies thereof are central to research and education in molecular, cellular, and organismal biology, biochemistry, biophysics, materials science, bioengineering, ecology, and medicine. Several types of information are associated with each PDB archival entry, including atomic coordinates, primary experimental data, polymer sequence(s), and summary metadata. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) serves as the U.S. data center for the PDB, distributing archival data and supporting both simple and complex queries that return results. These data can be freely downloaded, analyzed, and visualized using RCSB PDB tools and resources to gain a deeper understanding of fundamental biological processes, molecular evolution, human health and disease, and drug discovery. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

On the analysis of protein-protein interactions via knowledge-based potentials for the prediction of protein-protein docking

DEFF Research Database (Denmark)

Feliu, Elisenda; Aloy, Patrick; Oliva, Baldo

2011-01-01

Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions for s...... and with independence of the partner. This information is encoded at the residue level and could be easily incorporated in the initial grid scoring for Fast Fourier Transform rigid-body docking methods.......Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions...... for selecting rigid-body docking poses. These potentials include the energetic component that provides the residues with a particular secondary structure and surface accessibility. These scoring functions have been tested on a state-of-art benchmark dataset and on a decoy dataset of permanent interactions. Our...

New tools and functions in data-out activities at Protein Data Bank Japan (PDBj).

Science.gov (United States)

Kinjo, Akira R; Bekker, Gert-Jan; Wako, Hiroshi; Endo, Shigeru; Tsuchiya, Yuko; Sato, Hiromu; Nishi, Hafumi; Kinoshita, Kengo; Suzuki, Hirofumi; Kawabata, Takeshi; Yokochi, Masashi; Iwata, Takeshi; Kobayashi, Naohiro; Fujiwara, Toshimichi; Kurisu, Genji; Nakamura, Haruki

2018-01-01

The Protein Data Bank Japan (PDBj), a member of the worldwide Protein Data Bank (wwPDB), accepts and processes the deposited data of experimentally determined biological macromolecular structures. In addition to archiving the PDB data in collaboration with the other wwPDB partners, PDBj also provides a wide range of original and unique services and tools, which are continuously improved and updated. Here, we report the new RDB PDBj Mine 2, the WebGL molecular viewer Molmil, the ProMode-Elastic server for normal mode analysis, a virtual reality system for the eF-site protein electrostatic molecular surfaces, the extensions of the Omokage search for molecular shape similarity, and the integration of PDBj and BMRB searches. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

MSX-3D: a tool to validate 3D protein models using mass spectrometry.

Science.gov (United States)

Heymann, Michaël; Paramelle, David; Subra, Gilles; Forest, Eric; Martinez, Jean; Geourjon, Christophe; Deléage, Gilbert

2008-12-01

The technique of chemical cross-linking followed by mass spectrometry has proven to bring valuable information about the protein structure and interactions between proteic subunits. It is an effective and efficient way to experimentally investigate some aspects of a protein structure when NMR and X-ray crystallography data are lacking. We introduce MSX-3D, a tool specifically geared to validate protein models using mass spectrometry. In addition to classical peptides identifications, it allows an interactive 3D visualization of the distance constraints derived from a cross-linking experiment. Freely available at http://proteomics-pbil.ibcp.fr

DichroMatch at the protein circular dichroism data bank (DM@PCDDB): A web-based tool for identifying protein nearest neighbors using circular dichroism spectroscopy.

Science.gov (United States)

Whitmore, Lee; Mavridis, Lazaros; Wallace, B A; Janes, Robert W

2018-01-01

Circular dichroism spectroscopy is a well-used, but simple method in structural biology for providing information on the secondary structure and folds of proteins. DichroMatch (DM@PCDDB) is an online tool that is newly available in the Protein Circular Dichroism Data Bank (PCDDB), which takes advantage of the wealth of spectral and metadata deposited therein, to enable identification of spectral nearest neighbors of a query protein based on four different methods of spectral matching. DM@PCDDB can potentially provide novel information about structural relationships between proteins and can be used in comparison studies of protein homologs and orthologs. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

Synchrotron radiation, a powerful tool in research and technological development. Basic principles

International Nuclear Information System (INIS)

Jimenez M, J.

2001-01-01

The basic principles of synchrotron radiation emission in electron accelerators are presented. The main characteristics of synchrotron radiation, together with the physical principles that describe its interaction with different materials are also discussed. Different areas in which the development of synchrotron radiation has made a major impact are given. (Author)

Principles of mathematical modeling

CERN Document Server

Dym, Clive

2004-01-01

Science and engineering students depend heavily on concepts of mathematical modeling. In an age where almost everything is done on a computer, author Clive Dym believes that students need to understand and "own" the underlying mathematics that computers are doing on their behalf. His goal for Principles of Mathematical Modeling, Second Edition, is to engage the student reader in developing a foundational understanding of the subject that will serve them well into their careers. The first half of the book begins with a clearly defined set of modeling principles, and then introduces a set of foundational tools including dimensional analysis, scaling techniques, and approximation and validation techniques. The second half demonstrates the latest applications for these tools to a broad variety of subjects, including exponential growth and decay in fields ranging from biology to economics, traffic flow, free and forced vibration of mechanical and other systems, and optimization problems in biology, structures, an...

SA-Search: a web tool for protein structure mining based on a Structural Alphabet

OpenAIRE

Guyon, Frédéric; Camproux, Anne-Claude; Hochez, Joëlle; Tufféry, Pierre

2004-01-01

SA-Search is a web tool that can be used to mine for protein structures and extract structural similarities. It is based on a hidden Markov model derived Structural Alphabet (SA) that allows the compression of three-dimensional (3D) protein conformations into a one-dimensional (1D) representation using a limited number of prototype conformations. Using such a representation, classical methods developed for amino acid sequences can be employed. Currently, SA-Search permits the performance of f...

Teaching the Principles of Economics

OpenAIRE

N. Gregory Mankiw

1998-01-01

In this brief essay, I describe my approach to the principles course. I emphasize three themes. First, in teaching microeconomics, the tools of welfare economics should play a larger role than they have in the past. Second, in teaching macroeconomics, classical ideas should play a larger role than they have in the past. Third, in teaching all parts of the course, we instructors should be sure to stress the important principles and be careful not to overwhelm students with an excess of details.

MyPMFs: a simple tool for creating statistical potentials to assess protein structural models.

Science.gov (United States)

Postic, Guillaume; Hamelryck, Thomas; Chomilier, Jacques; Stratmann, Dirk

2018-05-29

Evaluating the model quality of protein structures that evolve in environments with particular physicochemical properties requires scoring functions that are adapted to their specific residue compositions and/or structural characteristics. Thus, computational methods developed for structures from the cytosol cannot work properly on membrane or secreted proteins. Here, we present MyPMFs, an easy-to-use tool that allows users to train statistical potentials of mean force (PMFs) on the protein structures of their choice, with all parameters being adjustable. We demonstrate its use by creating an accurate statistical potential for transmembrane protein domains. We also show its usefulness to study the influence of the physical environment on residue interactions within protein structures. Our open-source software is freely available for download at https://github.com/bibip-impmc/mypmfs. Copyright © 2018. Published by Elsevier B.V.

Development of a Model Protein Interaction Pair as a Benchmarking Tool for the Quantitative Analysis of 2-Site Protein-Protein Interactions.

Science.gov (United States)

Yamniuk, Aaron P; Newitt, John A; Doyle, Michael L; Arisaka, Fumio; Giannetti, Anthony M; Hensley, Preston; Myszka, David G; Schwarz, Fred P; Thomson, James A; Eisenstein, Edward

2015-12-01

A significant challenge in the molecular interaction field is to accurately determine the stoichiometry and stepwise binding affinity constants for macromolecules having >1 binding site. The mission of the Molecular Interactions Research Group (MIRG) of the Association of Biomolecular Resource Facilities (ABRF) is to show how biophysical technologies are used to quantitatively characterize molecular interactions, and to educate the ABRF members and scientific community on the utility and limitations of core technologies [such as biosensor, microcalorimetry, or analytic ultracentrifugation (AUC)]. In the present work, the MIRG has developed a robust model protein interaction pair consisting of a bivalent variant of the Bacillus amyloliquefaciens extracellular RNase barnase and a variant of its natural monovalent intracellular inhibitor protein barstar. It is demonstrated that this system can serve as a benchmarking tool for the quantitative analysis of 2-site protein-protein interactions. The protein interaction pair enables determination of precise binding constants for the barstar protein binding to 2 distinct sites on the bivalent barnase binding partner (termed binase), where the 2 binding sites were engineered to possess affinities that differed by 2 orders of magnitude. Multiple MIRG laboratories characterized the interaction using isothermal titration calorimetry (ITC), AUC, and surface plasmon resonance (SPR) methods to evaluate the feasibility of the system as a benchmarking model. Although general agreement was seen for the binding constants measured using solution-based ITC and AUC approaches, weaker affinity was seen for surface-based method SPR, with protein immobilization likely affecting affinity. An analysis of the results from multiple MIRG laboratories suggests that the bivalent barnase-barstar system is a suitable model for benchmarking new approaches for the quantitative characterization of complex biomolecular interactions.

The neutron porosity tool

International Nuclear Information System (INIS)

Oelgaard, P.L.

1988-01-01

The report contains a review of available information on neutron porosity tools with the emphasis on dual thermal-neutron-detector porosity tools and epithermal-neutron-detector porosity tools. The general principle of such tools is discussed and theoretical models are very briefly reviewed. Available data on tool designs are summarized with special regard to the source-detector distance. Tool operational data, porosity determination and correction of measurements are briefly discussed. (author) 15 refs

New user-friendly approach to obtain an Eisenberg plot and its use as a practical tool in protein sequence analysis.

Science.gov (United States)

Keller, Rob C A

2011-01-01

The Eisenberg plot or hydrophobic moment plot methodology is one of the most frequently used methods of bioinformatics. Bioinformatics is more and more recognized as a helpful tool in Life Sciences in general, and recent developments in approaches recognizing lipid binding regions in proteins are promising in this respect. In this study a bioinformatics approach specialized in identifying lipid binding helical regions in proteins was used to obtain an Eisenberg plot. The validity of the Heliquest generated hydrophobic moment plot was checked and exemplified. This study indicates that the Eisenberg plot methodology can be transferred to another hydrophobicity scale and renders a user-friendly approach which can be utilized in routine checks in protein-lipid interaction and in protein and peptide lipid binding characterization studies. A combined approach seems to be advantageous and results in a powerful tool in the search of helical lipid-binding regions in proteins and peptides. The strength and limitations of the Eisenberg plot approach itself are discussed as well. The presented approach not only leads to a better understanding of the nature of the protein-lipid interactions but also provides a user-friendly tool for the search of lipid-binding regions in proteins and peptides.

Use of the Operon Structure of the C. elegans Genome as a Tool to Identify Functionally Related Proteins

Directory of Open Access Journals (Sweden)

Silvia Dossena

2013-12-01

Full Text Available One of the most pressing challenges in the post genomic era is the identification and characterization of protein-protein interactions (PPIs, as these are essential in understanding the cellular physiology of health and disease. Experimental techniques suitable for characterizing PPIs (X-ray crystallography or nuclear magnetic resonance spectroscopy, among others are usually laborious, time-consuming and often difficult to apply to membrane proteins, and therefore require accurate prediction of the candidate interacting partners. High-throughput experimental methods (yeast two-hybrid and affinity purification succumb to the same shortcomings, and can also lead to high rates of false positive and negative results. Therefore, reliable tools for predicting PPIs are needed. The use of the operon structure in the eukaryote Caenorhabditis elegans genome is a valuable, though underserved, tool for identifying physically or functionally interacting proteins. Based on the concept that genes organized in the same operon may encode physically or functionally related proteins, this algorithm is easy to be applied and, importantly, gives a limited number of candidate partners of a given protein, allowing for focused experimental verification. Moreover, this approach can be successfully used to predict PPIs in the human system, including those of membrane proteins.

Exploring the Stakeholders Salience for the adoption the Principles and Tools of Cleaner Production in Brazil Companies

Directory of Open Access Journals (Sweden)

Geraldo Cardoso Oliveira Neto

2015-09-01

Full Text Available Objective – The key objective of this paper is to show the primary environmental influences exerted by the government, economic agents and society on companies for the implementation of the principles and tools of cleaner production (CP, and the attributes (power, legitimacy and urgency used by stakeholders to coerce companies into adopting these principles. Design/methodology/approach – The research method employed was the application of an exploratory survey in 102 Brazilian companies and the multi-varied evaluation of data by means of multiple correspondent analysis. Findings – The study shows that some principles of CP are little used by companies in Brazil. Concerning the influences on the adoption of CP, the government, economic agents and society are singled out as the important influencers. The government influence is manifest through the adoption of environmental regulating measures (power in conjunction with sincere actions in environmental education (influence. The economic agents possess the power, legitimacy and urgency to influence the adoption of CP. Society’s influences are less relevant, in that Brazilian society has much less awareness of sustainable production and consumption as compared to other countries. Practical implications – This study shows that it is vital that Brazilian society learns more about sustainable production, because a society with no environmental conscience is a society with little means to demand the implementation of CP. Originality/value – The results of the study represent an important theoretical contribution in that, at present, there is little literature on the relationship between stakeholders and Cleaner Production. This is the first study in Brazil to address the subject.

Testing tool for software concerning nuclear power plant safety

International Nuclear Information System (INIS)

Boulc'h, J.; Le Meur, M.; Collart, J.M.; Segalard, J.; Uberschlag, J.

1984-11-01

In the present case, softwares to be analyzed are all written in assembler language. This paper presents the study and the realization of a tool to analyze softwares which have an important role for nuclear reactor protection and sauvegarde: principles of the tool design, working principle, realization and evolution of dynamic analyze tool [fr

MP3: a software tool for the prediction of pathogenic proteins in genomic and metagenomic data.

Science.gov (United States)

Gupta, Ankit; Kapil, Rohan; Dhakan, Darshan B; Sharma, Vineet K

2014-01-01

The identification of virulent proteins in any de-novo sequenced genome is useful in estimating its pathogenic ability and understanding the mechanism of pathogenesis. Similarly, the identification of such proteins could be valuable in comparing the metagenome of healthy and diseased individuals and estimating the proportion of pathogenic species. However, the common challenge in both the above tasks is the identification of virulent proteins since a significant proportion of genomic and metagenomic proteins are novel and yet unannotated. The currently available tools which carry out the identification of virulent proteins provide limited accuracy and cannot be used on large datasets. Therefore, we have developed an MP3 standalone tool and web server for the prediction of pathogenic proteins in both genomic and metagenomic datasets. MP3 is developed using an integrated Support Vector Machine (SVM) and Hidden Markov Model (HMM) approach to carry out highly fast, sensitive and accurate prediction of pathogenic proteins. It displayed Sensitivity, Specificity, MCC and accuracy values of 92%, 100%, 0.92 and 96%, respectively, on blind dataset constructed using complete proteins. On the two metagenomic blind datasets (Blind A: 51-100 amino acids and Blind B: 30-50 amino acids), it displayed Sensitivity, Specificity, MCC and accuracy values of 82.39%, 97.86%, 0.80 and 89.32% for Blind A and 71.60%, 94.48%, 0.67 and 81.86% for Blind B, respectively. In addition, the performance of MP3 was validated on selected bacterial genomic and real metagenomic datasets. To our knowledge, MP3 is the only program that specializes in fast and accurate identification of partial pathogenic proteins predicted from short (100-150 bp) metagenomic reads and also performs exceptionally well on complete protein sequences. MP3 is publicly available at http://metagenomics.iiserb.ac.in/mp3/index.php.

EcoPrinciples Connect: A Pilot Project Matching Ecological Principles with Available Data to Promote Ecosystem-Based Management

Science.gov (United States)

Martone, R. G.; Erickson, A.; Mach, M.; Hale, T.; McGregor, A.; Prahler, E. E.; Foley, M.; Caldwell, M.; Hartge, E. H.

2016-12-01

Ocean and coastal practitioners work within existing financial constraints, jurisdictions, and legislative authorities to manage coastal and marine resources while seeking to promote and maintain a healthy and productive coastal economy. Fulfilling this mandate necessitates incorporation of best available science, including ecosystem-based management (EBM) into coastal and ocean management decisions. To do this, many agencies seek ways to apply lessons from ecological theory into their decision processes. However, making direct connections between science and management can be challenging, in part because there is no process for linking ecological principles (e.g., maintaining species diversity, habitat diversity, connectivity and populations of key species) with available data. Here we explore how incorporating emerging data and methods into resource management at a local scale can improve the overall health of our coastal and marine ecosystems. We introduce a new web-based interface, EcoPrinciples Connect, that links marine managers to scientific and geospatial information through the lens of these ecological principles, ultimately helping managers become more efficient, more consistent, and advance the integration of EBM. The EcoPrinciples Connect tool grew directly out of needs identified in response to a Center for Ocean Solutions reference guide, Incorporating Ecological Principles into California Ocean and Coastal Management: Examples from Practice. Here we illustrate how we have worked to translate the information in this guide into a co-developed, user-centric tool for agency staff. Specifically, we present a pilot project where we match publicly available data to the ecological principles for the California San Francisco Bay Conservation and Development Commission. We will share early lessons learned from pilot development and highlight opportunities for future transferability to an expanded group of practitioners.

Solubilization of myofibrillar proteins in water or low ionic strength media: Classical techniques, basic principles, and novel functionalities.

Science.gov (United States)

Chen, Xing; Tume, Ron K; Xu, Xinglian; Zhou, Guanghong

2017-10-13

The qualitative characteristics of meat products are closely related to the functionality of muscle proteins. Myofibrillar proteins (MPs), comprising approximately 50% of total muscle proteins, are generally considered to be insoluble in solutions of low ionic strength ( 0.3 M) for solubilization. These soluble proteins are the ones which determine many functional properties of meat products, including emulsification and thermal gelation. In order to increase the utilization of meat and meat products, many studies have investigated the solubilization of MPs in water or low ionic strength media and determining their functionality. However, there still remains a lack of systematic information on the functional properties of MPs solubilized in this manner. Hence, this review will explore some typical techniques that have been used. The main procedures used for their solubilization, the fundamental principles and their functionalities in water (low ionic strength medium) are comprehensively discussed. In addition, advantages and disadvantages of each technique are summarized. Finally, future considerations are presented to facilitate progress in this new area and to enable water soluble muscle MPs to be utilized as novel meat ingredients in the food industry.

A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

Directory of Open Access Journals (Sweden)

Kampf Caroline

2012-09-01

Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

MODexplorer: an integrated tool for exploring protein sequence, structure and function relationships.

KAUST Repository

Kosinski, Jan; Barbato, Alessandro; Tramontano, Anna

2013-01-01

SUMMARY: MODexplorer is an integrated tool aimed at exploring the sequence, structural and functional diversity in protein families useful in homology modeling and in analyzing protein families in general. It takes as input either the sequence or the structure of a protein and provides alignments with its homologs along with a variety of structural and functional annotations through an interactive interface. The annotations include sequence conservation, similarity scores, ligand-, DNA- and RNA-binding sites, secondary structure, disorder, crystallographic structure resolution and quality scores of models implied by the alignments to the homologs of known structure. MODexplorer can be used to analyze sequence and structural conservation among the structures of similar proteins, to find structures of homologs solved in different conformational state or with different ligands and to transfer functional annotations. Furthermore, if the structure of the query is not known, MODexplorer can be used to select the modeling templates taking all this information into account and to build a comparative model. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://modorama.biocomputing.it/modexplorer. Website implemented in HTML and JavaScript with all major browsers supported. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MODexplorer: an integrated tool for exploring protein sequence, structure and function relationships.

KAUST Repository

Kosinski, Jan

2013-02-08

SUMMARY: MODexplorer is an integrated tool aimed at exploring the sequence, structural and functional diversity in protein families useful in homology modeling and in analyzing protein families in general. It takes as input either the sequence or the structure of a protein and provides alignments with its homologs along with a variety of structural and functional annotations through an interactive interface. The annotations include sequence conservation, similarity scores, ligand-, DNA- and RNA-binding sites, secondary structure, disorder, crystallographic structure resolution and quality scores of models implied by the alignments to the homologs of known structure. MODexplorer can be used to analyze sequence and structural conservation among the structures of similar proteins, to find structures of homologs solved in different conformational state or with different ligands and to transfer functional annotations. Furthermore, if the structure of the query is not known, MODexplorer can be used to select the modeling templates taking all this information into account and to build a comparative model. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://modorama.biocomputing.it/modexplorer. Website implemented in HTML and JavaScript with all major browsers supported. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

DIDACTIC PRINCIPLES AND PSYCHOLOGICAL CHARACTERISTICS IN DEFINITION OF QUALITY OF SOFTWARE TOOLS FOR EDUCATIONAL PURPOSE IN THE GENERAL EDUCATIONAL ENVIRONMENT OF UKRAINE

Directory of Open Access Journals (Sweden)

Maryna V. Pirko

2011-02-01

Full Text Available The fundamental feature of economy of postindustrial society is the knowledge that represents the basic source of competitive advantage. In the article the circle of didactic, psychological indicators in researches of problems of achievement of a high degree of quality of education and educational services is considered and described. The attention is paid to pedagogical requirements of the given period which are a standard substantiation in orientations for quality estimation of software tools for educational purpose of the general educational environment in Ukraine. The scheme of internal model of maintenance of quality of software tools for educational purpose is considered, the aspects integrated by internal model of quality of software for educational purpose are listed. The article describes the directions of researches in the conditions of formation of the global international educational environment and uniform information space of  education system taking into account the growth of availability of educational services. It is specified the main principles in the organization of pedagogical software tools.

VASCo: computation and visualization of annotated protein surface contacts

Directory of Open Access Journals (Sweden)

Thallinger Gerhard G

2009-01-01

Full Text Available Abstract Background Structural data from crystallographic analyses contain a vast amount of information on protein-protein contacts. Knowledge on protein-protein interactions is essential for understanding many processes in living cells. The methods to investigate these interactions range from genetics to biophysics, crystallography, bioinformatics and computer modeling. Also crystal contact information can be useful to understand biologically relevant protein oligomerisation as they rely in principle on the same physico-chemical interaction forces. Visualization of crystal and biological contact data including different surface properties can help to analyse protein-protein interactions. Results VASCo is a program package for the calculation of protein surface properties and the visualization of annotated surfaces. Special emphasis is laid on protein-protein interactions, which are calculated based on surface point distances. The same approach is used to compare surfaces of two aligned molecules. Molecular properties such as electrostatic potential or hydrophobicity are mapped onto these surface points. Molecular surfaces and the corresponding properties are calculated using well established programs integrated into the package, as well as using custom developed programs. The modular package can easily be extended to include new properties for annotation. The output of the program is most conveniently displayed in PyMOL using a custom-made plug-in. Conclusion VASCo supplements other available protein contact visualisation tools and provides additional information on biological interactions as well as on crystal contacts. The tool provides a unique feature to compare surfaces of two aligned molecules based on point distances and thereby facilitates the visualization and analysis of surface differences.

Proteomic tools for environmental microbiology--a roadmap from sample preparation to protein identification and quantification.

Science.gov (United States)

Wöhlbrand, Lars; Trautwein, Kathleen; Rabus, Ralf

2013-10-01

The steadily increasing amount of (meta-)genomic sequence information of diverse organisms and habitats has a strong impact on research in microbial physiology and ecology. In-depth functional understanding of metabolic processes and overall physiological adaptation to environmental changes, however, requires application of proteomics, as the context specific proteome constitutes the true functional output of a cell. Considering the enormous structural and functional diversity of proteins, only rational combinations of various analytical approaches allow a holistic view on the overall state of the cell. Within the past decade, proteomic methods became increasingly accessible to microbiologists mainly due to the robustness of analytical methods (e.g. 2DE), and affordability of mass spectrometers and their relative ease of use. This review provides an overview on the complex portfolio of state-of-the-art proteomics and highlights the basic principles of key methods, ranging from sample preparation of laboratory or environmental samples, via protein/peptide separation (gel-based or gel-free) and different types of mass spectrometric protein/peptide analyses, to protein identification and abundance determination. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mutagenesis Objective Search and Selection Tool (MOSST: an algorithm to predict structure-function related mutations in proteins

Directory of Open Access Journals (Sweden)

Asenjo Juan A

2011-04-01

's primary sequence into a group of functionally non-disruptive amino acids and a second group of functionally deleterious amino acids. Conclusions With this approach, not only conserved amino acid positions in a protein family can be labeled as functionally relevant, but also non-conserved amino acid positions can be identified to have a physicochemically meaningful functional effect. These results become a discriminative tool in the selection and elaboration of rational mutagenesis strategies for the protein. They can also be used to predict if a given nsSNP, identified, for instance, in a genomic-scale analysis, can have a functional implication for a particular protein and which nsSNPs are most likely to be functionally silent for a protein. This analytical tool could be used to rapidly and automatically discard any irrelevant nsSNP and guide the research focus toward functionally significant mutations. Based on preliminary results and applications, this technique shows promising performance as a valuable bioinformatics tool to aid in the development of new protein variants and in the understanding of function-structure relationships in proteins.

Infrared and Raman Spectroscopy Principles and Spectral Interpretation

CERN Document Server

Larkin, Peter

2011-01-01

Infrared and Raman Spectroscopy: Principles and Spectral Interpretation explains the background, core principles and tests the readers understanding of the important techniques of Infrared and Raman Spectroscopy. These techniques are used by chemists, environmental scientists, forensic scientists etc to identify unknown chemicals. In the case of an organic chemist these tools are part of an armory of techniques that enable them to conclusively prove what compound they have made, which is essential for those being used in medical applications. The book reviews basic principles, instrumentation

A bootstrap invariance principle for highly nonstationary long memory processes

OpenAIRE

Kapetanios, George

2004-01-01

This paper presents an invariance principle for highly nonstationary long memory processes, defined as processes with long memory parameter lying in (1, 1.5). This principle provides the tools for showing asymptotic validity of the bootstrap in the context of such processes.

Exploration of the dynamic properties of protein complexes predicted from spatially constrained protein-protein interaction networks.

Directory of Open Access Journals (Sweden)

Eric A Yen

2014-05-01

Full Text Available Protein complexes are not static, but rather highly dynamic with subunits that undergo 1-dimensional diffusion with respect to each other. Interactions within protein complexes are modulated through regulatory inputs that alter interactions and introduce new components and deplete existing components through exchange. While it is clear that the structure and function of any given protein complex is coupled to its dynamical properties, it remains a challenge to predict the possible conformations that complexes can adopt. Protein-fragment Complementation Assays detect physical interactions between protein pairs constrained to ≤8 nm from each other in living cells. This method has been used to build networks composed of 1000s of pair-wise interactions. Significantly, these networks contain a wealth of dynamic information, as the assay is fully reversible and the proteins are expressed in their natural context. In this study, we describe a method that extracts this valuable information in the form of predicted conformations, allowing the user to explore the conformational landscape, to search for structures that correlate with an activity state, and estimate the abundance of conformations in the living cell. The generator is based on a Markov Chain Monte Carlo simulation that uses the interaction dataset as input and is constrained by the physical resolution of the assay. We applied this method to an 18-member protein complex composed of the seven core proteins of the budding yeast Arp2/3 complex and 11 associated regulators and effector proteins. We generated 20,480 output structures and identified conformational states using principle component analysis. We interrogated the conformation landscape and found evidence of symmetry breaking, a mixture of likely active and inactive conformational states and dynamic exchange of the core protein Arc15 between core and regulatory components. Our method provides a novel tool for prediction and

“Biotecnological War” - A Conceptual And Perceptual Assessment Tool For Teaching Biotechnology And Protein Chemistry For Undergraduate Students In Biological Sciences.

OpenAIRE

C. R. C. Cruz et al.

2017-01-01

"Biotecnological War" board game, a conceptual and perceptual assessment tool for biotechnology and protein chemistry teaching for undergraduate students in biological sciences and related areas. It is a proposal initially conceived as an alternative complementary tool for biochemistry teaching of proteins and peptides, challenging students, aiming to review concepts transmitted in classroom, stimulating diverse student’s abilities, such as their creativity, competitiveness and resource manag...

Teaching geometrical principles to design students

Directory of Open Access Journals (Sweden)

Christoph Bartneck

2009-12-01

Full Text Available We propose a new method of teaching the principles of geometry to design students. The students focus on a field of design in which geometry is the design: tessellation. We review different approaches to geometry and the field of tessellation before we discuss the setup of the course. Instead of employing 2D drawing tools, such as Adobe Illustrator, the students define their tessellation in mathematical formulas, using the Mathematica software. This procedure enables them to understand the mathematical principles on which graphical tools, such as Illustrator are built upon. But we do not stop at a digital representation of their tessellation design we continue to cut their tessellations in Perspex. It moves the abstract concepts of math into the real world, so that the students can experience them directly, which provides a tremendous reward to the students.

RESCUE: An artificial neural network tool for the NMR spectral assignment of proteins

International Nuclear Information System (INIS)

Pons, J.L.; Delsuc, M.A.

1999-01-01

The assignment of the 1 H spectrum of a protein or a polypeptide is the prerequisite for advanced NMR studies. We present here an assignment tool based on the artificial neural network technology, which determines the type of the amino acid from the chemical shift values observed in the 1 H spectrum. Two artificial neural networks have been trained and extensively tested against a non-redundant subset of the BMRB chemical shift data bank [Seavey, B.R. et al. (1991) J. Biomol. NMR, 1, 217-236]. The most promising of the two accomplishes the analysis in two steps, grouping related amino acids together. It presents a mean rate of success above 80% on the test set. The second network tested separates down to the single amino acid; it presents a mean rate of success of 63%. This tool has been used to assist the manual assignment of peptides and proteins and can also be used as a block in an automated approach to assignment. The program has been called RESCUE and is made publicly available at the following URL: http://www.infobiosud.univ-montp1.fr/rescue

Limitations of polyethylene glycol-induced precipitation as predictive tool for protein solubility during formulation development.

Science.gov (United States)

Hofmann, Melanie; Winzer, Matthias; Weber, Christian; Gieseler, Henning

2018-05-01

Polyethylene glycol (PEG)-induced protein precipitation is often used to extrapolate apparent protein solubility at specific formulation compositions. The procedure was used for several fields of application such as protein crystal growth but also protein formulation development. Nevertheless, most studies focused on applicability in protein crystal growth. In contrast, this study focuses on applicability of PEG-induced precipitation during high-concentration protein formulation development. In this study, solubility of three different model proteins was investigated over a broad range of pH. Solubility values predicted by PEG-induced precipitation were compared to real solubility behaviour determined by either turbidity or content measurements. Predicted solubility by PEG-induced precipitation was confirmed for an Fc fusion protein and a monoclonal antibody. In contrast, PEG-induced precipitation failed to predict solubility of a single-domain antibody construct. Applicability of PEG-induced precipitation as indicator of protein solubility during formulation development was found to be not valid for one of three model molecules. Under certain conditions, PEG-induced protein precipitation is not valid for prediction of real protein solubility behaviour. The procedure should be used carefully as tool for formulation development, and the results obtained should be validated by additional investigations. © 2017 Royal Pharmaceutical Society.

Principles for enabling deep secondary design

DEFF Research Database (Denmark)

Pries-Heje, Jan; Hansen, Magnus Rotvit Perlt

2017-01-01

design by analyzing two cases where secondary designers fundamentally change functionality, content and technology complexity level. The first case redesigns a decision model for agile development in an insurance company; the second creates a contingency model for choosing project management tools...... and techniques in a hospital. Our analysis of the two cases leads to the identification of four principles of design implementation that primary designers can apply to enable secondary design and four corresponding design implementation principles that secondary designers themselves need to apply....

Conditional protein splicing: a new tool to control protein structure and function in vitro and in vivo.

Science.gov (United States)

Mootz, Henning D; Blum, Elyse S; Tyszkiewicz, Amy B; Muir, Tom W

2003-09-03

Protein splicing is a naturally occurring process in which an intervening intein domain excises itself out of a precursor polypeptide in an autocatalytic fashion with concomitant linkage of the two flanking extein sequences by a native peptide bond. We have recently reported an engineered split VMA intein whose splicing activity in trans between two polypeptides can be triggered by the small molecule rapamycin. In this report, we show that this conditional protein splicing (CPS) system can be used in mammalian cells. Two model constructs harboring maltose-binding protein (MBP) and a His-tag as exteins were expressed from a constitutive promoter after transient transfection. The splicing product MBP-His was detected by Western blotting and immunoprecipitation in cells treated with rapamycin or a nontoxic analogue thereof. No background splicing in the absence of the small-molecule inducer was observed over a 24-h time course. Product formation could be detected within 10 min of addition of rapamycin, indicating the advantage of the posttranslational nature of CPS for quick responses. The level of protein splicing was dose dependent and could be competitively attenuated with the small molecule ascomycin. In related studies, the geometric flexibility of the CPS components was investigated with a series of purified proteins. The FKBP and FRB domains, which are dimerized by rapamycin and thereby induce the reconstitution of the split intein, were fused to the extein sequences of the split intein halves. CPS was still triggered by rapamycin when FKBP and FRB occupied one or both of the extein positions. This finding suggests yet further applications of CPS in the area of proteomics. In summary, CPS holds great promise to become a powerful new tool to control protein structure and function in vitro and in living cells.

Variational principles for Ginzburg-Landau equation by He's semi-inverse method

International Nuclear Information System (INIS)

Liu, W.Y.; Yu, Y.J.; Chen, L.D.

2007-01-01

Via the semi-inverse method of establishing variational principles proposed by He, a generalized variational principle is established for Ginzburg-Landau equation. The present theory provides a quite straightforward tool to the search for various variational principles for physical problems. This paper aims at providing a more complete theoretical basis for applications using finite element and other direct variational methods

SpirPro: A Spirulina proteome database and web-based tools for the analysis of protein-protein interactions at the metabolic level in Spirulina (Arthrospira) platensis C1.

Science.gov (United States)

Senachak, Jittisak; Cheevadhanarak, Supapon; Hongsthong, Apiradee

2015-07-29

Spirulina (Arthrospira) platensis is the only cyanobacterium that in addition to being studied at the molecular level and subjected to gene manipulation, can also be mass cultivated in outdoor ponds for commercial use as a food supplement. Thus, encountering environmental changes, including temperature stresses, is common during the mass production of Spirulina. The use of cyanobacteria as an experimental platform, especially for photosynthetic gene manipulation in plants and bacteria, is becoming increasingly important. Understanding the mechanisms and protein-protein interaction networks that underlie low- and high-temperature responses is relevant to Spirulina mass production. To accomplish this goal, high-throughput techniques such as OMICs analyses are used. Thus, large datasets must be collected, managed and subjected to information extraction. Therefore, databases including (i) proteomic analysis and protein-protein interaction (PPI) data and (ii) domain/motif visualization tools are required for potential use in temperature response models for plant chloroplasts and photosynthetic bacteria. A web-based repository was developed including an embedded database, SpirPro, and tools for network visualization. Proteome data were analyzed integrated with protein-protein interactions and/or metabolic pathways from KEGG. The repository provides various information, ranging from raw data (2D-gel images) to associated results, such as data from interaction and/or pathway analyses. This integration allows in silico analyses of protein-protein interactions affected at the metabolic level and, particularly, analyses of interactions between and within the affected metabolic pathways under temperature stresses for comparative proteomic analysis. The developed tool, which is coded in HTML with CSS/JavaScript and depicted in Scalable Vector Graphics (SVG), is designed for interactive analysis and exploration of the constructed network. SpirPro is publicly available on the web

FUNCTIONAL DETERMINATION AND COMPLEMENTARITY AS PRINCIPLES OF ELECTRONIC TEXTBOOKS DEVELOPMENT

Directory of Open Access Journals (Sweden)

Olena Yu. Balalaieva

2015-04-01

Full Text Available The article deals with specific principles for creating and using e-learning tools presented in the modern pedagogical literature. The author has analyzed which of these principles could be applied to electronic textbooks (in particular, the validity of such principles as individualization, interactivity, structurization was proved. Based on critical analysis of psychological and pedagogical sources the mechanical spread of completeness (integrity and continuity of the didactic cycle principle to all electronic educational editions has been stated. The invalidation of absolute and imperative application of this principle to the electronic textbooks was proved. New specific principles of electronic textbooks development — functional determination and complementarity – are proposed and theoretically grounded.

Evolutionary reprograming of protein-protein interaction specificity.

Science.gov (United States)

Akiva, Eyal; Babbitt, Patricia C

2015-10-22

Using mutation libraries and deep sequencing, Aakre et al. study the evolution of protein-protein interactions using a toxin-antitoxin model. The results indicate probable trajectories via "intermediate" proteins that are promiscuous, thus avoiding transitions via non-interactions. These results extend observations about other biological interactions and enzyme evolution, suggesting broadly general principles. Copyright © 2015 Elsevier Inc. All rights reserved.

Detecting Repetitions and Periodicities in Proteins by Tiling the Structural Space

OpenAIRE

Parra, R. Gonzalo; Espada, Rocío; Sánchez, Ignacio E.; Sippl, Manfred J.; Ferreiro, Diego U.

2013-01-01

The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy landscape theory indicates that it is much easier to find sequences that satisfy the “Principle of Minimal Frustration” when the folded structure is symmetric (Wolynes, P. G. Symmetry and the Energy Landscapes of Biomolecules. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14249–14255). Similarly, repeats and structural mosaics may be fundamentally related to landscape...

High-Resolution RNA Maps Suggest Common Principles of Splicing and Polyadenylation Regulation by TDP-43

Directory of Open Access Journals (Sweden)

Gregor Rot

2017-05-01

Full Text Available Many RNA-binding proteins (RBPs regulate both alternative exons and poly(A site selection. To understand their regulatory principles, we developed expressRNA, a web platform encompassing computational tools for integration of iCLIP and RNA motif analyses with RNA-seq and 3′ mRNA sequencing. This reveals at nucleotide resolution the “RNA maps” describing how the RNA binding positions of RBPs relate to their regulatory functions. We use this approach to examine how TDP-43, an RBP involved in several neurodegenerative diseases, binds around its regulated poly(A sites. Binding close to the poly(A site generally represses, whereas binding further downstream enhances use of the site, which is similar to TDP-43 binding around regulated exons. Our RNAmotifs2 software also identifies sequence motifs that cluster together with the binding motifs of TDP-43. We conclude that TDP-43 directly regulates diverse types of pre-mRNA processing according to common position-dependent principles.

Effective Educational Videos: Principles and Guidelines for Maximizing Student Learning from Video Content

Science.gov (United States)

Brame, Cynthia J.

2016-01-01

Educational videos have become an important part of higher education, providing an important content-delivery tool in many flipped, blended, and online classes. Effective use of video as an educational tool is enhanced when instructors consider three elements: how to manage cognitive load of the video; how to maximize student engagement with the video; and how to promote active learning from the video. This essay reviews literature relevant to each of these principles and suggests practical ways instructors can use these principles when using video as an educational tool. PMID:27789532

MDcons: Intermolecular contact maps as a tool to analyze the interface of protein complexes from molecular dynamics trajectories

KAUST Repository

Abdel-Azeim, Safwat

2014-05-06

Background: Molecular Dynamics ( MD) simulations of protein complexes suffer from the lack of specific tools in the analysis step. Analyses of MD trajectories of protein complexes indeed generally rely on classical measures, such as the RMSD, RMSF and gyration radius, conceived and developed for single macromolecules. As a matter of fact, instead, researchers engaged in simulating the dynamics of a protein complex are mainly interested in characterizing the conservation/variation of its biological interface. Results: On these bases, herein we propose a novel approach to the analysis of MD trajectories or other conformational ensembles of protein complexes, MDcons, which uses the conservation of inter-residue contacts at the interface as a measure of the similarity between different snapshots. A "consensus contact map" is also provided, where the conservation of the different contacts is drawn in a grey scale. Finally, the interface area of the complex is monitored during the simulations. To show its utility, we used this novel approach to study two protein-protein complexes with interfaces of comparable size and both dominated by hydrophilic interactions, but having binding affinities at the extremes of the experimental range. MDcons is demonstrated to be extremely useful to analyse the MD trajectories of the investigated complexes, adding important insight into the dynamic behavior of their biological interface. Conclusions: MDcons specifically allows the user to highlight and characterize the dynamics of the interface in protein complexes and can thus be used as a complementary tool for the analysis of MD simulations of both experimental and predicted structures of protein complexes.

FeatureMap3D - a tool to map protein features and sequence conservation onto homologous structures in the PDB

DEFF Research Database (Denmark)

Wernersson, Rasmus; Rapacki, Krzysztof; Stærfeldt, Hans Henrik

2006-01-01

FeatureMap3D is a web-based tool that maps protein features onto 3D structures. The user provides sequences annotated with any feature of interest, such as post-translational modifications, protease cleavage sites or exonic structure and FeatureMap3D will then search the Protein Data Bank (PDB) f...

Elucidating the design principles of photosynthetic electron-transfer proteins by site-directed spin labeling EPR spectroscopy.

Science.gov (United States)

Ishara Silva, K; Jagannathan, Bharat; Golbeck, John H; Lakshmi, K V

2016-05-01

Site-directed spin labeling electron paramagnetic resonance (SDSL EPR) spectroscopy is a powerful tool to determine solvent accessibility, side-chain dynamics, and inter-spin distances at specific sites in biological macromolecules. This information provides important insights into the structure and dynamics of both natural and designed proteins and protein complexes. Here, we discuss the application of SDSL EPR spectroscopy in probing the charge-transfer cofactors in photosynthetic reaction centers (RC) such as photosystem I (PSI) and the bacterial reaction center (bRC). Photosynthetic RCs are large multi-subunit proteins (molecular weight≥300 kDa) that perform light-driven charge transfer reactions in photosynthesis. These reactions are carried out by cofactors that are paramagnetic in one of their oxidation states. This renders the RCs unsuitable for conventional nuclear magnetic resonance spectroscopy investigations. However, the presence of native paramagnetic centers and the ability to covalently attach site-directed spin labels in RCs makes them ideally suited for the application of SDSL EPR spectroscopy. The paramagnetic centers serve as probes of conformational changes, dynamics of subunit assembly, and the relative motion of cofactors and peptide subunits. In this review, we describe novel applications of SDSL EPR spectroscopy for elucidating the effects of local structure and dynamics on the electron-transfer cofactors of photosynthetic RCs. Because SDSL EPR Spectroscopy is uniquely suited to provide dynamic information on protein motion, it is a particularly useful method in the engineering and analysis of designed electron transfer proteins and protein networks. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. Copyright © 2016. Published by Elsevier B.V.

Cosmological principles. II. Physical principles

International Nuclear Information System (INIS)

Harrison, E.R.

1974-01-01

The discussion of cosmological principle covers the uniformity principle of the laws of physics, the gravitation and cognizability principles, and the Dirac creation, chaos, and bootstrap principles. (U.S.)

Pierced Lasso Proteins

Science.gov (United States)

Jennings, Patricia

Entanglement and knots are naturally occurring, where, in the microscopic world, knots in DNA and homopolymers are well characterized. The most complex knots are observed in proteins which are harder to investigate, as proteins are heteropolymers composed of a combination of 20 different amino acids with different individual biophysical properties. As new-knotted topologies and new proteins containing knots continue to be discovered and characterized, the investigation of knots in proteins has gained intense interest. Thus far, the principle focus has been on the evolutionary origin of tying a knot, with questions of how a protein chain `self-ties' into a knot, what the mechanism(s) are that contribute to threading, and the biological relevance and functional implication of a knotted topology in vivo gaining the most insight. Efforts to study the fully untied and unfolded chain indicate that the knot is highly stable, remaining intact in the unfolded state orders of magnitude longer than first anticipated. The persistence of ``stable'' knots in the unfolded state, together with the challenge of defining an unfolded and untied chain from an unfolded and knotted chain, complicates the study of fully untied protein in vitro. Our discovery of a new class of knotted proteins, the Pierced Lassos (PL) loop topology, simplifies the knotting approach. While PLs are not easily recognizable by the naked eye, they have now been identified in many proteins in the PDB through the use of computation tools. PL topologies are diverse proteins found in all kingdoms of life, performing a large variety of biological responses such as cell signaling, immune responses, transporters and inhibitors (http://lassoprot.cent.uw.edu.pl/). Many of these PL topologies are secreted proteins, extracellular proteins, as well as, redox sensors, enzymes and metal and co-factor binding proteins; all of which provide a favorable environment for the formation of the disulphide bridge. In the PL

Physical acoustics v.8 principles and methods

CERN Document Server

Mason, Warren P

1971-01-01

Physical Acoustics: Principles and Methods, Volume VIII discusses a number of themes on physical acoustics that are divided into seven chapters. Chapter 1 describes the principles and applications of a tool for investigating phonons in dielectric crystals, the spin phonon spectrometer. The next chapter discusses the use of ultrasound in investigating Landau quantum oscillations in the presence of a magnetic field and their relation to the strain dependence of the Fermi surface of metals. The third chapter focuses on the ultrasonic measurements that are made by pulsing methods with velo

The equivalence principle in a quantum world

DEFF Research Database (Denmark)

Bjerrum-Bohr, N. Emil J.; Donoghue, John F.; El-Menoufi, Basem Kamal

2015-01-01

the energy is small, we now have the tools to address this conflict explicitly. Despite the violation of some classical concepts, the EP continues to provide the core of the quantum gravity framework through the symmetry - general coordinate invariance - that is used to organize the effective field theory......We show how modern methods can be applied to quantum gravity at low energy. We test how quantum corrections challenge the classical framework behind the equivalence principle (EP), for instance through introduction of nonlocality from quantum physics, embodied in the uncertainty principle. When...

The Princeton Protein Orthology Database (P-POD): a comparative genomics analysis tool for biologists.

OpenAIRE

Sven Heinicke; Michael S Livstone; Charles Lu; Rose Oughtred; Fan Kang; Samuel V Angiuoli; Owen White; David Botstein; Kara Dolinski

2007-01-01

Many biological databases that provide comparative genomics information and tools are now available on the internet. While certainly quite useful, to our knowledge none of the existing databases combine results from multiple comparative genomics methods with manually curated information from the literature. Here we describe the Princeton Protein Orthology Database (P-POD, http://ortholog.princeton.edu), a user-friendly database system that allows users to find and visualize the phylogenetic r...

S-layer fusion protein as a tool functionalizing emulsomes and CurcuEmulsomes for antibody binding and targeting.

Science.gov (United States)

Ucisik, Mehmet H; Küpcü, Seta; Breitwieser, Andreas; Gelbmann, Nicola; Schuster, Bernhard; Sleytr, Uwe B

2015-04-01

Selective targeting of tumor cells by nanoparticle-based drug delivery systems is highly desirable because it maximizes the drug concentration at the desired target while simultaneously protecting the surrounding healthy tissues. Here, we show a design for smart nanocarriers based on a biomimetic approach that utilizes the building principle of virus envelope structures. Emulsomes and CurcuEmulsomes comprising a tripalmitin solid core surrounded by phospholipid layers are modified by S-layer proteins that self-assemble into a two-dimensional array to form a surface layer. One significant advantage of this nanoformulation is that it increases the solubility of the lipophilic anti-cancer agent curcumin in the CurcuEmulsomes by a factor of 2700. In order to make the emulsomes specific for IgG, the S-layer protein is fused with two protein G domains. This S-layer fusion protein preserves its recrystallization characteristics, forming an ordered surface layer (square lattice with 13 nm unit-by-unit distance). The GG domains are presented in a predicted orientation and exhibit a selective binding affinity for IgG. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

XAFS Spectroscopy : Fundamental Principles and Data Analysis

NARCIS (Netherlands)

Koningsberger, D.C.; Mojet, B.L.; Dorssen, G.E. van; Ramaker, D.E.

2000-01-01

The physical principles of XAFS spectroscopy are given at a sufficiently basic level to enable scientists working in the field of catalysis to critically evaluate articles dealing with XAFS studies on catalytic materials. The described data-analysis methods provide the basic tools for studying the

New tool for spreading proteins to the environment: Cry1Ab toxin immobilized to bioplastics.

Science.gov (United States)

Moldes, Cristina; Farinós, Gema P; de Eugenio, Laura I; García, Pedro; García, José L; Ortego, Félix; Hernández-Crespo, Pedro; Castañera, Pedro; Prieto, María A

2006-08-01

A new tool to provide an environmentally friendly way to deliver active proteins to the environment has been developed, based on the use of polyhydroxyalkanoate (PHA, bioplastic) granules. To illustrate this novel approach, a derived Cry1Ab insect-specific toxin protein was in vivo immobilized into PHA granules through the polypeptide tag BioF. The new toxin, named Fk-Bt1, was shown to be active against Sesamia nonagrioides (Lepidoptera: Noctuidae). The dose-mortality responses of the new toxin granule formulation (PFk-Bt1) and purified Cry1Ab have been compared, demonstrating the effectiveness of PFk-Bt1 and suggesting a common mode of action.

Variational principles of continuum mechanics. Vol. 1. Fundamentals

Energy Technology Data Exchange (ETDEWEB)

Berdichevsky, Victor L. [Wayne State Univ., Detroit, MI (United States). Dept. of Mechanical Engineering

2009-07-01

The book reviews the two features of the variational approach: its use as a universal tool to describe physical phenomena and as a source for qualitative and quantitative methods of studying particular problems. Berdichevsky's work differs from other books on the subject in focusing mostly on the physical origin of variational principles as well as establishing their interrelations. For example, the Gibbs principles appear as a consequence of the Einstein formula for thermodynamic fluctuations rather than as the first principles of the theory of thermodynamic equilibrium. Mathematical issues are considered as long as they shed light on the physical outcomes and/or provide a useful technique for the direct study of variational problems. In addition, a thorough account of variational principles discovered in various branches of continuum mechanics is given. In this book, the first volume, the author covers the variational principles for systems with a finite number of degrees of freedom; the variational principles of thermodynamics; the basics of continuum mechanics; the variational principles for classical models of continuum mechanics, such as elastic and plastic bodies, and ideal and viscous fluids; and direct methods of calculus of variations. (orig.)

Principles of Stellar Interferometry

CERN Document Server

Glindemann, Andreas

2011-01-01

Over the last decade, stellar interferometry has developed from a specialist tool to a mainstream observing technique, attracting scientists whose research benefits from milliarcsecond angular resolution. Stellar interferometry has become part of the astronomer’s toolbox, complementing single-telescope observations by providing unique capabilities that will advance astronomical research. This carefully written book is intended to provide a solid understanding of the principles of stellar interferometry to students starting an astronomical research project in this field or to develop instruments and to astronomers using interferometry but who are not interferometrists per se. Illustrated by excellent drawings and calculated graphs the imaging process in stellar interferometers is explained starting from first principles on light propagation and diffraction wave propagation through turbulence is described in detail using Kolmogorov statistics the impact of turbulence on the imaging process is discussed both f...

SA-Search: a web tool for protein structure mining based on a Structural Alphabet.

Science.gov (United States)

Guyon, Frédéric; Camproux, Anne-Claude; Hochez, Joëlle; Tufféry, Pierre

2004-07-01

SA-Search is a web tool that can be used to mine for protein structures and extract structural similarities. It is based on a hidden Markov model derived Structural Alphabet (SA) that allows the compression of three-dimensional (3D) protein conformations into a one-dimensional (1D) representation using a limited number of prototype conformations. Using such a representation, classical methods developed for amino acid sequences can be employed. Currently, SA-Search permits the performance of fast 3D similarity searches such as the extraction of exact words using a suffix tree approach, and the search for fuzzy words viewed as a simple 1D sequence alignment problem. SA-Search is available at http://bioserv.rpbs.jussieu.fr/cgi-bin/SA-Search.

SCOWLP: a web-based database for detailed characterization and visualization of protein interfaces

Directory of Open Access Journals (Sweden)

Schroeder Michael

2006-03-01

Full Text Available Abstract Background Currently there is a strong need for methods that help to obtain an accurate description of protein interfaces in order to be able to understand the principles that govern molecular recognition and protein function. Many of the recent efforts to computationally identify and characterize protein networks extract protein interaction information at atomic resolution from the PDB. However, they pay none or little attention to small protein ligands and solvent. They are key components and mediators of protein interactions and fundamental for a complete description of protein interfaces. Interactome profiling requires the development of computational tools to extract and analyze protein-protein, protein-ligand and detailed solvent interaction information from the PDB in an automatic and comparative fashion. Adding this information to the existing one on protein-protein interactions will allow us to better understand protein interaction networks and protein function. Description SCOWLP (Structural Characterization Of Water, Ligands and Proteins is a user-friendly and publicly accessible web-based relational database for detailed characterization and visualization of the PDB protein interfaces. The SCOWLP database includes proteins, peptidic-ligands and interface water molecules as descriptors of protein interfaces. It contains currently 74,907 protein interfaces and 2,093,976 residue-residue interactions formed by 60,664 structural units (protein domains and peptidic-ligands and their interacting solvent. The SCOWLP web-server allows detailed structural analysis and comparisons of protein interfaces at atomic level by text query of PDB codes and/or by navigating a SCOP-based tree. It includes a visualization tool to interactively display the interfaces and label interacting residues and interface solvent by atomic physicochemical properties. SCOWLP is automatically updated with every SCOP release. Conclusion SCOWLP enriches

Electrostatic similarities between protein and small molecule ligands facilitate the design of protein-protein interaction inhibitors.

Directory of Open Access Journals (Sweden)

Arnout Voet

Full Text Available One of the underlying principles in drug discovery is that a biologically active compound is complimentary in shape and molecular recognition features to its receptor. This principle infers that molecules binding to the same receptor may share some common features. Here, we have investigated whether the electrostatic similarity can be used for the discovery of small molecule protein-protein interaction inhibitors (SMPPIIs. We have developed a method that can be used to evaluate the similarity of electrostatic potentials between small molecules and known protein ligands. This method was implemented in a software called EleKit. Analyses of all available (at the time of research SMPPII structures indicate that SMPPIIs bear some similarities of electrostatic potential with the ligand proteins of the same receptor. This is especially true for the more polar SMPPIIs. Retrospective analysis of several successful SMPPIIs has shown the applicability of EleKit in the design of new SMPPIIs.

Structure Based Thermostability Prediction Models for Protein Single Point Mutations with Machine Learning Tools.

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Lei Jia

Full Text Available Thermostability issue of protein point mutations is a common occurrence in protein engineering. An application which predicts the thermostability of mutants can be helpful for guiding decision making process in protein design via mutagenesis. An in silico point mutation scanning method is frequently used to find "hot spots" in proteins for focused mutagenesis. ProTherm (http://gibk26.bio.kyutech.ac.jp/jouhou/Protherm/protherm.html is a public database that consists of thousands of protein mutants' experimentally measured thermostability. Two data sets based on two differently measured thermostability properties of protein single point mutations, namely the unfolding free energy change (ddG and melting temperature change (dTm were obtained from this database. Folding free energy change calculation from Rosetta, structural information of the point mutations as well as amino acid physical properties were obtained for building thermostability prediction models with informatics modeling tools. Five supervised machine learning methods (support vector machine, random forests, artificial neural network, naïve Bayes classifier, K nearest neighbor and partial least squares regression are used for building the prediction models. Binary and ternary classifications as well as regression models were built and evaluated. Data set redundancy and balancing, the reverse mutations technique, feature selection, and comparison to other published methods were discussed. Rosetta calculated folding free energy change ranked as the most influential features in all prediction models. Other descriptors also made significant contributions to increasing the accuracy of the prediction models.

Authoring Tools

Science.gov (United States)

Treviranus, Jutta

Authoring tools that are accessible and that enable authors to produce accessible Web content play a critical role in web accessibility. Widespread use of authoring tools that comply to the W3C Authoring Tool Accessibility Guidelines (ATAG) would ensure that even authors who are neither knowledgeable about nor particularly motivated to produce accessible content do so by default. The principles and techniques of ATAG are discussed. Some examples of accessible authoring tools are described including authoring tool content management components such as TinyMCE. Considerations for creating an accessible collaborative environment are also covered. As part of providing accessible content, the debate between system-based personal optimization and one universally accessible site configuration is presented. The issues and potential solutions to address the accessibility crisis presented by the advent of rich internet applications are outlined. This challenge must be met to ensure that a large segment of the population is able to participate in the move toward the web as a two-way communication mechanism.

The Lookahead Principle for Preference Elicitation: Experimental Results

OpenAIRE

Viappiani, Paolo; Faltings, Boi; Pu, Pearl

2006-01-01

Preference-based search is the problem of finding an item that matches best with a user's preferences. User studies show that example-based tools for preference-based search can achieve significantly higher accuracy when they are complemented with suggestions chosen to inform users about the available choices. We discuss the problem of eliciting preferences in example-based tools and present the lookahead principle for generating suggestions. We compare two different implementations of this p...

Data Mining Tools in Science Education

OpenAIRE

Premysl Zaskodny

2012-01-01

The main principle of paper is Data Mining in Science Education (DMSE) as Problem Solving. The main goal of paper is consisting in Delimitation of Complex Data Mining Tool and Partial Data Mining Tool of DMSE. The procedure of paper is consisting of Data Preprocessing in Science Education, Data Processing in Science Education, Description of Curricular Process as Complex Data Mining Tool (CP-DMSE), Description of Analytical Synthetic Modeling as Partial Data Mining Tool (ASM-DMSE) and finally...

Online Graphing Activity for Principles of Economics Courses

OpenAIRE

Oskar R. Harmon; James Lambrinos

2010-01-01

This paper describes how an online drawing program and bulletin board are used to create active learning activities for a principles of economics class. In the activity the student downloads an initial diagram that sets up a textbook principles scenario. The student uses an image-editing program to complete the diagram, so that it represents the outcome predicted in the textbook and posts it to a bulletin board. The tools for the activity: SumoPaint.com, and WikiSpaces.com; are free and avail...

Principles of Fourier analysis

CERN Document Server

Howell, Kenneth B

2001-01-01

Fourier analysis is one of the most useful and widely employed sets of tools for the engineer, the scientist, and the applied mathematician. As such, students and practitioners in these disciplines need a practical and mathematically solid introduction to its principles. They need straightforward verifications of its results and formulas, and they need clear indications of the limitations of those results and formulas.Principles of Fourier Analysis furnishes all this and more. It provides a comprehensive overview of the mathematical theory of Fourier analysis, including the development of Fourier series, "classical" Fourier transforms, generalized Fourier transforms and analysis, and the discrete theory. Much of the author''s development is strikingly different from typical presentations. His approach to defining the classical Fourier transform results in a much cleaner, more coherent theory that leads naturally to a starting point for the generalized theory. He also introduces a new generalized theory based ...

Seven Foundational Principles of Population Health Policy.

Science.gov (United States)

Bhattacharya, Dru; Bhatt, Jay

2017-10-01

In 2016, Keyes and Galea issued 9 foundational principles of population health science and invited further deliberations by specialists to advance the field. This article presents 7 foundational principles of population health policy whose intersection with health care, public health, preventive medicine, and now population health, presents unique challenges. These principles are in response to a number of overarching questions that have arisen in over a decade of the authors' collective practice in the public and private sectors, and having taught policy within programs of medicine, law, nursing, and public health at the graduate and executive levels. The principles address an audience of practitioners and policy makers, mindful of the pressing health care challenges of our time, including: rising health-related expenditures, an aging population, workforce shortages, health disparities, and a backdrop of inequities rooted in social determinants that have not been adequately translated into formal policies or practices among the key stakeholders in population health. These principles are meant to empower stakeholders-whether it is the planner or the practitioner, the decision maker or the dedicated caregiver-and inform the development of practical tools, research, and education.

Bone protein extraction without demineralization using principles from hydroxyapatite chromatography.

Science.gov (United States)

Cleland, Timothy P; Vashishth, Deepak

2015-03-01

Historically, extraction of bone proteins has relied on the use of demineralization to better retrieve proteins from the extracellular matrix; however, demineralization can be a slow process that restricts subsequent analysis of the samples. Here, we developed a novel protein extraction method that does not use demineralization but instead uses a methodology from hydroxyapatite chromatography where high concentrations of ammonium phosphate and ammonium bicarbonate are used to extract bone proteins. We report that this method has a higher yield than those with previously published small-scale extant bone extractions, with and without demineralization. Furthermore, after digestion with trypsin and subsequent high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis, we were able to detect several extracellular matrix and vascular proteins in addition to collagen I and osteocalcin. Our new method has the potential to isolate proteins within a short period (4h) and provide information about bone proteins that may be lost during demineralization or with the use of denaturing agents. Copyright © 2014 Elsevier Inc. All rights reserved.

Protein immobilization strategies for protein biochips

NARCIS (Netherlands)

Rusmini, F.; Rusmini, Federica; Zhong, Zhiyuan; Feijen, Jan

2007-01-01

In the past few years, protein biochips have emerged as promising proteomic and diagnostic tools for obtaining information about protein functions and interactions. Important technological innovations have been made. However, considerable development is still required, especially regarding protein

Oligomeric protein structure networks: insights into protein-protein interactions

Directory of Open Access Journals (Sweden)

Brinda KV

2005-12-01

Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

The Readability of Principles of Macroeconomics Textbooks

Science.gov (United States)

Tinkler, Sarah; Woods, James

2013-01-01

The authors evaluated principles of macroeconomics textbooks for readability using Coh-Metrix, a computational linguistics tool. Additionally, they conducted an experiment on Amazon's Mechanical Turk Web site in which participants ranked the readability of text samples. There was a wide range of scores on readability indexes both among…

Design principles for cancer therapy guided by changes in complexity of protein-protein interaction networks.

Science.gov (United States)

Benzekry, Sebastian; Tuszynski, Jack A; Rietman, Edward A; Lakka Klement, Giannoula

2015-05-28

The ever-increasing expanse of online bioinformatics data is enabling new ways to, not only explore the visualization of these data, but also to apply novel mathematical methods to extract meaningful information for clinically relevant analysis of pathways and treatment decisions. One of the methods used for computing topological characteristics of a space at different spatial resolutions is persistent homology. This concept can also be applied to network theory, and more specifically to protein-protein interaction networks, where the number of rings in an individual cancer network represents a measure of complexity. We observed a linear correlation of R = -0.55 between persistent homology and 5-year survival of patients with a variety of cancers. This relationship was used to predict the proteins within a protein-protein interaction network with the most impact on cancer progression. By re-computing the persistent homology after computationally removing an individual node (protein) from the protein-protein interaction network, we were able to evaluate whether such an inhibition would lead to improvement in patient survival. The power of this approach lied in its ability to identify the effects of inhibition of multiple proteins and in the ability to expose whether the effect of a single inhibition may be amplified by inhibition of other proteins. More importantly, we illustrate specific examples of persistent homology calculations, which correctly predict the survival benefit observed effects in clinical trials using inhibitors of the identified molecular target. We propose that computational approaches such as persistent homology may be used in the future for selection of molecular therapies in clinic. The technique uses a mathematical algorithm to evaluate the node (protein) whose inhibition has the highest potential to reduce network complexity. The greater the drop in persistent homology, the greater reduction in network complexity, and thus a larger

The principle of the Fermionic projector

CERN Document Server

Finster, Felix

2006-01-01

The "principle of the fermionic projector" provides a new mathematical framework for the formulation of physical theories and is a promising approach for physics beyond the standard model. This book begins with a brief review of relativity, relativistic quantum mechanics, and classical gauge theories, emphasizing the basic physical concepts and mathematical foundations. The external field problem and Klein's paradox are discussed and then resolved by introducing the fermionic projector, a global object in space-time that generalizes the notion of the Dirac sea. At the mathematical core of the book is a precise definition of the fermionic projector and the use of methods of hyperbolic differential equations for detailed analysis. The fermionic projector makes it possible to formulate a new type of variational principle in space-time. The mathematical tools are developed for the analysis of the corresponding Euler-Lagrange equations. A particular variational principle is proposed that gives rise to an effective...

CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

Science.gov (United States)

Chovancova, Eva; Pavelka, Antonin; Benes, Petr; Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

2012-01-01

Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

Directory of Open Access Journals (Sweden)

Eva Chovancova

Full Text Available Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures

Science.gov (United States)

Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

2012-01-01

Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz. PMID:23093919

The extent of knowledge of Quick Response Manufacturing principles : an exploratory transnational study

NARCIS (Netherlands)

Godinho Filho, Moacir; Marchesini, Antonio Gilberto; Riezebos, Jan; Vandaele, Nico; Devos Ganga, Gilberto Miller

2017-01-01

The main goal of this research is to identify whether companies that have implemented the Quick Response Manufacturing (QRM) approach have full knowledge of the QRM principles or have merely applied the elements ( principles and tools) that have a close relationship with Lean Manufacturing. Based on

Profile of total protein, albumin, globulin and albumin globulin ratio in bulls

Directory of Open Access Journals (Sweden)

Ida Zahidah Irfan

2014-06-01

Full Text Available Determination of serum total protein concentration and main fractions (albumin and globulin can be used as an important diagnostic tool in clinical biochemistry. Several factors can affect the concentration of total protein, albumin, globulin and albumin globulin ratio (A/G. The aim of this study is to obtain serum protein profiles, albumin, globulin and A/G ratio based on breed, age and BCS (body condition score. Blood samples from 160 bulls were collected. Blood chemistry were analyzed by photometer principle using a commercial kit. There were significant (P<0.001 breed variation on total protein, albumin, globulin and albumin globulin ratio. Significant age differences were observed on total protein and albumin concentration (P<0.001, while globulin concentration and A/G ratio were also significant (P<0.05. Amongs groups of BCS, significant difference was verified only in the albumin concentration (P<0.05. The concentration of total proteins, albumins and globulins in the serum of the bulls are higher than standard values for cattle, while A/G ratio is lower.

High sensitive C-reactive protein-Effective tool in determining postoperative recovery in lumbar disc disease

Directory of Open Access Journals (Sweden)

Tushar Narayan Rathod

2014-01-01

Full Text Available Background: It is common in medical practice to see patients having persistent pain and radiculopathy even after undergoing discectomy surgery. Inflammatory cytokines, such as interleukins are produced at the site of disc herniation and are now considered responsible for the pain perceived by the patient. This study has used high sensitive C-reactive protein (HSCRP assay for predicting inflammation around the nerve roots on very same principle, which has used HSCRP for predicting coronary artery diseases in current clinical practice. Thus, purpose of this study is to test whether HSCRP can stand as an objective tool to predict postoperative recovery in patients undergoing lumbar discectomy. That is, to study association between preoperative HSCRP blood level and postoperative recovery with the help of modified Oswestry Back Disability Score. Materials and Methods: A study group consisting of 50 cases of established lumbar disc disease and control group of 50 normal subjects, matched with the study group. Both the study and control groups were subjected to detailed evaluation with the help of modified Oswestry Low Back Pain Scale both pre and postoperatively at 3 months, 6 months and 1-year. The preoperative blood samples were analyzed to assess the HSCRP concentration. All the cases underwent surgery over a period of 1-year by the same surgeon. Results: The level of HSCRP in the study group was between 0.050- and 0.710 mg/dL and in the control group, 0.005-0.020 mg/dL. There was highly significant positive correlation between preoperative HSCRP level and postoperative score at P 10 points, while those with HSCRP level in the range of 0.470 ± 0.163 mg/dL, showed poor recovery (score improved < 10 points. Conclusion: HSCRP will serve as a good supplementary prognostic marker for operative decision making in borderline and troublesome cases of lumbar disc disease.

Noninvasive imaging of protein-protein interactions from live cells and living subjects using bioluminescence resonance energy transfer.

Science.gov (United States)

De, Abhijit; Gambhir, Sanjiv Sam

2005-12-01

This study demonstrates a significant advancement of imaging of a distance-dependent physical process, known as the bioluminescent resonance energy transfer (BRET2) signal in living subjects, by using a cooled charge-coupled device (CCD) camera. A CCD camera-based spectral imaging strategy enables simultaneous visualization and quantitation of BRET signal from live cells and cells implanted in living mice. We used the BRET2 system, which utilizes Renilla luciferase (hRluc) protein and its substrate DeepBlueC (DBC) as an energy donor and a mutant green fluorescent protein (GFP2) as the acceptor. To accomplish this objective in this proof-of-principle study, the donor and acceptor proteins were fused to FKBP12 and FRB, respectively, which are known to interact only in the presence of the small molecule mediator rapamycin. Mammalian cells expressing these fusion constructs were imaged using a cooled-CCD camera either directly from culture dishes or by implanting them into mice. By comparing the emission photon yields in the presence and absence of rapamycin, the specific BRET signal was determined. The CCD imaging approach of BRET signal is particularly appealing due to its capacity to seamlessly bridge the gap between in vitro and in vivo studies. This work validates BRET as a powerful tool for interrogating and observing protein-protein interactions directly at limited depths in living mice.

PROCARB: A Database of Known and Modelled Carbohydrate-Binding Protein Structures with Sequence-Based Prediction Tools

Directory of Open Access Journals (Sweden)

Adeel Malik

2010-01-01

Full Text Available Understanding of the three-dimensional structures of proteins that interact with carbohydrates covalently (glycoproteins as well as noncovalently (protein-carbohydrate complexes is essential to many biological processes and plays a significant role in normal and disease-associated functions. It is important to have a central repository of knowledge available about these protein-carbohydrate complexes as well as preprocessed data of predicted structures. This can be significantly enhanced by tools de novo which can predict carbohydrate-binding sites for proteins in the absence of structure of experimentally known binding site. PROCARB is an open-access database comprising three independently working components, namely, (i Core PROCARB module, consisting of three-dimensional structures of protein-carbohydrate complexes taken from Protein Data Bank (PDB, (ii Homology Models module, consisting of manually developed three-dimensional models of N-linked and O-linked glycoproteins of unknown three-dimensional structure, and (iii CBS-Pred prediction module, consisting of web servers to predict carbohydrate-binding sites using single sequence or server-generated PSSM. Several precomputed structural and functional properties of complexes are also included in the database for quick analysis. In particular, information about function, secondary structure, solvent accessibility, hydrogen bonds and literature reference, and so forth, is included. In addition, each protein in the database is mapped to Uniprot, Pfam, PDB, and so forth.

An Integrated Framework Advancing Membrane Protein Modeling and Design.

Directory of Open Access Journals (Sweden)

Rebecca F Alford

2015-09-01

Full Text Available Membrane proteins are critical functional molecules in the human body, constituting more than 30% of open reading frames in the human genome. Unfortunately, a myriad of difficulties in overexpression and reconstitution into membrane mimetics severely limit our ability to determine their structures. Computational tools are therefore instrumental to membrane protein structure prediction, consequently increasing our understanding of membrane protein function and their role in disease. Here, we describe a general framework facilitating membrane protein modeling and design that combines the scientific principles for membrane protein modeling with the flexible software architecture of Rosetta3. This new framework, called RosettaMP, provides a general membrane representation that interfaces with scoring, conformational sampling, and mutation routines that can be easily combined to create new protocols. To demonstrate the capabilities of this implementation, we developed four proof-of-concept applications for (1 prediction of free energy changes upon mutation; (2 high-resolution structural refinement; (3 protein-protein docking; and (4 assembly of symmetric protein complexes, all in the membrane environment. Preliminary data show that these algorithms can produce meaningful scores and structures. The data also suggest needed improvements to both sampling routines and score functions. Importantly, the applications collectively demonstrate the potential of combining the flexible nature of RosettaMP with the power of Rosetta algorithms to facilitate membrane protein modeling and design.

Protein Structure Prediction by Protein Threading

Science.gov (United States)

Xu, Ying; Liu, Zhijie; Cai, Liming; Xu, Dong

The seminal work of Bowie, Lüthy, and Eisenberg (Bowie et al., 1991) on "the inverse protein folding problem" laid the foundation of protein structure prediction by protein threading. By using simple measures for fitness of different amino acid types to local structural environments defined in terms of solvent accessibility and protein secondary structure, the authors derived a simple and yet profoundly novel approach to assessing if a protein sequence fits well with a given protein structural fold. Their follow-up work (Elofsson et al., 1996; Fischer and Eisenberg, 1996; Fischer et al., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et al., 1992) on protein fold recognition led to the development of a new brand of powerful tools for protein structure prediction, which we now term "protein threading." These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many of the proteins encoded in the hundreds of genomes that have been sequenced up to now.

SVM-Fold: a tool for discriminative multi-class protein fold and superfamily recognition.

Science.gov (United States)

Melvin, Iain; Ie, Eugene; Kuang, Rui; Weston, Jason; Stafford, William Noble; Leslie, Christina

2007-05-22

Predicting a protein's structural class from its amino acid sequence is a fundamental problem in computational biology. Much recent work has focused on developing new representations for protein sequences, called string kernels, for use with support vector machine (SVM) classifiers. However, while some of these approaches exhibit state-of-the-art performance at the binary protein classification problem, i.e. discriminating between a particular protein class and all other classes, few of these studies have addressed the real problem of multi-class superfamily or fold recognition. Moreover, there are only limited software tools and systems for SVM-based protein classification available to the bioinformatics community. We present a new multi-class SVM-based protein fold and superfamily recognition system and web server called SVM-Fold, which can be found at http://svm-fold.c2b2.columbia.edu. Our system uses an efficient implementation of a state-of-the-art string kernel for sequence profiles, called the profile kernel, where the underlying feature representation is a histogram of inexact matching k-mer frequencies. We also employ a novel machine learning approach to solve the difficult multi-class problem of classifying a sequence of amino acids into one of many known protein structural classes. Binary one-vs-the-rest SVM classifiers that are trained to recognize individual structural classes yield prediction scores that are not comparable, so that standard "one-vs-all" classification fails to perform well. Moreover, SVMs for classes at different levels of the protein structural hierarchy may make useful predictions, but one-vs-all does not try to combine these multiple predictions. To deal with these problems, our method learns relative weights between one-vs-the-rest classifiers and encodes information about the protein structural hierarchy for multi-class prediction. In large-scale benchmark results based on the SCOP database, our code weighting approach

From principles to action: Applying the National Research Council's principles for effective decision support to the Federal Emergency Management Agency's watch office

Directory of Open Access Journals (Sweden)

Alison M. Meadow

2016-03-01

Full Text Available The National Research Council (NRC proposed six principles for effective decision support in its 2009 report Informing Decisions in a Changing Climate. We structured a collaborative project between the Federal Emergency Management Agency Region R9 (FEMA R9, the Western Region Headquarters of the National Weather Service (WR-NWS, and the Climate Assessment of the Southwest (CLIMAS at the University of Arizona around the application of the NRC principles. The goal of the project was to provide FEMA R9's Watch Office with climate information scaled to their temporal and spatial interests to aid them in assessing the potential risk of flood disasters. We found that we needed specific strategies and activities in order to apply the principles effectively. By using a set of established collaborative research approaches we were better able to assess FEMA R9's information needs and WR-NWS's capacity to meet those needs. Despite our diligent planning of engagement strategies, we still encountered some barriers to transitioning our decision support tool from research to operations. This paper describes our methods for planning and executing a three-party collaborative effort to provide climate services, the decision support tool developed through this process, and the lessons we will take from this deliberate collaborative process to our future work and implications of the NRC principles for the broader field of climate services. Keywords: Climate services, Emergency management, Flood risk, Decision support

New algorithms for motion error detection of numerical control machine tool by laser tracking measurement on the basis of GPS principle

Science.gov (United States)

Wang, Jindong; Chen, Peng; Deng, Yufen; Guo, Junjie

2018-01-01

As a three-dimensional measuring instrument, the laser tracker is widely used in industrial measurement. To avoid the influence of angle measurement error on the overall measurement accuracy, the multi-station and time-sharing measurement with a laser tracker is introduced on the basis of the global positioning system (GPS) principle in this paper. For the proposed method, how to accurately determine the coordinates of each measuring point by using a large amount of measured data is a critical issue. Taking detecting motion error of a numerical control machine tool, for example, the corresponding measurement algorithms are investigated thoroughly. By establishing the mathematical model of detecting motion error of a machine tool with this method, the analytical algorithm concerning on base station calibration and measuring point determination is deduced without selecting the initial iterative value in calculation. However, when the motion area of the machine tool is in a 2D plane, the coefficient matrix of base station calibration is singular, which generates a distortion result. In order to overcome the limitation of the original algorithm, an improved analytical algorithm is also derived. Meanwhile, the calibration accuracy of the base station with the improved algorithm is compared with that with the original analytical algorithm and some iterative algorithms, such as the Gauss-Newton algorithm and Levenberg-Marquardt algorithm. The experiment further verifies the feasibility and effectiveness of the improved algorithm. In addition, the different motion areas of the machine tool have certain influence on the calibration accuracy of the base station, and the corresponding influence of measurement error on the calibration result of the base station depending on the condition number of coefficient matrix are analyzed.

Application of quality by design principles to the development and technology transfer of a major process improvement for the manufacture of a recombinant protein.

Science.gov (United States)

Looby, Mairead; Ibarra, Neysi; Pierce, James J; Buckley, Kevin; O'Donovan, Eimear; Heenan, Mary; Moran, Enda; Farid, Suzanne S; Baganz, Frank

2011-01-01

This study describes the application of quality by design (QbD) principles to the development and implementation of a major manufacturing process improvement for a commercially distributed therapeutic protein produced in Chinese hamster ovary cell culture. The intent of this article is to focus on QbD concepts, and provide guidance and understanding on how the various components combine together to deliver a robust process in keeping with the principles of QbD. A fed-batch production culture and a virus inactivation step are described as representative examples of upstream and downstream unit operations that were characterized. A systematic approach incorporating QbD principles was applied to both unit operations, involving risk assessment of potential process failure points, small-scale model qualification, design and execution of experiments, definition of operating parameter ranges and process validation acceptance criteria followed by manufacturing-scale implementation and process validation. Statistical experimental designs were applied to the execution of process characterization studies evaluating the impact of operating parameters on product quality attributes and process performance parameters. Data from process characterization experiments were used to define the proven acceptable range and classification of operating parameters for each unit operation. Analysis of variance and Monte Carlo simulation methods were used to assess the appropriateness of process design spaces. Successful implementation and validation of the process in the manufacturing facility and the subsequent manufacture of hundreds of batches of this therapeutic protein verifies the approaches taken as a suitable model for the development, scale-up and operation of any biopharmaceutical manufacturing process. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

Globular and disordered-the non-identical twins in protein-protein interactions

DEFF Research Database (Denmark)

Teilum, Kaare; Olsen, Johan Gotthardt; Kragelund, Birthe Brandt

2015-01-01

as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those...... of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1)....

Design of a Cognitive Tool to Enhance Problemsolving Performance

Science.gov (United States)

Lee, Youngmin; Nelson, David

2005-01-01

The design of a cognitive tool to support problem-solving performance for external representation of knowledge is described. The limitations of conventional knowledge maps are analyzed in proposing the tool. The design principles and specifications are described. This tool is expected to enhance learners problem-solving performance by allowing…

Principles and tools for collaborative entity-based intelligence analysis.

Science.gov (United States)

Bier, Eric A; Card, Stuart K; Bodnar, John W

2010-01-01

Software tools that make it easier for analysts to collaborate as a natural part of their work will lead to better analysis that is informed by more perspectives. We are interested to know if software tools can be designed that support collaboration even as they allow analysts to find documents and organize information (including evidence, schemas, and hypotheses). We have modified the Entity Workspace system, described previously, to test such designs. We have evaluated the resulting design in both a laboratory study and a study where it is situated with an analysis team. In both cases, effects on collaboration appear to be positive. Key aspects of the design include an evidence notebook optimized for organizing entities (rather than text characters), information structures that can be collapsed and expanded, visualization of evidence that emphasizes events and documents (rather than emphasizing the entity graph), and a notification system that finds entities of mutual interest to multiple analysts. Long-term tests suggest that this approach can support both top-down and bottom-up styles of analysis.

Is Principled Pragmatism a Viable Framework for Addressing Complex Problems?

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Islam, S.

2017-12-01

Complex water problems are connected with many competing and often conflicting values, interests, and tools. These problems can't be addressed through simply applying dogmatic principles or a deal-making pragmatic approach. Because these problems are interconnected and interdependent, a final solution can't be pre-specified. Any intervention to a complex problem requires attention to both principles and pragmatism. Strict adherence to principles without pragmatism is often not actionable; pure pragmatism exercised without guiding principles is not sustainable. In a colloquial sense, pragmatism is often taken to suggest practical, opportunistic, and expedient approaches at the expense of principles. This perception appears to be rooted in the dichotomy between "being pragmatic" and "being ideological". The notion of principled pragmatism attempts to get away from this duality by focusing on how to make ideas clear and actionable. In other words, how to connect our thoughts to action given the context, constraints, and capacity. Principled pragmatism - rooted in equity and sustainability as guiding principles for water management - approach attempts to synthesize symbolic aspirations with realistic assessment to chart a trajectory of actionable subset of implementable solutions. Case studies from the Ganges Basin will show the utility of principled pragmatism for water management in a changing world.

Transformer design principles with applications to core-form power transformers

CERN Document Server

Del Vecchio, Robert M; Feeney, Mary-Ellen F

2001-01-01

Transformer Design Principles presents the theory of transformer operation and the methods and techniques of designing them. It emphasizes the physical principles and mathematical tools for simulating transformer behavior, including modern computer techniques. The scope of the book includes types of construction, circuit analysis, mechanical aspects of design, high voltage insulation requirements, and cooling design. The authors also address test procedures and reliability methods to assure successful design and discuss the economic analysis of designs. Summarizing material currently scattered

The rise of photoresponsive protein technologies applications in vivo: a spotlight on zebrafish developmental and cell biology [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Renee Wei-Yan Chow

2017-04-01

Full Text Available The zebrafish (Danio rerio is a powerful vertebrate model to study cellular and developmental processes in vivo. The optical clarity and their amenability to genetic manipulation make zebrafish a model of choice when it comes to applying optical techniques involving genetically encoded photoresponsive protein technologies. In recent years, a number of fluorescent protein and optogenetic technologies have emerged that allow new ways to visualize, quantify, and perturb developmental dynamics. Here, we explain the principles of these new tools and describe some of their representative applications in zebrafish.

Seeking high reliability in primary care: Leadership, tools, and organization.

Science.gov (United States)

Weaver, Robert R

2015-01-01

Leaders in health care increasingly recognize that improving health care quality and safety requires developing an organizational culture that fosters high reliability and continuous process improvement. For various reasons, a reliability-seeking culture is lacking in most health care settings. Developing a reliability-seeking culture requires leaders' sustained commitment to reliability principles using key mechanisms to embed those principles widely in the organization. The aim of this study was to examine how key mechanisms used by a primary care practice (PCP) might foster a reliability-seeking, system-oriented organizational culture. A case study approach was used to investigate the PCP's reliability culture. The study examined four cultural artifacts used to embed reliability-seeking principles across the organization: leadership statements, decision support tools, and two organizational processes. To decipher their effects on reliability, the study relied on observations of work patterns and the tools' use, interactions during morning huddles and process improvement meetings, interviews with clinical and office staff, and a "collective mindfulness" questionnaire. The five reliability principles framed the data analysis. Leadership statements articulated principles that oriented the PCP toward a reliability-seeking culture of care. Reliability principles became embedded in the everyday discourse and actions through the use of "problem knowledge coupler" decision support tools and daily "huddles." Practitioners and staff were encouraged to report unexpected events or close calls that arose and which often initiated a formal "process change" used to adjust routines and prevent adverse events from recurring. Activities that foster reliable patient care became part of the taken-for-granted routine at the PCP. The analysis illustrates the role leadership, tools, and organizational processes play in developing and embedding a reliable-seeking culture across an

Robust design principles for reducing variation in functional performance

DEFF Research Database (Denmark)

Christensen, Martin Ebro; Howard, Thomas J.

2016-01-01

This paper identifies, describes and classifies a comprehensive collection of variation reduction principles (VRP) that can be used to increase the robustness of a product and reduce its variation in functional performance. Performance variation has a negative effect on the reliability and percei......This paper identifies, describes and classifies a comprehensive collection of variation reduction principles (VRP) that can be used to increase the robustness of a product and reduce its variation in functional performance. Performance variation has a negative effect on the reliability...... and perceived quality of a product and efforts should be made to minimise it. The design principles are identified by a systematic decomposition of the Taguchi Transfer Function in combination with the use of existing literature and the authors’ experience. The paper presents 15 principles and describes...... their advantages and disadvantages along with example cases. Subsequently, the principles are classified based on their applicability in the various development and production stages. The VRP are to be added to existing robust design methodologies, helping the designer to think beyond robust design tool and method...

The four principles: can they be measured and do they predict ethical decision making?

Science.gov (United States)

Page, Katie

2012-05-20

The four principles of Beauchamp and Childress--autonomy, non-maleficence, beneficence and justice--have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

The four principles: Can they be measured and do they predict ethical decision making?

Directory of Open Access Journals (Sweden)

Page Katie

2012-05-01

Full Text Available Abstract Background The four principles of Beauchamp and Childress - autonomy, non-maleficence, beneficence and justice - have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. Methods The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. Results Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. Conclusions People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed.

The four principles: Can they be measured and do they predict ethical decision making?

Science.gov (United States)

2012-01-01

Background The four principles of Beauchamp and Childress - autonomy, non-maleficence, beneficence and justice - have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care. This study tests whether these principles can be quantitatively measured on an individual level, and then subsequently if they are used in the decision making process when individuals are faced with ethical dilemmas. Methods The Analytic Hierarchy Process was used as a tool for the measurement of the principles. Four scenarios, which involved conflicts between the medical ethical principles, were presented to participants who then made judgments about the ethicality of the action in the scenario, and their intentions to act in the same manner if they were in the situation. Results Individual preferences for these medical ethical principles can be measured using the Analytic Hierarchy Process. This technique provides a useful tool in which to highlight individual medical ethical values. On average, individuals have a significant preference for non-maleficence over the other principles, however, and perhaps counter-intuitively, this preference does not seem to relate to applied ethical judgements in specific ethical dilemmas. Conclusions People state they value these medical ethical principles but they do not actually seem to use them directly in the decision making process. The reasons for this are explained through the lack of a behavioural model to account for the relevant situational factors not captured by the principles. The limitations of the principles in predicting ethical decision making are discussed. PMID:22606995

Polymerase chain reaction as a tool for developing stress protein probes

Energy Technology Data Exchange (ETDEWEB)

Cochrane, B.J.; Mattley, Y.D. (Univ. of South Florida, Tampa, FL (United States). Dept. of Biology); Snell, T.W. (Georgia Inst. of Tech., Atlanta, GA (United States). Div. of Biology)

1994-08-01

Because of the high degree of evolutionary conservation of stress proteins, potential exists for the development of nucleic acid probes from particular species that could be used to monitor stress-related changes in mRNA abundance. The polymerase chain reaction (PCR) is a powerful tool that can be applied to the generation of these probes, provided that primer sequences can be identified that specifically amplify sequences of interest from a wide variety of organisms. The authors identified such sequences from multiple alignments of published chaperonin and stress-70 sequences, and tested their ability to amplify appropriately sized fragments from genomic DNA from a variety of vertebrates and invertebrates. Although no primer pair could be used successfully with all species, the authors were able to derive specific products from most species by testing different pairs. One primer pair for chaperonin proved particularly useful. Products were obtained from all tested species, and with a single exception (human), these primers appeared to amplify a single copy sequence. The authors determined the nucleotide sequence of the product obtained from the rotifer Brachionus plicatilis and determined by phylogenetic analysis of the inferred protein product that the product obtained is most likely derived from a rotifer DNA template. Finally, the authors show that this product can be used to detect changes in abundance of homologous mRNA in heat-stressed rotifers.

TAPAS: tools to assist the targeted protein quantification of human alternative splice variants.

Science.gov (United States)

Yang, Jae-Seong; Sabidó, Eduard; Serrano, Luis; Kiel, Christina

2014-10-15

In proteomes of higher eukaryotes, many alternative splice variants can only be detected by their shared peptides. This makes it highly challenging to use peptide-centric mass spectrometry to distinguish and to quantify protein isoforms resulting from alternative splicing events. We have developed two complementary algorithms based on linear mathematical models to efficiently compute a minimal set of shared and unique peptides needed to quantify a set of isoforms and splice variants. Further, we developed a statistical method to estimate the splice variant abundances based on stable isotope labeled peptide quantities. The algorithms and databases are integrated in a web-based tool, and we have experimentally tested the limits of our quantification method using spiked proteins and cell extracts. The TAPAS server is available at URL http://davinci.crg.es/tapas/. luis.serrano@crg.eu or christina.kiel@crg.eu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A new design of automatic vertical drilling tool

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Yanfeng Ma

2015-09-01

Full Text Available In order to effectively improve penetration rates and enhance wellbore quality for vertical wells, a new Automatic Vertical Drilling Tool (AVDT based on Eccentric Braced Structure (EBS is designed. Applying operating principle of rotary steering drilling, AVDT adds offset gravity block automatic induction inclination mechanism. When hole straightening happens, tools take essentric moment to be produced by gravity of offset gravity lock to control the bearing of guide force, so that well straightening is achieved. The normal tool's size of the AVDT is designed as 215.9 mm，other major components' sizes are worked out by the result of theoretical analysis, including the offset angle of EBS. This paper aims to introduce the structure, operating principle, theoretical analysis and describe the key components' parameters setting of the AVDT.

“Biotecnological War” - A Conceptual And Perceptual Assessment Tool For Teaching Biotechnology And Protein Chemistry For Undergraduate Students In Biological Sciences.

Directory of Open Access Journals (Sweden)

C. R. C. Cruz et al.

2017-07-01

Full Text Available "Biotecnological War" board game, a conceptual and perceptual assessment tool for biotechnology and protein chemistry teaching for undergraduate students in biological sciences and related areas. It is a proposal initially conceived as an alternative complementary tool for biochemistry teaching of proteins and peptides, challenging students, aiming to review concepts transmitted in classroom, stimulating diverse student’s abilities, such as their creativity, competitiveness and resource management. OBJECTIVES. Correlate biochemistry importance of proteins and peptides with the development of new products. MATERIAL AND METHODS. Firstly, theoretical-practical classes were given with seminars to be presented by the groups, including topics that will be addressed in game. Groups of 5 students, with previously viewed themes drawn a goal to be achieved. There are two drawn goals variations: Academic or Commercial. Board is divided into provinces, which must be bought with an initial resource to complete the goal. Before the beginning each group will have 15 minutes to plan their actions. The objective is to develop the entire objective drawn with appropriate methodology, having at least 1 territory in each province. RESULTS. This game proved to be an excellent tool for complementary evaluation of students, which stimulated teamwork and a strong competitive spirit within classroom, which allowed to analyze students' perception regarding the protein subject and team work. On the other hand, for teacher and students participating in compulsory traineeship program this game demonstrated new ways to approach complex subjects in biochemistry using creativity with the development of new activities such as this board game. CONCLUSION: Overall, students had a good impression of “Biotecnological war” game since it helped to secure and administer the protein and peptides biochemical subject in a competitive and team work way.

Protein Data Bank Japan (PDBj): updated user interfaces, resource description framework, analysis tools for large structures.

Science.gov (United States)

Kinjo, Akira R; Bekker, Gert-Jan; Suzuki, Hirofumi; Tsuchiya, Yuko; Kawabata, Takeshi; Ikegawa, Yasuyo; Nakamura, Haruki

2017-01-04

The Protein Data Bank Japan (PDBj, http://pdbj.org), a member of the worldwide Protein Data Bank (wwPDB), accepts and processes the deposited data of experimentally determined macromolecular structures. While maintaining the archive in collaboration with other wwPDB partners, PDBj also provides a wide range of services and tools for analyzing structures and functions of proteins. We herein outline the updated web user interfaces together with RESTful web services and the backend relational database that support the former. To enhance the interoperability of the PDB data, we have previously developed PDB/RDF, PDB data in the Resource Description Framework (RDF) format, which is now a wwPDB standard called wwPDB/RDF. We have enhanced the connectivity of the wwPDB/RDF data by incorporating various external data resources. Services for searching, comparing and analyzing the ever-increasing large structures determined by hybrid methods are also described. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Meta-Analyses of Seven of NIDA’s Principles of Drug Addiction Treatment

Science.gov (United States)

Pearson, Frank S.; Prendergast, Michael L.; Podus, Deborah; Vazan, Peter; Greenwell, Lisa; Hamilton, Zachary

2011-01-01

Seven of the 13 Principles of Drug Addiction Treatment disseminated by the National Institute on Drug Abuse (NIDA) were meta-analyzed as part of the Evidence-based Principles of Treatment (EPT) project. By averaging outcomes over the diverse programs included in EPT, we found that five of the NIDA principles examined are supported: matching treatment to the client’s needs; attending to the multiple needs of clients; behavioral counseling interventions; treatment plan reassessment; and counseling to reduce risk of HIV. Two of the NIDA principles are not supported: remaining in treatment for an adequate period of time and frequency of testing for drug use. These weak effects could be the result of the principles being stated too generally to apply to the diverse interventions and programs that exist or of unmeasured moderator variables being confounded with the moderators that measured the principles. Meta-analysis should be a standard tool for developing principles of effective treatment for substance use disorders. PMID:22119178

Development of Genome Engineering Tools from Plant-Specific PPR Proteins Using Animal Cultured Cells.

Science.gov (United States)

Kobayashi, Takehito; Yagi, Yusuke; Nakamura, Takahiro

2016-01-01

The pentatricopeptide repeat (PPR) motif is a sequence-specific RNA/DNA-binding module. Elucidation of the RNA/DNA recognition mechanism has enabled engineering of PPR motifs as new RNA/DNA manipulation tools in living cells, including for genome editing. However, the biochemical characteristics of PPR proteins remain unknown, mostly due to the instability and/or unfolding propensities of PPR proteins in heterologous expression systems such as bacteria and yeast. To overcome this issue, we constructed reporter systems using animal cultured cells. The cell-based system has highly attractive features for PPR engineering: robust eukaryotic gene expression; availability of various vectors, reagents, and antibodies; highly efficient DNA delivery ratio (>80 %); and rapid, high-throughput data production. In this chapter, we introduce an example of such reporter systems: a PPR-based sequence-specific translational activation system. The cell-based reporter system can be applied to characterize plant genes of interested and to PPR engineering.

The biology of non-native proteins

NARCIS (Netherlands)

Herczenik, E.

2007-01-01

Protein misfolding diseases are linked by common principles of protein aggregation, plaque development and tissue damage. There is no adequate therapy for these highly debilitating diseases. This thesis aims to increase the understanding of protein misfolding diseases, which will hopefully lead to

The Sabatier Principle Illustrated by Catalytic H2O2 Decomposition on Metal Surfaces

DEFF Research Database (Denmark)

Laursen, Anders Bo; Man, Isabela Costinela; Trinhammer, Ole

2011-01-01

Heterogeneous catalysis is important in today’s industry. Hence, it is imperative to introduce students to this field and its tools. A new way of introducing one of these tools, the Sabatier principle, via a laboratory exercise is presented. A volcano plot is constructed for the well-known hetero......Heterogeneous catalysis is important in today’s industry. Hence, it is imperative to introduce students to this field and its tools. A new way of introducing one of these tools, the Sabatier principle, via a laboratory exercise is presented. A volcano plot is constructed for the well......-known heterogeneous H2O2 catalytic decomposition reaction on various metal foils. The activity per catalyst surface area versus the computationally calculated binding energy of OH groups on the catalysts is plotted. The OH group is identified as the only surface intermediate in an intuitive reaction mechanism...

The Elements and Principles of Design: A Baseline Study

Science.gov (United States)

Adams, Erin

2013-01-01

Critical to the discipline, both professionally and academically, are the fundamentals of interior design. These fundamentals include the elements and principles of interior design: the commonly accepted tools and vocabulary used to create and communicate successful interior environments. Research indicates a lack of consistency in both the…

Engineering bacterial translation initiation - Do we have all the tools we need?

Science.gov (United States)

Vigar, Justin R J; Wieden, Hans-Joachim

2017-11-01

Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts. Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals. Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools. Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier

Using microbes as a key tool to unravel the mechanism of autophagy and the functions of the ATG proteins

Directory of Open Access Journals (Sweden)

Mario Mauthe

2016-12-01

Full Text Available The study of microbe infections has always been a very effective approach to unveil and dissect cellular pathways. Autophagy is not an exception. Although some of the breakthrough discoveries in the field were obtained using yeast, pathogens have been and still are a great tool to discover and characterize new molecular and functional aspects of autophagy. Research on pathogens has helped to acquire knowledge about selective types of autophagy and the assembly of the autophagy machinery, i.e the autophagy-related (ATG proteins, but also about alternative cellular roles of this pathway, such as secretion. Finally, microbes have also served to discover and characterize unconventional functions of the ATG proteins, which are uncoupled from their role in autophagy. In our recent study, we have taken advantage of viruses as a screening tool to determine the extent of the unconventional functions of the ATG proteome and characterize one of them.

Principles for Helpful Sequence and Deduction of Knowledge Organization Systems - An Exploratory Study

Directory of Open Access Journals (Sweden)

Asundi, A.Y.

2013-06-01

Full Text Available Dr. Ranganathan's "Principles for Helpful Sequence" among the set of normative principles play an exclusive role in the arrangement of subject isolates. Each subject in the universe of subjects is regulated by a guiding principle of its own which analogously determines the sequence of Arrays in ordering the subject surrogates or isolates. For example, the "Principle of Later-in-Evolution" is applied for sequencing isolates of Animal and Plant Species; this concept can be applied to one of the tools of KOS viz. Taxonomies. The application of Principles for Helpful Sequence is summarily presented and in the process the paper highlights the inherent elements of knowledge organization in each one of these principles in a manner that might map the future course of research in this area with the potentiality to bring about a relation between principles for helpful sequence and KOS.

The radiation protection principles model as a tool in the e-waste procedures

Energy Technology Data Exchange (ETDEWEB)

Tsitomeneas, S. Th., E-mail: stsit@teipir.gr [Piraeus University of Applied Sciences, Aigaleo (Greece); Vourlias, K., E-mail: kvourlias@yahoo.gr [Aristotle University of Thessaloniki (Greece); Geronikolou, St. A., E-mail: sgeronik@bioacademy.gr [Biomedical Research Foundation Academy of Athens, Athens (Greece)

2016-03-25

The electrical and electronic waste (e-waste) management is a global environmental problem dominated by the precautionary principle application, resulted to preliminary and ambiguous potential adverse effects, of extensive scientific uncertainty. In order to overcome the detected stochastic effects confusions in this field, we propose the inclusion of the principles of justification-optimization-limitation and of prudent avoidance. This model is already, established in radiation protection, so that toxicity as a result of the e-waste management would decrease, whilst the precious metals would be saved. We, further, resolve the classification of rejected items as reusable or as waste, so that the procedure of dismantling and recycling becomes easier, and the collecting-transporting-placement at an e-waste landfill would be safer. In conclusion, our proposing pattern in the e-waste management enforces the sustainable reducing-reusing-recycling, saves time/money and advances safety by including more sources of e-waste (military, medical etc) that were excluded previously.

The radiation protection principles model as a tool in the e-waste procedures

International Nuclear Information System (INIS)

Tsitomeneas, S. Th.; Vourlias, K.; Geronikolou, St. A.

2016-01-01

The electrical and electronic waste (e-waste) management is a global environmental problem dominated by the precautionary principle application, resulted to preliminary and ambiguous potential adverse effects, of extensive scientific uncertainty. In order to overcome the detected stochastic effects confusions in this field, we propose the inclusion of the principles of justification-optimization-limitation and of prudent avoidance. This model is already, established in radiation protection, so that toxicity as a result of the e-waste management would decrease, whilst the precious metals would be saved. We, further, resolve the classification of rejected items as reusable or as waste, so that the procedure of dismantling and recycling becomes easier, and the collecting-transporting-placement at an e-waste landfill would be safer. In conclusion, our proposing pattern in the e-waste management enforces the sustainable reducing-reusing-recycling, saves time/money and advances safety by including more sources of e-waste (military, medical etc) that were excluded previously.

Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription

Directory of Open Access Journals (Sweden)

Santoro Thomas J

2005-02-01

Full Text Available Abstract Background In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2 is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS. The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine. Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. Methods Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. Results The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti

Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.

Science.gov (United States)

Tomita, Michiyo; Holman, Brita J; Santoro, Christopher P; Santoro, Thomas J

2005-02-25

BACKGROUND: In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine.Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. METHODS: Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. RESULTS: The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti-oxidant, epigallocatechin

[Tool of nutrition education for allergic to egg and cow's milk protein in pediatric age].

Science.gov (United States)

San Mauro Martín, Ismael

2014-05-01

Food allergy affects a large part of the population and their numbers are increasing. Although the knowing of this pathology is growing, allergic patients have really difficulties to lead a normal life, especially with food. Until now,this group hadn t practical tools that would help them in the development of a balanced daily diet, as there are for the general population in the form of pyramids and dietary guidelines . This work has covered this need for two of the most prevalent allergies in early life. gather information on the allergy of cow's milk protein and egg, to design a food pyramid for these patients, based on the consensus, recommendations and scientific guidance. After confirming the absence of a similar work, food pyramids allergy to egg and cow's milk protein, adapted to each, and a joint pyramid is designed to both allergies. Besides basic recommendations for healthy eating were included in general and in particular individuals, with special interest for the collective (food hygiene, food additives, cosmetics, medicines, etc). Due to the importance of nutrition in childhood and acquires the underlying difficulties this group, to properly plan the diet is very important as it can prevent accidents and long-term nutritional deficiencies. Therefore provide graphical tools and practices to this goal, is importance for population and medical and scientific community, and is the result of this work. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Hydrogen Financial Analysis Scenario Tool (H2FAST). Web Tool User's Manual

Energy Technology Data Exchange (ETDEWEB)

Bush, B. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Penev, M. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Melaina, M. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Zuboy, J. [Independent Consultant, Golden, CO (United States)

2015-05-11

The Hydrogen Financial Analysis Scenario Tool (H2FAST) provides a quick and convenient indepth financial analysis for hydrogen fueling stations. This manual describes how to use the H2FAST web tool, which is one of three H2FAST formats developed by the National Renewable Energy Laboratory (NREL). Although all of the formats are based on the same financial computations and conform to generally accepted accounting principles (FASAB 2014, Investopedia 2014), each format provides a different level of complexity and user interactivity.

When does a protein become an allergen? Searching for a dynamic definition based on most advanced technology tools.

Science.gov (United States)

Mari, A

2008-07-01

Since the early beginning of allergology as a science considerable efforts have been made by clinicians and researchers to identify and characterize allergic triggers as raw allergenic materials, allergenic sources and tissues, and more recently basic allergenic structures defined as molecules. The last 15-20 years have witnessed many centres focusing on the identification and characterization of allergenic molecules leading to an expanding wealth of knowledge. The need to organize this information leads to the most important question 'when does a protein become an allergen?' In this article, I try to address this question by reviewing a few basic concepts of the immunology of IgE-mediated diseases, reporting on the current diagnostic and epidemiological tools used for allergic disease studies and discussing the usefulness of novel biotechnology tools (i.e. proteomics and molecular biology approaches), information technology tools (i.e. Internet-based resources) and microtechnology tools (i.e. proteomic microarray for IgE testing on molecular allergens). A step-wise staging of the identification and characterization process, including bench, clinical and epidemiological aspects, is proposed, in order to classify allergenic molecules dynamically. This proposal reflects the application and use of all the new tools available from current technologies.

Pathogenesis-related proteins and peptides as promising tools for engineering plants with multiple stress tolerance.

Science.gov (United States)

Ali, Sajad; Ganai, Bashir Ahmad; Kamili, Azra N; Bhat, Ajaz Ali; Mir, Zahoor Ahmad; Bhat, Javaid Akhter; Tyagi, Anshika; Islam, Sheikh Tajamul; Mushtaq, Muntazir; Yadav, Prashant; Rawat, Sandhya; Grover, Anita

Pathogenesis-related (PR) proteins and antimicrobial peptides (AMPs) are a group of diverse molecules that are induced by phytopathogens as well as defense related signaling molecules. They are the key components of plant innate immune system especially systemic acquired resistance (SAR), and are widely used as diagnostic molecular markers of defense signaling pathways. Although, PR proteins and peptides have been isolated much before but their biological function remains largely enigmatic despite the availability of new scientific tools. The earlier studies have demonstrated that PR genes provide enhanced resistance against both biotic and abiotic stresses, which make them one of the most promising candidates for developing multiple stress tolerant crop varieties. In this regard, plant genetic engineering technology is widely accepted as one of the most fascinating approach to develop the disease resistant transgenic crops using different antimicrobial genes like PR genes. Overexpression of PR genes (chitinase, glucanase, thaumatin, defensin and thionin) individually or in combination have greatly uplifted the level of defense response in plants against a wide range of pathogens. However, the detailed knowledge of signaling pathways that regulates the expression of these versatile proteins is critical for improving crop plants to multiple stresses, which is the future theme of plant stress biology. Hence, this review provides an overall overview on the PR proteins like their classification, role in multiple stresses (biotic and abiotic) as well as in various plant defense signaling cascades. We also highlight the success and snags of transgenic plants expressing PR proteins and peptides. Copyright © 2018 Elsevier GmbH. All rights reserved.

Physical acoustics principles and methods

CERN Document Server

Mason, Warren P

1964-01-01

Physical Acoustics: Principles and Methods, Volume l-Part A focuses on high frequency sound waves in gases, liquids, and solids that have been proven as powerful tools in analyzing the molecular, defect, domain wall, and other types of motions. The selection first tackles wave propagation in fluids and normal solids and guided wave propagation in elongated cylinders and plates. Discussions focus on fundamentals of continuum mechanics; small-amplitude waves in a linear viscoelastic medium; representation of oscillations and waves; and special effects associated with guided elastic waves in plat

The Search Engine for Multi-Proteoform Complexes: An Online Tool for the Identification and Stoichiometry Determination of Protein Complexes.

Science.gov (United States)

Skinner, Owen S; Schachner, Luis F; Kelleher, Neil L

2016-12-08

Recent advances in top-down mass spectrometry using native electrospray now enable the analysis of intact protein complexes with relatively small sample amounts in an untargeted mode. Here, we describe how to characterize both homo- and heteropolymeric complexes with high molecular specificity using input data produced by tandem mass spectrometry of whole protein assemblies. The tool described is a "search engine for multi-proteoform complexes," (SEMPC) and is available for free online. The output is a list of candidate multi-proteoform complexes and scoring metrics, which are used to define a distinct set of one or more unique protein subunits, their overall stoichiometry in the intact complex, and their pre- and post-translational modifications. Thus, we present an approach for the identification and characterization of intact protein complexes from native mass spectrometry data. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Quality Management Principles in the Management of Shipboard Discharges

Directory of Open Access Journals (Sweden)

Vjekoslav Koljatić

2006-05-01

Full Text Available Environmental control of vessels is a management functionthat requires applied technology, training and diligentmanagement. Quality Management is a tool for developing environmentalprograms to control corporate environmental exposures.The management of environmental regulations, requirementsand concerns requires a systematic approach. QualityManagement (QM embodies principles of policy delineation,operations accountability, documentation and review.These principles are all transferable to most aspects of shipmanagement. Properly implemented, they assign respective responsibilitiesfor both shore side and shipboard staff Both ISMand IS0-9000 Certification requirements embody the principlesof QM as requirements for certification. If, however, onelooks beyond the certification process, these principles makegood business sense. The benefits of QM are both economic aswell as assisting in corporate risk management. This paper willfocus on the risk management benefits as they apply of environmentalhealth programs in the marine environment includingports.

A simple tool for tubing modification to improve spiral high-speed counter-current chromatography for protein purification.

Science.gov (United States)

Ito, Yoichiro; Ma, Xiaofeng; Clary, Robert

2016-01-01

A simple tool is introduced which can modify the shape of tubing to enhance the partition efficiency in high-speed countercurrent chromatography. It consists of a pair of interlocking identical gears, each coaxially holding a pressing wheel to intermittently compress plastic tubing in 0 - 10 mm length at every 1 cm interval. The performance of the processed tubing is examined in protein separation with 1.6 mm ID PTFE tubing intermittently pressed in 3 mm and 10 mm width both at 10 mm intervals at various flow rates and revolution speeds. A series of experiments was performed with a polymer phase system composed of polyethylene glycol and dibasic potassium phosphate each at 12.5% (w/w) in deionized water using three protein samples. Overall results clearly demonstrate that the compressed tubing can yield substantially higher peak resolution than the non-processed tubing. The simple tubing modifier is very useful for separation of proteins with high-speed countercurrent chromatography.

Ethical Principles in European regulation of biotechnology - possibilities and pitfalls

DEFF Research Database (Denmark)

Faber, Berit Andersen; Nielsen, Linda

2002-01-01

The purpose of this report is to discribe, analyse and assess the varying methods of operationalising ethical principles within European regulation of biotechnology, with the inclusion of proposals for different tools and models for use in future regulation. The aim of the report is first...

Integrated structural biology to unravel molecular mechanisms of protein-RNA recognition.

Science.gov (United States)

Schlundt, Andreas; Tants, Jan-Niklas; Sattler, Michael

2017-04-15

Recent advances in RNA sequencing technologies have greatly expanded our knowledge of the RNA landscape in cells, often with spatiotemporal resolution. These techniques identified many new (often non-coding) RNA molecules. Large-scale studies have also discovered novel RNA binding proteins (RBPs), which exhibit single or multiple RNA binding domains (RBDs) for recognition of specific sequence or structured motifs in RNA. Starting from these large-scale approaches it is crucial to unravel the molecular principles of protein-RNA recognition in ribonucleoprotein complexes (RNPs) to understand the underlying mechanisms of gene regulation. Structural biology and biophysical studies at highest possible resolution are key to elucidate molecular mechanisms of RNA recognition by RBPs and how conformational dynamics, weak interactions and cooperative binding contribute to the formation of specific, context-dependent RNPs. While large compact RNPs can be well studied by X-ray crystallography and cryo-EM, analysis of dynamics and weak interaction necessitates the use of solution methods to capture these properties. Here, we illustrate methods to study the structure and conformational dynamics of protein-RNA complexes in solution starting from the identification of interaction partners in a given RNP. Biophysical and biochemical techniques support the characterization of a protein-RNA complex and identify regions relevant in structural analysis. Nuclear magnetic resonance (NMR) is a powerful tool to gain information on folding, stability and dynamics of RNAs and characterize RNPs in solution. It provides crucial information that is complementary to the static pictures derived from other techniques. NMR can be readily combined with other solution techniques, such as small angle X-ray and/or neutron scattering (SAXS/SANS), electron paramagnetic resonance (EPR), and Förster resonance energy transfer (FRET), which provide information about overall shapes, internal domain

Five-axis Control Processing Using NC Machine Tools : A Tool Posture Decision Using the Tangent Slope at a Cut Point on a Work

OpenAIRE

小島, 龍広; 西田, 知照; 扇谷, 保彦

2003-01-01

This report deals with the way to decide tool posture and the way to analytically calculate tool path for the work shape requiring 5-axis control machining. In the tool path calculation, basic equations are derived using the principle that the tangent slope at a cut point on a work and the one at a cutting point on a tool edge are identical. A tool posture decision procedure using the tangent slope at each cut point on a work is proposed for any shape of tool edge. The valid- ity of the way t...

Modeling Electric Discharges with Entropy Production Rate Principles

Directory of Open Access Journals (Sweden)

Thomas Christen

2009-12-01

Full Text Available Under which circumstances are variational principles based on entropy production rate useful tools for modeling steady states of electric (gas discharge systems far from equilibrium? It is first shown how various different approaches, as Steenbeck’s minimum voltage and Prigogine’s minimum entropy production rate principles are related to the maximum entropy production rate principle (MEPP. Secondly, three typical examples are discussed, which provide a certain insight in the structure of the models that are candidates for MEPP application. It is then thirdly argued that MEPP, although not being an exact physical law, may provide reasonable model parameter estimates, provided the constraints contain the relevant (nonlinear physical effects and the parameters to be determined are related to disregarded weak constraints that affect mainly global entropy production. Finally, it is additionally conjectured that a further reason for the success of MEPP in certain far from equilibrium systems might be based on a hidden linearity of the underlying kinetic equation(s.

Solar radiation as a forest management tool: a primer of principles and application

Science.gov (United States)

Howard G. Halverson; James L. Smith

1979-01-01

Forests are products of solar radiation use. The sun also drives the hydrologic cycle on forested watersheds. Some basic concepts of climatology and solar radiation are summarized in including earth-sun relations, polar tilt, solar energy, terrestrial energy, energy balance, and local energy. An example shows how these principles can be applied in resource management....

Reducing waste and errors: piloting lean principles at Intermountain Healthcare.

Science.gov (United States)

Jimmerson, Cindy; Weber, Dorothy; Sobek, Durward K

2005-05-01

The Toyota Production System (TPS), based on industrial engineering principles and operational innovations, is used to achieve waste reduction and efficiency while increasing product quality. Several key tools and principles, adapted to health care, have proved effective in improving hospital operations. Value Stream Maps (VSMs), which represent the key people, material, and information flows required to deliver a product or service, distinguish between value-adding and non-value-adding steps. The one-page Problem-Solving A3 Report guides staff through a rigorous and systematic problem-solving process. PILOT PROJECT at INTERMOUNTAIN HEALTHCARE: In a pilot project, participants made many improvements, ranging from simple changes implemented immediately (for example, heart monitor paper not available when a patient presented with a dysrythmia) to larger projects involving patient or information flow issues across multiple departments. Most of the improvements required little or no investment and reduced significant amounts of wasted time for front-line workers. In one unit, turnaround time for pathologist reports from an anatomical pathology lab was reduced from five to two days. TPS principles and tools are applicable to an endless variety of processes and work settings in health care and can be used to address critical challenges such as medical errors, escalating costs, and staffing shortages.

An exploration of inter-organisational partnership assessment tools in the context of Australian Aboriginal-mainstream partnerships: a scoping review of the literature.

Science.gov (United States)

Tsou, Christina; Haynes, Emma; Warner, Wayne D; Gray, Gordon; Thompson, Sandra C

2015-04-23

The need for better partnerships between Aboriginal organisations and mainstream agencies demands attention on process and relational elements of these partnerships, and improving partnership functioning through transformative or iterative evaluation procedures. This paper presents the findings of a literature review which examines the usefulness of existing partnership tools to the Australian Aboriginal-mainstream partnership (AMP) context. Three sets of best practice principles for successful AMP were selected based on authors' knowledge and experience. Items in each set of principles were separated into process and relational elements and used to guide the analysis of partnership assessment tools. The review and analysis of partnership assessment tools were conducted in three distinct but related parts. Part 1- identify and select reviews of partnership tools; part 2 - identify and select partnership self-assessment tool; part 3 - analysis of selected tools using AMP principles. The focus on relational and process elements in the partnership tools reviewed is consistent with the focus of Australian AMP principles by reconciliation advocates; however, historical context, lived experience, cultural context and approaches of Australian Aboriginal people represent key deficiencies in the tools reviewed. The overall assessment indicated that the New York Partnership Self-Assessment Tool and the VicHealth Partnership Analysis Tools reflect the greatest number of AMP principles followed by the Nuffield Partnership Assessment Tool. The New York PSAT has the strongest alignment with the relational elements while VicHealth and Nuffield tools showed greatest alignment with the process elements in the chosen AMP principles. Partnership tools offer opportunities for providing evidence based support to partnership development. The multiplicity of tools in existence and the reported uniqueness of each partnership, mean the development of a generic partnership analysis for AMP

Endocrine Disruptor Screening Program (EDSP) Universe of Chemicals and General Validation Principles

Science.gov (United States)

This document was developed by the EPA to provide guidance to staff and managers regarding the EDSP universe of chemicals and general validation principles for consideration of computational toxicology tools for chemical prioritization.

Enhancing the productivity of soluble green fluorescent protein ...

African Journals Online (AJOL)

Protein sequences might have been evolved against different environmental pressures, which results in non-optimum properties in their stability, activity and folding efficiency. Directed evolution and consensus-based engineering of proteins are the protein engineering principles for the re-evolution of such natural proteins ...

PCE: web tools to compute protein continuum electrostatics

Science.gov (United States)

Miteva, Maria A.; Tufféry, Pierre; Villoutreix, Bruno O.

2005-01-01

PCE (protein continuum electrostatics) is an online service for protein electrostatic computations presently based on the MEAD (macroscopic electrostatics with atomic detail) package initially developed by D. Bashford [(2004) Front Biosci., 9, 1082–1099]. This computer method uses a macroscopic electrostatic model for the calculation of protein electrostatic properties, such as pKa values of titratable groups and electrostatic potentials. The MEAD package generates electrostatic energies via finite difference solution to the Poisson–Boltzmann equation. Users submit a PDB file and PCE returns potentials and pKa values as well as color (static or animated) figures displaying electrostatic potentials mapped on the molecular surface. This service is intended to facilitate electrostatics analyses of proteins and thereby broaden the accessibility to continuum electrostatics to the biological community. PCE can be accessed at . PMID:15980492

Combining biophysical methods for the analysis of protein complex stoichiometry and affinity in SEDPHAT

International Nuclear Information System (INIS)

Zhao, Huaying; Schuck, Peter

2015-01-01

Global multi-method analysis for protein interactions (GMMA) can increase the precision and complexity of binding studies for the determination of the stoichiometry, affinity and cooperativity of multi-site interactions. The principles and recent developments of biophysical solution methods implemented for GMMA in the software SEDPHAT are reviewed, their complementarity in GMMA is described and a new GMMA simulation tool set in SEDPHAT is presented. Reversible macromolecular interactions are ubiquitous in signal transduction pathways, often forming dynamic multi-protein complexes with three or more components. Multivalent binding and cooperativity in these complexes are often key motifs of their biological mechanisms. Traditional solution biophysical techniques for characterizing the binding and cooperativity are very limited in the number of states that can be resolved. A global multi-method analysis (GMMA) approach has recently been introduced that can leverage the strengths and the different observables of different techniques to improve the accuracy of the resulting binding parameters and to facilitate the study of multi-component systems and multi-site interactions. Here, GMMA is described in the software SEDPHAT for the analysis of data from isothermal titration calorimetry, surface plasmon resonance or other biosensing, analytical ultracentrifugation, fluorescence anisotropy and various other spectroscopic and thermodynamic techniques. The basic principles of these techniques are reviewed and recent advances in view of their particular strengths in the context of GMMA are described. Furthermore, a new feature in SEDPHAT is introduced for the simulation of multi-method data. In combination with specific statistical tools for GMMA in SEDPHAT, simulations can be a valuable step in the experimental design

The Swiss-Prot protein knowledgebase and ExPASy: providing the plant community with high quality proteomic data and tools.

Science.gov (United States)

Schneider, Michel; Tognolli, Michael; Bairoch, Amos

2004-12-01

The Swiss-Prot protein knowledgebase provides manually annotated entries for all species, but concentrates on the annotation of entries from model organisms to ensure the presence of high quality annotation of representative members of all protein families. A specific Plant Protein Annotation Program (PPAP) was started to cope with the increasing amount of data produced by the complete sequencing of plant genomes. Its main goal is the annotation of proteins from the model plant organism Arabidopsis thaliana. In addition to bibliographic references, experimental results, computed features and sometimes even contradictory conclusions, direct links to specialized databases connect amino acid sequences with the current knowledge in plant sciences. As protein families and groups of plant-specific proteins are regularly reviewed to keep up with current scientific findings, we hope that the wealth of information of Arabidopsis origin accumulated in our knowledgebase, and the numerous software tools provided on the Expert Protein Analysis System (ExPASy) web site might help to identify and reveal the function of proteins originating from other plants. Recently, a single, centralized, authoritative resource for protein sequences and functional information, UniProt, was created by joining the information contained in Swiss-Prot, Translation of the EMBL nucleotide sequence (TrEMBL), and the Protein Information Resource-Protein Sequence Database (PIR-PSD). A rising problem is that an increasing number of nucleotide sequences are not being submitted to the public databases, and thus the proteins inferred from such sequences will have difficulties finding their way to the Swiss-Prot or TrEMBL databases.

SU-E-T-191: PITSTOP: Process Improvement Techniques, Software Tools, and Operating Principles for a Quality Initiative Discovery Framework.

Science.gov (United States)

Siochi, R

2012-06-01

To develop a quality initiative discovery framework using process improvement techniques, software tools and operating principles. Process deviations are entered into a radiotherapy incident reporting database. Supervisors use an in-house Event Analysis System (EASy) to discuss incidents with staff. Major incidents are analyzed with an in-house Fault Tree Analysis (FTA). A meta-Analysis is performed using association, text mining, key word clustering, and differential frequency analysis. A key operating principle encourages the creation of forcing functions via rapid application development. 504 events have been logged this past year. The results for the key word analysis indicate that the root cause for the top ranked key words was miscommunication. This was also the root cause found from association analysis, where 24% of the time that an event involved a physician it also involved a nurse. Differential frequency analysis revealed that sharp peaks at week 27 were followed by 3 major incidents, two of which were dose related. The peak was largely due to the front desk which caused distractions in other areas. The analysis led to many PI projects but there is still a major systematic issue with the use of forms. The solution we identified is to implement Smart Forms to perform error checking and interlocking. Our first initiative replaced our daily QA checklist with a form that uses custom validation routines, preventing therapists from proceeding with treatments until out of tolerance conditions are corrected. PITSTOP has increased the number of quality initiatives in our department, and we have discovered or confirmed common underlying causes of a variety of seemingly unrelated errors. It has motivated the replacement of all forms with smart forms. © 2012 American Association of Physicists in Medicine.

Analysis of logging data from nuclear borehole tools

International Nuclear Information System (INIS)

Hovgaard, J.; Oelgaard, P.L.

1989-12-01

The processing procedure for logging data from a borehole of the Stenlille project of Dansk Naturgas A/S has been analysed. The tools considered in the analysis were an integral, natural-gamma tool, a neutron porosity tool, a gamma density tool and a caliper tool. It is believed that in most cases the processing procedure used by the logging company in the interpretation of the raw data is fully understood. An exception is the epithermal part of the neutron porosity tool where all data needed for an interpretation were not available. The analysis has shown that some parts of the interpretation procedure may not be consistent with the physical principle of the tools. (author)

The philosophical background: from principles to rules and analysis.

Science.gov (United States)

Sommerville, Ann

2002-01-01

Encounters between doctors and patients are subtle but complex forms of social interaction. Attempts to regulate aspects of the doctor-patient relationship have a long history. Initially, the production of guidance on principles and conduct was the domain of practitioners. In the 21st century, modern medical ethics still reflects some of this traditional thinking even though the responsibility for formulating ethical guidance increasingly falls to policy-makers, lawyers and theoreticians rather than doctors. Ethical concepts are also increasingly interwoven with contemporaneous concepts of patient autonomy, human rights and law. In a brief and necessarily sketchy overview of some of the key influences on European ethical development, this article traces the development of medical ethics through three broad stages: from principles to rules to providing tools for detailed moral analysis. It also discusses whether the original Hippocratic principles still find echo with modern doctors. Copyright 2002 S. Karger AG, Basel

Bernoulli's Principle

Science.gov (United States)

Hewitt, Paul G.

2004-01-01

Some teachers have difficulty understanding Bernoulli's principle particularly when the principle is applied to the aerodynamic lift. Some teachers favor using Newton's laws instead of Bernoulli's principle to explain the physics behind lift. Some also consider Bernoulli's principle too difficult to explain to students and avoid teaching it…

CellMap visualizes protein-protein interactions and subcellular localization

Science.gov (United States)

Dallago, Christian; Goldberg, Tatyana; Andrade-Navarro, Miguel Angel; Alanis-Lobato, Gregorio; Rost, Burkhard

2018-01-01

Many tools visualize protein-protein interaction (PPI) networks. The tool introduced here, CellMap, adds one crucial novelty by visualizing PPI networks in the context of subcellular localization, i.e. the location in the cell or cellular component in which a PPI happens. Users can upload images of cells and define areas of interest against which PPIs for selected proteins are displayed (by default on a cartoon of a cell). Annotations of localization are provided by the user or through our in-house database. The visualizer and server are written in JavaScript, making CellMap easy to customize and to extend by researchers and developers. PMID:29497493

Faraday's Principle and Air Travel in the Introductory Labs

Science.gov (United States)

Abdul-Razzaq, Wathiq; Thakur, Saikat Chakraborty

2017-01-01

We all know that we must improve the quality of teaching in science at all levels. Not only physicists but also many students from other areas of study take the introductory physics courses in college. Physics introductory laboratories (labs) can be one of the best tools to help these students understand applications of scientific principles that…

Web Interface Design Principles for Adults' Self-Directed Learning

Science.gov (United States)

Firat, Mehmet; Sakar, A. Nurhan; Kabakci Yurdakul, Isil

2016-01-01

One of the most important features which e-learning tools and environments must possess within the scope of lifelong learning is self-directed learning, which can be considered as a form of self-learning. The aim of this study was to determine, based on the views and recommendations of experts, interface design principles for the development of…

Dye laser principles with applications

CERN Document Server

Duarte, Frank J; Liao, Peter F; Kelley, Paul

1990-01-01

A tutorial introduction to the field of dye lasers, Dye Laser Principles also serves as an up-to-date overview for those using dye lasers as research and industrial tools. A number of the issues discussed in this book are pertinent not only to dye lasers but also to lasers in general. Most of the chapters in the book contain problem sets that expand on the material covered in the chapter.Key Features* Dye lasers are among the most versatile and successful laser sources currently available in use Offering both pulsed and continuous-wave operation and tunable from the near ultraviole

[Detection of protein-protein interactions by FRET and BRET methods].

Science.gov (United States)

Matoulková, E; Vojtěšek, B

2014-01-01

Nowadays, in vivo protein-protein interaction studies have become preferable detecting meth-ods that enable to show or specify (already known) protein interactions and discover their inhibitors. They also facilitate detection of protein conformational changes and discovery or specification of signaling pathways in living cells. One group of in vivo methods enabling these findings is based on fluorescent resonance energy transfer (FRET) and its bio-luminescent modification (BRET). They are based on visualization of protein-protein interactions via light or enzymatic excitation of fluorescent or bio-luminescent proteins. These methods allow not only protein localization within the cell or its organelles (or small animals) but they also allow us to quantify fluorescent signals and to discover weak or strong interaction partners. In this review, we explain the principles of FRET and BRET, their applications in the characterization of protein-protein interactions and we describe several findings using these two methods that clarify molecular and cellular mechanisms and signals related to cancer biology.

Identification of Protein-Protein Interactions with Glutathione-S-Transferase (GST) Fusion Proteins.

Science.gov (United States)

Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

2007-08-01

INTRODUCTIONGlutathione-S-transferase (GST) fusion proteins have had a wide range of applications since their introduction as tools for synthesis of recombinant proteins in bacteria. GST was originally selected as a fusion moiety because of several desirable properties. First and foremost, when expressed in bacteria alone, or as a fusion, GST is not sequestered in inclusion bodies (in contrast to previous fusion protein systems). Second, GST can be affinity-purified without denaturation because it binds to immobilized glutathione, which provides the basis for simple purification. Consequently, GST fusion proteins are routinely used for antibody generation and purification, protein-protein interaction studies, and biochemical analysis. This article describes the use of GST fusion proteins as probes for the identification of protein-protein interactions.

Globular and disordered – the non-identical twins in protein-protein interactions

Directory of Open Access Journals (Sweden)

Kaare eTeilum

2015-07-01

Full Text Available In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP’s bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol-1.

Sustaining Teamwork Behaviors Through Reinforcement of TeamSTEPPS Principles.

Science.gov (United States)

Lee, Soo-Hoon; Khanuja, Harpal S; Blanding, Renee J; Sedgwick, Jeanne; Pressimone, Kathleen; Ficke, James R; Jones, Lynne C

2017-10-30

Teamwork training improves short-term teamwork behaviors. However, improvements are often not sustained. The purpose of this study was to explore the extent to which teamwork reinforcement activities for orthopedic surgery teams lead to sustained teamwork behaviors. Seven months after 104 staff from an orthopedic surgical unit were trained in Team Strategies and Tools to Enhance Performance and Patient Safety principles, 4 reinforcement activities were implemented regarding leadership and communication: lectures with videos on leadership skills for nursing staff; an online self-paced learning program on communication skills for nursing staff; a 1-page summary on leadership skills e-mailed to surgical staff; and a 1-hour perioperative grand rounds on Team Strategies and Tools to Enhance Performance and Patient Safety principles for anesthesia staff and new staff. Twenty-four orthopedic surgical teams were evaluated on teamwork behaviors during surgery by 2 observers before and after the reinforcement period using the Observational Teamwork Assessment for Surgery tool. After reinforcement, leadership (P = 0.022) and communication (P = 0.044) behaviors improved compared with prereinforcement levels. Specifically, nursing staff improved in leadership (P = 0.016) and communication (P = 0.028) behaviors, surgical staff improved in leadership behaviors (P = 0.009), but anesthesia staff did not improve in any teamwork behaviors. Sustained improvement in teamwork behaviors requires reinforcement. Level III, prospective pre-post cohort study.

Public Choice, Market Failure, and Government Failure in Principles Textbooks

Science.gov (United States)

Fike, Rosemarie; Gwartney, James

2015-01-01

Public choice uses the tools of economics to analyze how the political process allocates resources and impacts economic activity. In this study, the authors examine twenty-three principles texts regarding coverage of public choice, market failure, and government failure. Approximately half the texts provide coverage of public choice and recognize…

Transient expression of green fluorescent protein in parasitic dodder as a tool for studying of cytoskeleton

Directory of Open Access Journals (Sweden)

Kaštier Peter

2017-06-01

Full Text Available Dodder (Cuscuta species cause severe agricultural damage in many countries throughout the world. To establish strategies for control of its growth and spreading it is important to study its life cycle and survival strategies. For these efforts genetic modification would represent a powerful tool. Here we report on Agrobacteriummediated transformation of dodder using green fluorescent protein (GFP fused to actin-binding protein as a vital marker. Since the shoot of germinating C. europaea contains a functional apical meristem and grows quickly comparing to the root-like structure, the shoot apex was used here as explant. The transgene expression was only transient, nevertheless it enabled to detect allocation of actin filaments and studying the cytoskeleton organization in dodder shoot apex. Transient expression of GFP appears to be a suitable method for studying Cuscuta development through cytoskeleton organisation that is presently largely unexplored.

Stochastic control theory dynamic programming principle

CERN Document Server

Nisio, Makiko

2015-01-01

This book offers a systematic introduction to the optimal stochastic control theory via the dynamic programming principle, which is a powerful tool to analyze control problems. First we consider completely observable control problems with finite horizons. Using a time discretization we construct a nonlinear semigroup related to the dynamic programming principle (DPP), whose generator provides the Hamilton–Jacobi–Bellman (HJB) equation, and we characterize the value function via the nonlinear semigroup, besides the viscosity solution theory. When we control not only the dynamics of a system but also the terminal time of its evolution, control-stopping problems arise. This problem is treated in the same frameworks, via the nonlinear semigroup. Its results are applicable to the American option price problem. Zero-sum two-player time-homogeneous stochastic differential games and viscosity solutions of the Isaacs equations arising from such games are studied via a nonlinear semigroup related to DPP (the min-ma...

WebScipio: An online tool for the determination of gene structures using protein sequences

Directory of Open Access Journals (Sweden)

Waack Stephan

2008-09-01

Full Text Available Abstract Background Obtaining the gene structure for a given protein encoding gene is an important step in many analyses. A software suited for this task should be readily accessible, accurate, easy to handle and should provide the user with a coherent representation of the most probable gene structure. It should be rigorous enough to optimise features on the level of single bases and at the same time flexible enough to allow for cross-species searches. Results WebScipio, a web interface to the Scipio software, allows a user to obtain the corresponding coding sequence structure of a here given a query protein sequence that belongs to an already assembled eukaryotic genome. The resulting gene structure is presented in various human readable formats like a schematic representation, and a detailed alignment of the query and the target sequence highlighting any discrepancies. WebScipio can also be used to identify and characterise the gene structures of homologs in related organisms. In addition, it offers a web service for integration with other programs. Conclusion WebScipio is a tool that allows users to get a high-quality gene structure prediction from a protein query. It offers more than 250 eukaryotic genomes that can be searched and produces predictions that are close to what can be achieved by manual annotation, for in-species and cross-species searches alike. WebScipio is freely accessible at http://www.webscipio.org.

HPASubC: A suite of tools for user subclassification of human protein atlas tissue images.

Science.gov (United States)

Cornish, Toby C; Chakravarti, Aravinda; Kapoor, Ashish; Halushka, Marc K

2015-01-01

The human protein atlas (HPA) is a powerful proteomic tool for visualizing the distribution of protein expression across most human tissues and many common malignancies. The HPA includes immunohistochemically-stained images from tissue microarrays (TMAs) that cover 48 tissue types and 20 common malignancies. The TMA data are used to provide expression information at the tissue, cellular, and occasionally, subcellular level. The HPA also provides subcellular data from confocal immunofluorescence data on three cell lines. Despite the availability of localization data, many unique patterns of cellular and subcellular expression are not documented. To get at this more granular data, we have developed a suite of Python scripts, HPASubC, to aid in subcellular, and cell-type specific classification of HPA images. This method allows the user to download and optimize specific HPA TMA images for review. Then, using a playstation-style video game controller, a trained observer can rapidly step through 10's of 1000's of images to identify patterns of interest. We have successfully used this method to identify 703 endothelial cell (EC) and/or smooth muscle cell (SMCs) specific proteins discovered within 49,200 heart TMA images. This list will assist us in subdividing cardiac gene or protein array data into expression by one of the predominant cell types of the myocardium: Myocytes, SMCs or ECs. The opportunity to further characterize unique staining patterns across a range of human tissues and malignancies will accelerate our understanding of disease processes and point to novel markers for tissue evaluation in surgical pathology.

HPASubC: A suite of tools for user subclassification of human protein atlas tissue images

Science.gov (United States)

Cornish, Toby C.; Chakravarti, Aravinda; Kapoor, Ashish; Halushka, Marc K.

2015-01-01

Background: The human protein atlas (HPA) is a powerful proteomic tool for visualizing the distribution of protein expression across most human tissues and many common malignancies. The HPA includes immunohistochemically-stained images from tissue microarrays (TMAs) that cover 48 tissue types and 20 common malignancies. The TMA data are used to provide expression information at the tissue, cellular, and occasionally, subcellular level. The HPA also provides subcellular data from confocal immunofluorescence data on three cell lines. Despite the availability of localization data, many unique patterns of cellular and subcellular expression are not documented. Materials and Methods: To get at this more granular data, we have developed a suite of Python scripts, HPASubC, to aid in subcellular, and cell-type specific classification of HPA images. This method allows the user to download and optimize specific HPA TMA images for review. Then, using a playstation-style video game controller, a trained observer can rapidly step through 10's of 1000's of images to identify patterns of interest. Results: We have successfully used this method to identify 703 endothelial cell (EC) and/or smooth muscle cell (SMCs) specific proteins discovered within 49,200 heart TMA images. This list will assist us in subdividing cardiac gene or protein array data into expression by one of the predominant cell types of the myocardium: Myocytes, SMCs or ECs. Conclusions: The opportunity to further characterize unique staining patterns across a range of human tissues and malignancies will accelerate our understanding of disease processes and point to novel markers for tissue evaluation in surgical pathology. PMID:26167380

Perceptions of Science Teachers on Implementation of Seven Principles for Good Practice in Education by Chickering and Gamson in Courses

Science.gov (United States)

Ugras, Mustafa; Asiltürk, Erol

2018-01-01

The present study aimed to determine the perceptions of science teachers on the implementation of the seven principles for good practice in education by Chickering and Gamson in their courses. Seven principles for good science education were used as a data collection tool in the survey. "The seven principles for good practice in science…

The application of the precautionary principle in practice: comparative dimensions

National Research Council Canada - National Science Library

Zander, Joakim

2010-01-01

... may lead to problems with the consistency, foreseeablility, effectiveness and efficiency of measures intended to reduce environmental or health risks. it is suggested that the precautionary principle indeed may be an important tool but in order to be acceptable it must be coupled with strong requirements on the performance of risk assessments...

Enhancing Formal Modelling Tool Support with Increased Automation

DEFF Research Database (Denmark)

Lausdahl, Kenneth

Progress report for the qualification exam report for PhD Student Kenneth Lausdahl. Initial work on enhancing tool support for the formal method VDM and the concept of unifying a abstract syntax tree with the ability for isolated extensions is described. The tool support includes a connection to ...... to UML and a test automation principle based on traces written as a kind of regular expressions....

Rationally designed synthetic protein hydrogels with predictable mechanical properties.

Science.gov (United States)

Wu, Junhua; Li, Pengfei; Dong, Chenling; Jiang, Heting; Bin Xue; Gao, Xiang; Qin, Meng; Wang, Wei; Bin Chen; Cao, Yi

2018-02-12

Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.

Teaching Practices in Principles of Economics Courses at Michigan Community Colleges.

Science.gov (United States)

Utech, Claudia J.; Mosti, Patricia A.

1995-01-01

Presents findings from a study of teaching practices in Principles of Economics courses at Michigan's 29 community colleges. Describes course prerequisites; textbooks used; lecture supplements; and the use of experiential learning tools, such as computers and field trips. Presents three recommendations for improving student preparation in…

CPdock: the complementarity plot for docking of proteins: implementing multi-dielectric continuum electrostatics.

Science.gov (United States)

Basu, Sankar

2017-12-07

The complementarity plot (CP) is an established validation tool for protein structures, applicable to both globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (S m , E m ) for amino acid side-chains buried within the protein interior or interface and plots them in a two-dimensional plot having knowledge-based probabilistic quality estimates for the residues as well as for the whole structure. The current report essentially presents an upgraded version of the plot with the implementation of the advanced multi-dielectric functionality (as in Delphi version 6.2 or higher) in the computation of electrostatic complementarity to make the validation tool physico-chemically more realistic. The two methods (single- and multi-dielectric) agree decently in their resultant E m values, and hence, provisions for both methods have been kept in the software suite. So to speak, the global electrostatic balance within a well-folded protein and/or a well-packed interface seems only marginally perturbed by the choice of different internal dielectric values. However, both from theoretical as well as practical grounds, the more advanced multi-dielectric version of the plot is certainly recommended for potentially producing more reliable results. The report also presents a new methodology and a variant plot, namely CP dock , based on the same principles of complementarity specifically designed to be used in the docking of proteins. The efficacy of the method to discriminate between good and bad docked protein complexes has been tested on a recent state-of-the-art docking benchmark. The results unambiguously indicate that CP dock can indeed be effective in the initial screening phase of a docking scoring pipeline before going into more sophisticated and computationally expensive scoring functions. CP dock has been made available at https://github.com/nemo8130/CPdock . Graphical Abstract An example showing

Applying Pragmatics Principles for Interaction with Visual Analytics.

Science.gov (United States)

Hoque, Enamul; Setlur, Vidya; Tory, Melanie; Dykeman, Isaac

2018-01-01

Interactive visual data analysis is most productive when users can focus on answering the questions they have about their data, rather than focusing on how to operate the interface to the analysis tool. One viable approach to engaging users in interactive conversations with their data is a natural language interface to visualizations. These interfaces have the potential to be both more expressive and more accessible than other interaction paradigms. We explore how principles from language pragmatics can be applied to the flow of visual analytical conversations, using natural language as an input modality. We evaluate the effectiveness of pragmatics support in our system Evizeon, and present design considerations for conversation interfaces to visual analytics tools.

BMRF-Net: a software tool for identification of protein interaction subnetworks by a bagging Markov random field-based method.

Science.gov (United States)

Shi, Xu; Barnes, Robert O; Chen, Li; Shajahan-Haq, Ayesha N; Hilakivi-Clarke, Leena; Clarke, Robert; Wang, Yue; Xuan, Jianhua

2015-07-15

Identification of protein interaction subnetworks is an important step to help us understand complex molecular mechanisms in cancer. In this paper, we develop a BMRF-Net package, implemented in Java and C++, to identify protein interaction subnetworks based on a bagging Markov random field (BMRF) framework. By integrating gene expression data and protein-protein interaction data, this software tool can be used to identify biologically meaningful subnetworks. A user friendly graphic user interface is developed as a Cytoscape plugin for the BMRF-Net software to deal with the input/output interface. The detailed structure of the identified networks can be visualized in Cytoscape conveniently. The BMRF-Net package has been applied to breast cancer data to identify significant subnetworks related to breast cancer recurrence. The BMRF-Net package is available at http://sourceforge.net/projects/bmrfcjava/. The package is tested under Ubuntu 12.04 (64-bit), Java 7, glibc 2.15 and Cytoscape 3.1.0. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Using Green Chemistry and Engineering Principles to Design ...

Science.gov (United States)

The concepts of green chemistry and engineering (GC&E) have been promoted as an effective qualitative framework for developing more sustainable chemical syntheses, processes, and material management techniques. This has been demonstrated by many theoretical and practical cases. In addition, there are several approaches and frameworks focused on demonstrating that improvements were achieved through GC&E technologies. However, the application of these principles is not always straightforward. We propose using systematic frameworks and tools that help practitioners when deciding which principles can be applied, the levels of implementation, prospective of obtaining simultaneous improvements in all sustainability aspects, and ways to deal with multiobjective problems. Therefore, this contribution aims to provide a systematic combination of three different and complementary design tools for assisting designers in evaluating, developing, and improving chemical manufacturing and material management systems under GC&E perspectives. The WAR Algorithm, GREENSCOPE, and SustainPro were employed for this synergistic approach of incorporating sustainability at early stages of process development. In this demonstration, simulated ammonia production is used as a case study to illustrate this advancement. Results show how to identify process design areas for improvements, key factors, multi-criteria decision-making solutions, and optimal tradeoffs. Finally, conclusions were pre

Quantifying system safety: A comparison of the SBOAT & Safety Barrier Manager tools

DEFF Research Database (Denmark)

Hansen, Zaza Nadja Lee; Duijm, Nijs Jan; Markert, Frank

2015-01-01

This paper presents two software tools for analyzing safety risks, SBOAT (Stochastic BPMN Optimisation and Analysis Tool) and SBM (SafetyBarrierManagerr). SBOAT employs principles from stochastic model checking to allow for the quantitative verification of workflows. SBM supports the creation...

MetalS2: a tool for the structural alignment of minimal functional sites in metal-binding proteins and nucleic acids.

Science.gov (United States)

Andreini, Claudia; Cavallaro, Gabriele; Rosato, Antonio; Valasatava, Yana

2013-11-25

We developed a new software tool, MetalS(2), for the structural alignment of Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. Such local environment has a determinant role in tuning the chemical reactivity of the metal, ultimately contributing to the functional properties of the whole system. On our example data sets, MetalS(2) unveiled structural similarities that other programs for protein structure comparison do not consistently point out and overall identified a larger number of structurally similar MFSs. MetalS(2) supports the comparison of MFSs harboring different metals and/or with different nuclearity and is available both as a stand-alone program and a Web tool ( http://metalweb.cerm.unifi.it/tools/metals2/).

Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction

Science.gov (United States)

Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

2015-01-01

Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process. PMID:26393507

The gauge principle vs. the equivalence principle

International Nuclear Information System (INIS)

Gates, S.J. Jr.

1984-01-01

Within the context of field theory, it is argued that the role of the equivalence principle may be replaced by the principle of gauge invariance to provide a logical framework for theories of gravitation

MANAGER PRINCIPLES AS BASIS OF MANAGEMENT STYLE TRANSFORMATION

OpenAIRE

R. A. Kopytov

2011-01-01

The paper considers an approach which is based on non-conventional mechanisms of management style formation. The preset level of sustainable management is maintained by self-organized environment created in the process of management style transformation in efficient management principles. Their efficiency is checked within an adaptive algorithm. The algorithm is developed on the basis of combination of evaluative tools  and base of operational  proves. The operating algorithm capability is te...

HPASubC: A suite of tools for user subclassification of human protein atlas tissue images

Directory of Open Access Journals (Sweden)

Toby C Cornish

2015-01-01

Full Text Available Background: The human protein atlas (HPA is a powerful proteomic tool for visualizing the distribution of protein expression across most human tissues and many common malignancies. The HPA includes immunohistochemically-stained images from tissue microarrays (TMAs that cover 48 tissue types and 20 common malignancies. The TMA data are used to provide expression information at the tissue, cellular, and occasionally, subcellular level. The HPA also provides subcellular data from confocal immunofluorescence data on three cell lines. Despite the availability of localization data, many unique patterns of cellular and subcellular expression are not documented. Materials and Methods: To get at this more granular data, we have developed a suite of Python scripts, HPASubC, to aid in subcellular, and cell-type specific classification of HPA images. This method allows the user to download and optimize specific HPA TMA images for review. Then, using a playstation-style video game controller, a trained observer can rapidly step through 10′s of 1000′s of images to identify patterns of interest. Results: We have successfully used this method to identify 703 endothelial cell (EC and/or smooth muscle cell (SMCs specific proteins discovered within 49,200 heart TMA images. This list will assist us in subdividing cardiac gene or protein array data into expression by one of the predominant cell types of the myocardium: Myocytes, SMCs or ECs. Conclusions: The opportunity to further characterize unique staining patterns across a range of human tissues and malignancies will accelerate our understanding of disease processes and point to novel markers for tissue evaluation in surgical pathology.

Protein-Protein Docking in Drug Design and Discovery.

Science.gov (United States)

Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

2018-01-01

Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

GalaxyDock BP2 score: a hybrid scoring function for accurate protein-ligand docking

Science.gov (United States)

Baek, Minkyung; Shin, Woong-Hee; Chung, Hwan Won; Seok, Chaok

2017-07-01

Protein-ligand docking is a useful tool for providing atomic-level understanding of protein functions in nature and design principles for artificial ligands or proteins with desired properties. The ability to identify the true binding pose of a ligand to a target protein among numerous possible candidate poses is an essential requirement for successful protein-ligand docking. Many previously developed docking scoring functions were trained to reproduce experimental binding affinities and were also used for scoring binding poses. However, in this study, we developed a new docking scoring function, called GalaxyDock BP2 Score, by directly training the scoring power of binding poses. This function is a hybrid of physics-based, empirical, and knowledge-based score terms that are balanced to strengthen the advantages of each component. The performance of the new scoring function exhibits significant improvement over existing scoring functions in decoy pose discrimination tests. In addition, when the score is used with the GalaxyDock2 protein-ligand docking program, it outperformed other state-of-the-art docking programs in docking tests on the Astex diverse set, the Cross2009 benchmark set, and the Astex non-native set. GalaxyDock BP2 Score and GalaxyDock2 with this score are freely available at http://galaxy.seoklab.org/softwares/galaxydock.html.

Dialysis Malnutrition and Malnutrition Inflammation Scores: screening tools for prediction of dialysis-related protein-energy wasting in Malaysia.

Science.gov (United States)

Harvinder, Gilcharan Singh; Swee, Winnie Chee Siew; Karupaiah, Tilakavati; Sahathevan, Sharmela; Chinna, Karuthan; Ahmad, Ghazali; Bavanandan, Sunita; Goh, Bak Leong

2016-01-01

Malnutrition is highly prevalent in Malaysian dialysis patients and there is a need for a valid screening tool for early identification and management. This cross-sectional study aims to examine the sensitivity of the Dialysis Malnutrition Score (DMS) and Malnutrition Inflammation Score (MIS) tools in predicting protein-energy wasting (PEW) among Malaysian dialysis patients. A total of 155 haemodialysis (HD) and 90 peritoneal dialysis (PD) patients were screened for risk of malnutrition using DMS and MIS and comparisons were made with established guidelines by International Society of Renal Nutrition and Metabolism (ISRNM) for PEW. MIS cut-off score of >=5 indicated presence of malnutrition in all patients. A total of 59% of HD and 83% of PD patients had PEW by ISRNM criteria. Based on DMS, 73% of HD and 71% of PD patients exhibited moderate malnutrition, whilst using MIS, 88% and 90%, respectively were malnourished. DMS and MIS correlated significantly in HD (r2=0.552, pmalnutrition classification were established (score >=5) for use amongst Malaysian dialysis patients. Both DMS and MIS are valid tools to be used for nutrition screening of dialysis patients especially those undergoing peritoneal dialysis. The DMS may be a more practical and simpler tool to be utilized in the Malaysian dialysis settings as it does not require laboratory markers.

Achieving Integration in Mixed Methods Designs—Principles and Practices

OpenAIRE

Fetters, Michael D; Curry, Leslie A; Creswell, John W

2013-01-01

Mixed methods research offers powerful tools for investigating complex processes and systems in health and health care. This article describes integration principles and practices at three levels in mixed methods research and provides illustrative examples. Integration at the study design level occurs through three basic mixed method designs—exploratory sequential, explanatory sequential, and convergent—and through four advanced frameworks—multistage, intervention, case study, and participato...

Why the Central Dogma: on the nature of the great biological exclusion principle.

Science.gov (United States)

Koonin, Eugene V

2015-09-16

The Central Dogma of molecular biology posits that transfer of information from proteins back to nucleic acids does not occur in biological systems. I argue that the impossibility of reverse translation is indeed a major, physical exclusion principle that emerges due to the transition from the digital information carriers, nucleic acids, to analog information carriers, proteins, which involves irreversible suppression of the digital information.

E-LEARNING TOOLS: STRUCTURE, CONTENT, CLASSIFICATION

Directory of Open Access Journals (Sweden)

Yuliya H. Loboda

2012-05-01

Full Text Available The article analyses the problems of organization of educational process with use of electronic means of education. Specifies the definition of "electronic learning", their structure and content. Didactic principles are considered, which are the basis of their creation and use. Given the detailed characteristics of e-learning tools for methodological purposes. On the basis of the allocated pedagogical problems of the use of electronic means of education presented and complemented by their classification, namely the means of theoretical and technological training, means of practical training, support tools, and comprehensive facilities.

Toxic release consequence analysis tool (TORCAT) for inherently safer design plant

International Nuclear Information System (INIS)

Shariff, Azmi Mohd; Zaini, Dzulkarnain

2010-01-01

Many major accidents due to toxic release in the past have caused many fatalities such as the tragedy of MIC release in Bhopal, India (1984). One of the approaches is to use inherently safer design technique that utilizes inherent safety principle to eliminate or minimize accidents rather than to control the hazard. This technique is best implemented in preliminary design stage where the consequence of toxic release can be evaluated and necessary design improvements can be implemented to eliminate or minimize the accidents to as low as reasonably practicable (ALARP) without resorting to costly protective system. However, currently there is no commercial tool available that has such capability. This paper reports on the preliminary findings on the development of a prototype tool for consequence analysis and design improvement via inherent safety principle by utilizing an integrated process design simulator with toxic release consequence analysis model. The consequence analysis based on the worst-case scenarios during process flowsheeting stage were conducted as case studies. The preliminary finding shows that toxic release consequences analysis tool (TORCAT) has capability to eliminate or minimize the potential toxic release accidents by adopting the inherent safety principle early in preliminary design stage.

Radio frequency transistors principles and practical applications

CERN Document Server

Dye, Norm

1993-01-01

Cellular telephones, satellite communications and radar systems are adding to the increasing demand for radio frequency circuit design principles. At the same time, several generations of digitally-oriented graduates are missing the essential RF skills. This book contains a wealth of valuable design information difficult to find elsewhere.It's a complete 'tool kit' for successful RF circuit design. Written by experienced RF design engineers from Motorola's semiconductors product section.Book covers design examples of circuits (e.g. amplifiers; oscillators; switches; pulsed power; modular syst

FDTD simulation tools for UWB antenna analysis.

Energy Technology Data Exchange (ETDEWEB)

Brocato, Robert Wesley

2005-02-01

This paper describes the development of a set of software tools useful for analyzing ultra-wideband (UWB) antennas and structures. These tools are used to perform finite difference time domain (FDTD) simulation of a conical antenna with continuous wave (CW) and UWB pulsed excitations. The antenna is analyzed using spherical coordinate-based FDTD equations that are derived from first principles. The simulation results for CW excitation are compared to simulation and measured results from published sources; the results for UWB excitation are new.

FDTD simulation tools for UWB antenna analysis.

Energy Technology Data Exchange (ETDEWEB)

Brocato, Robert Wesley

2004-12-01

This paper describes the development of a set of software tools useful for analyzing ultra-wideband (UWB) antennas and structures. These tools are used to perform finite difference time domain (FDTD) simulation of a conical antenna with continuous wave (CW) and UWB pulsed excitations. The antenna is analyzed using spherical coordinate-based FDTD equations that are derived from first principles. The simulation results for CW excitation are compared to simulation and measured results from published sources; the results for UWB excitation are new.

Design of jigs, fixtures and press tools

CERN Document Server

Venkataraman, K

2015-01-01

Textbook presenting the fundamentals of tool design with special focus on jigs, fixtures and die design Covers sections on sheet metal forming processes; turning, grinding, broaching, welding and modular fixtures; principles of clamping; and an Introduction to Presses and Auxiliary Equipment Author has many years' experience in both academic and industrial environments, and presents this work in an easily-accessible style End of chapter questions and answers assist the learning process for both practicing tooling designers and engineers, and manufacturing en

PDB-Explorer: a web-based interactive map of the protein data bank in shape space.

Science.gov (United States)

Jin, Xian; Awale, Mahendra; Zasso, Michaël; Kostro, Daniel; Patiny, Luc; Reymond, Jean-Louis

2015-10-23

The RCSB Protein Data Bank (PDB) provides public access to experimentally determined 3D-structures of biological macromolecules (proteins, peptides and nucleic acids). While various tools are available to explore the PDB, options to access the global structural diversity of the entire PDB and to perceive relationships between PDB structures remain very limited. A 136-dimensional atom pair 3D-fingerprint for proteins (3DP) counting categorized atom pairs at increasing through-space distances was designed to represent the molecular shape of PDB-entries. Nearest neighbor searches examples were reported exemplifying the ability of 3DP-similarity to identify closely related biomolecules from small peptides to enzyme and large multiprotein complexes such as virus particles. The principle component analysis was used to obtain the visualization of PDB in 3DP-space. The 3DP property space groups proteins and protein assemblies according to their 3D-shape similarity, yet shows exquisite ability to distinguish between closely related structures. An interactive website called PDB-Explorer is presented featuring a color-coded interactive map of PDB in 3DP-space. Each pixel of the map contains one or more PDB-entries which are directly visualized as ribbon diagrams when the pixel is selected. The PDB-Explorer website allows performing 3DP-nearest neighbor searches of any PDB-entry or of any structure uploaded as protein-type PDB file. All functionalities on the website are implemented in JavaScript in a platform-independent manner and draw data from a server that is updated daily with the latest PDB additions, ensuring complete and up-to-date coverage. The essentially instantaneous 3DP-similarity search with the PDB-Explorer provides results comparable to those of much slower 3D-alignment algorithms, and automatically clusters proteins from the same superfamilies in tight groups. A chemical space classification of PDB based on molecular shape was obtained using a new atom-pair 3

Scleroglucan-borax hydrogel: a flexible tool for redox protein immobilization.

Science.gov (United States)

Frasconi, Marco; Rea, Sara; Matricardi, Pietro; Favero, Gabriele; Mazzei, Franco

2009-09-15

A highly stable biological film was prepared by casting an aqueous dispersion of protein and composite hydrogel obtained from the polysaccharide Scleroglucan (Sclg) and borax as a cross-linking agent. Heme proteins, such as hemoglobin (Hb), myoglobin (Mb), and horseradish peroxidase (HRP), were chosen as model proteins to investigate the immobilized system. A pair of well-defined quasi-reversible redox peaks, characteristics of the protein heme FeII/FeIII redox couples, were obtained at the Sclg-borax/proteins films on pyrolytic graphite (PG) electrodes, as a consequence of the direct electron transfer between the protein and the PG electrode. A full characterization of the electron transfer kinetic was performed by opportunely modeling data obtained from cyclic voltammetry and square wave voltammetry experiments. The efficiency of our cross-linking approach was investigated by studying the influence of different borax groups percentage in the Sclg matrix, revealing the versatility of this hydrogel in the immobilization of redox proteins. The native conformation of the three heme proteins entrapped in the hydrogel films were proved to be unchanged, reflected by the unaltered Soret adsorption band and by the catalytic activity toward hydrogen peroxide (H2O2). The main kinetic parameters, such as the apparent Michaelis-Menten constant, for the electrocatalytic reaction were also evaluated. The peculiar characteristics of Sclg-borax matrix make it possible to find wide opportunities as proteins immobilizing agent for studies of direct electrochemistry and biosensors development.

Biomimetics approach for methods to release microobjects from the gripping tool

DEFF Research Database (Denmark)

Gegeckaite, Asta; Moon, Jack; Hansen, Hans Nørgaard

2005-01-01

of handling can be found in for example insect everyday life, cells, enzymes etc. To find out these principles we need special tools, like BioDlab database, which is created specially to find the examples form the biology in order to solve engineering problems. In this report different principles of handling...... at the micro and nano level are presented as well as solutions for micro assembly principles are introduced, concentrating on the adhesion and releasing during the picking and releasing stages of the handling scenario....

Development and use of an application as a tool in biochemistry teaching: carbohydrates, lipids, proteins and nucleic acids

Directory of Open Access Journals (Sweden)

Nayra Rodrigues de Alcântara

2015-12-01

Full Text Available This study aimed to produce an app with information contextualized and creative on the biomolecules: carbohydrates, lipids, proteins, and nucleic acids for can be used as a support tool to professor of biochemistry, biology and science. The research was divided into three stages: the first stage questionnaires were applied to verify the level of knowledge of participants; the second stage was the preparation of the app and, after contact of the students with the app, the same questionnaire was completed again to verify the effectiveness of the methodology; the third stage was to analyze the result.. The application has ratings of biomolecules, definitions, functions and curiosities to the peoples to use the app and can relate biochemistry with their daily lives. The BQB Tech application was efficient to be used as tools in biochemistry teaching.

Why the Central Dogma: on the nature of the great biological exclusion principle

OpenAIRE

Koonin, Eugene V.

2015-01-01

Abstract The Central Dogma of molecular biology posits that transfer of information from proteins back to nucleic acids does not occur in biological systems. I argue that the impossibility of reverse translation is indeed a major, physical exclusion principle that emerges due to the transition from the digital information carriers, nucleic acids, to analog information carriers, proteins, which involves irreversible suppression of the digital information. Reviewers This article was reviewed by...

Novel Technology for Protein-Protein Interaction-based Targeted Drug Discovery

Directory of Open Access Journals (Sweden)

Jung Me Hwang

2011-12-01

Full Text Available We have developed a simple but highly efficient in-cell protein-protein interaction (PPI discovery system based on the translocation properties of protein kinase C- and its C1a domain in live cells. This system allows the visual detection of trimeric and dimeric protein interactions including cytosolic, nuclear, and/or membrane proteins with their cognate ligands. In addition, this system can be used to identify pharmacological small compounds that inhibit specific PPIs. These properties make this PPI system an attractive tool for screening drug candidates and mapping the protein interactome.

ASAView: Database and tool for solvent accessibility representation in proteins

Directory of Open Access Journals (Sweden)

Fawareh Hamed

2004-05-01

Full Text Available Abstract Background Accessible surface area (ASA or solvent accessibility of amino acids in a protein has important implications. Knowledge of surface residues helps in locating potential candidates of active sites. Therefore, a method to quickly see the surface residues in a two dimensional model would help to immediately understand the population of amino acid residues on the surface and in the inner core of the proteins. Results ASAView is an algorithm, an application and a database of schematic representations of solvent accessibility of amino acid residues within proteins. A characteristic two-dimensional spiral plot of solvent accessibility provides a convenient graphical view of residues in terms of their exposed surface areas. In addition, sequential plots in the form of bar charts are also provided. Online plots of the proteins included in the entire Protein Data Bank (PDB, are provided for the entire protein as well as their chains separately. Conclusions These graphical plots of solvent accessibility are likely to provide a quick view of the overall topological distribution of residues in proteins. Chain-wise computation of solvent accessibility is also provided.

Principles and equations for measuring and interpreting protein stability: From monomer to tetramer.

Science.gov (United States)

Bedouelle, Hugues

2016-02-01

The ability to measure the thermodynamic stability of proteins with precision is important for both academic and applied research. Such measurements rely on mathematical models of the protein denaturation profile, i.e. the relation between a global protein signal, corresponding to the folding states in equilibrium, and the variable value of a denaturing agent, either heat or a chemical molecule, e.g. urea or guanidinium hydrochloride. In turn, such models rely on a handful of physical laws: the laws of mass action and conservation, the law that relates the protein signal and concentration, and the one that relates stability and denaturant value. So far, equations have been derived mainly for the denaturation profiles of homomeric proteins. Here, we review the underlying basic physical laws and show in detail how to derive model equations for the unfolding equilibria of homomeric or heteromeric proteins up to trimers and potentially tetramers, with or without folding intermediates, and give full demonstrations. We show that such equations cannot be derived for pentamers or higher oligomers except in special degenerate cases. We expand the method to signals that do not correspond to extensive protein properties. We review and expand methods for uncovering hidden intermediates of unfolding. Finally, we review methods for comparing and interpreting the thermodynamic parameters that derive from stability measurements for cognate wild-type and mutant proteins. This work should provide a robust theoretical basis for measuring the stability of complex proteins. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Principles of Mechanical Excavation

International Nuclear Information System (INIS)

Lislerud, A.

1997-12-01

Mechanical excavation of rock today includes several methods such as tunnel boring, raiseboring, roadheading and various continuous mining systems. Of these raiseboring is one potential technique for excavating shafts in the repository for spent nuclear fuel and dry blind boring is promising technique for excavation of deposition holes, as demonstrated in the Research Tunnel at Olkiluoto. In addition, there is potential for use of other mechanical excavation techniques in different parts of the repository. One of the main objectives of this study was to analyze the factors which affect the feasibility of mechanical rock excavation in hard rock conditions and to enhance the understanding of factors which affect rock cutting so as to provide an improved basis for excavator performance prediction modeling. The study included the following four main topics: (a) phenomenological model based on similarity analysis for roller disk cutting, (b) rock mass properties which affect rock cuttability and tool life, (c) principles for linear and field cutting tests and performance prediction modeling and (d) cutter head lacing design procedures and principles. As a conclusion of this study, a test rig was constructed, field tests were planned and started up. The results of the study can be used to improve the performance prediction models used to assess the feasibility of different mechanical excavation techniques at various repository investigation sites. (orig.)

Principles of Mechanical Excavation

Energy Technology Data Exchange (ETDEWEB)

Lislerud, A. [Tamrock Corp., Tampere (Finland)

1997-12-01

Mechanical excavation of rock today includes several methods such as tunnel boring, raiseboring, roadheading and various continuous mining systems. Of these raiseboring is one potential technique for excavating shafts in the repository for spent nuclear fuel and dry blind boring is promising technique for excavation of deposition holes, as demonstrated in the Research Tunnel at Olkiluoto. In addition, there is potential for use of other mechanical excavation techniques in different parts of the repository. One of the main objectives of this study was to analyze the factors which affect the feasibility of mechanical rock excavation in hard rock conditions and to enhance the understanding of factors which affect rock cutting so as to provide an improved basis for excavator performance prediction modeling. The study included the following four main topics: (a) phenomenological model based on similarity analysis for roller disk cutting, (b) rock mass properties which affect rock cuttability and tool life, (c) principles for linear and field cutting tests and performance prediction modeling and (d) cutter head lacing design procedures and principles. As a conclusion of this study, a test rig was constructed, field tests were planned and started up. The results of the study can be used to improve the performance prediction models used to assess the feasibility of different mechanical excavation techniques at various repository investigation sites. (orig.). 21 refs.

Data management of protein interaction networks

CERN Document Server

Cannataro, Mario

2012-01-01

Interactomics: a complete survey from data generation to knowledge extraction With the increasing use of high-throughput experimental assays, more and more protein interaction databases are becoming available. As a result, computational analysis of protein-to-protein interaction (PPI) data and networks, now known as interactomics, has become an essential tool to determine functionally associated proteins. From wet lab technologies to data management to knowledge extraction, this timely book guides readers through the new science of interactomics, giving them the tools needed to: Generate

A Demonstration of Le Chatelier’s Principle on the Nanoscale

Science.gov (United States)

2017-01-01

Photothermal desorption of molecules from plasmonic nanoparticles is an example of a light-triggered molecular release due to heating of the system. However, this phenomenon ought to work only if the molecule–nanoparticle interaction is exothermic in nature. In this study, we compare protein adsorption behavior onto gold nanoparticles for both endothermic and exothermic complexation reactions, and demonstrate that Le Chatelier’s principle can be applied to predict protein adsorption or desorption on nanomaterial surfaces. Polyelectrolyte-wrapped gold nanorods were used as adsorption platforms for two different proteins, which we were able to adsorb/desorb from the nanorod surface depending on the thermodynamics of their interactions. Furthermore, we show that the behaviors hold up under more complex biological environments such as fetal bovine serum. PMID:29104926

Postmortem muscle protein degradation in humans as a tool for PMI delimitation.

Science.gov (United States)

Pittner, Stefan; Ehrenfellner, Bianca; Monticelli, Fabio C; Zissler, Angela; Sänger, Alexandra M; Stoiber, Walter; Steinbacher, Peter

2016-11-01

Forensic estimation of time since death relies on diverse approaches, including measurement and comparison of environmental and body core temperature and analysis of insect colonization on a dead body. However, most of the applied methods have practical limitations or provide insufficient results under certain circumstances. Thus, new methods that can easily be implemented into forensic routine work are required to deliver more and discrete information about the postmortem interval (PMI). Following a previous work on skeletal muscle degradation in the porcine model, we analyzed human postmortem skeletal muscle samples of 40 forensic cases by Western blotting and casein zymography. Our results demonstrate predictable protein degradation processes in human muscle that are distinctly associated with temperature and the PMI. We provide information on promising degradation markers for certain periods of time postmortem, which can be useful tools for time since death delimitation. In addition, we discuss external influencing factors such as age, body mass index, sex, and cause of death that need to be considered in future routine application of the method in humans.

Controlling proteins through molecular springs.

Science.gov (United States)

Zocchi, Giovanni

2009-01-01

We argue that the mechanical control of proteins-the notion of controlling chemical reactions and processes by mechanics-is conceptually interesting. We give a brief review of the main accomplishments so far, leading to our present approach of using DNA molecular springs to exert controlled stresses on proteins. Our focus is on the physical principles that underlie both artificial mechanochemical devices and natural mechanisms of allostery.

Expanding Uncertainty Principle to Certainty-Uncertainty Principles with Neutrosophy and Quad-stage Method

Directory of Open Access Journals (Sweden)

Fu Yuhua

2015-03-01

Full Text Available The most famous contribution of Heisenberg is uncertainty principle. But the original uncertainty principle is improper. Considering all the possible situations (including the case that people can create laws and applying Neutrosophy and Quad-stage Method, this paper presents "certainty-uncertainty principles" with general form and variable dimension fractal form. According to the classification of Neutrosophy, "certainty-uncertainty principles" can be divided into three principles in different conditions: "certainty principle", namely a particle’s position and momentum can be known simultaneously; "uncertainty principle", namely a particle’s position and momentum cannot be known simultaneously; and neutral (fuzzy "indeterminacy principle", namely whether or not a particle’s position and momentum can be known simultaneously is undetermined. The special cases of "certain ty-uncertainty principles" include the original uncertainty principle and Ozawa inequality. In addition, in accordance with the original uncertainty principle, discussing high-speed particle’s speed and track with Newton mechanics is unreasonable; but according to "certaintyuncertainty principles", Newton mechanics can be used to discuss the problem of gravitational defection of a photon orbit around the Sun (it gives the same result of deflection angle as given by general relativity. Finally, for the reason that in physics the principles, laws and the like that are regardless of the principle (law of conservation of energy may be invalid; therefore "certaintyuncertainty principles" should be restricted (or constrained by principle (law of conservation of energy, and thus it can satisfy the principle (law of conservation of energy.

Visualization portal for genetic variation (VizGVar): a tool for interactive visualization of SNPs and somatic mutations in exons, genes and protein domains.

Science.gov (United States)

Solano-Román, Antonio; Alfaro-Arias, Verónica; Cruz-Castillo, Carlos; Orozco-Solano, Allan

2018-03-15

VizGVar was designed to meet the growing need of the research community for improved genomic and proteomic data viewers that benefit from better information visualization. We implemented a new information architecture and applied user centered design principles to provide a new improved way of visualizing genetic information and protein data related to human disease. VizGVar connects the entire database of Ensembl protein motifs, domains, genes and exons with annotated SNPs and somatic variations from PharmGKB and COSMIC. VizGVar precisely represents genetic variations and their respective location by colored curves to designate different types of variations. The structured hierarchy of biological data is reflected in aggregated patterns through different levels, integrating several layers of information at once. VizGVar provides a new interactive, web-based JavaScript visualization of somatic mutations and protein variation, enabling fast and easy discovery of clinically relevant variation patterns. VizGVar is accessible at http://vizport.io/vizgvar; http://vizport.io/vizgvar/doc/. asolano@broadinstitute.org or allan.orozcosolano@ucr.ac.cr.

HDAPD: a web tool for searching the disease-associated protein structures

Science.gov (United States)

2010-01-01

Background The protein structures of the disease-associated proteins are important for proceeding with the structure-based drug design to against a particular disease. Up until now, proteins structures are usually searched through a PDB id or some sequence information. However, in the HDAPD database presented here the protein structure of a disease-associated protein can be directly searched through the associated disease name keyed in. Description The search in HDAPD can be easily initiated by keying some key words of a disease, protein name, protein type, or PDB id. The protein sequence can be presented in FASTA format and directly copied for a BLAST search. HDAPD is also interfaced with Jmol so that users can observe and operate a protein structure with Jmol. The gene ontological data such as cellular components, molecular functions, and biological processes are provided once a hyperlink to Gene Ontology (GO) is clicked. Further, HDAPD provides a link to the KEGG map such that where the protein is placed and its relationship with other proteins in a metabolic pathway can be found from the map. The latest literatures namely titles, journals, authors, and abstracts searched from PubMed for the protein are also presented as a length controllable list. Conclusions Since the HDAPD data content can be routinely updated through a PHP-MySQL web page built, the new database presented is useful for searching the structures for some disease-associated proteins that may play important roles in the disease developing process for performing the structure-based drug design to against the diseases. PMID:20158919

Quantifying the molecular origins of opposite solvent effects on protein-protein interactions.

Directory of Open Access Journals (Sweden)

Vincent Vagenende

Full Text Available Although the nature of solvent-protein interactions is generally weak and non-specific, addition of cosolvents such as denaturants and osmolytes strengthens protein-protein interactions for some proteins, whereas it weakens protein-protein interactions for others. This is exemplified by the puzzling observation that addition of glycerol oppositely affects the association constants of two antibodies, D1.3 and D44.1, with lysozyme. To resolve this conundrum, we develop a methodology based on the thermodynamic principles of preferential interaction theory and the quantitative characterization of local protein solvation from molecular dynamics simulations. We find that changes of preferential solvent interactions at the protein-protein interface quantitatively account for the opposite effects of glycerol on the antibody-antigen association constants. Detailed characterization of local protein solvation in the free and associated protein states reveals how opposite solvent effects on protein-protein interactions depend on the extent of dewetting of the protein-protein contact region and on structural changes that alter cooperative solvent-protein interactions at the periphery of the protein-protein interface. These results demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions, and establish a general methodology for predicting and understanding solvent effects on protein-protein interactions in diverse biological environments.

MannDB – A microbial database of automated protein sequence analyses and evidence integration for protein characterization

Directory of Open Access Journals (Sweden)

Kuczmarski Thomas A

2006-10-01

Full Text Available Abstract Background MannDB was created to meet a need for rapid, comprehensive automated protein sequence analyses to support selection of proteins suitable as targets for driving the development of reagents for pathogen or protein toxin detection. Because a large number of open-source tools were needed, it was necessary to produce a software system to scale the computations for whole-proteome analysis. Thus, we built a fully automated system for executing software tools and for storage, integration, and display of automated protein sequence analysis and annotation data. Description MannDB is a relational database that organizes data resulting from fully automated, high-throughput protein-sequence analyses using open-source tools. Types of analyses provided include predictions of cleavage, chemical properties, classification, features, functional assignment, post-translational modifications, motifs, antigenicity, and secondary structure. Proteomes (lists of hypothetical and known proteins are downloaded and parsed from Genbank and then inserted into MannDB, and annotations from SwissProt are downloaded when identifiers are found in the Genbank entry or when identical sequences are identified. Currently 36 open-source tools are run against MannDB protein sequences either on local systems or by means of batch submission to external servers. In addition, BLAST against protein entries in MvirDB, our database of microbial virulence factors, is performed. A web client browser enables viewing of computational results and downloaded annotations, and a query tool enables structured and free-text search capabilities. When available, links to external databases, including MvirDB, are provided. MannDB contains whole-proteome analyses for at least one representative organism from each category of biological threat organism listed by APHIS, CDC, HHS, NIAID, USDA, USFDA, and WHO. Conclusion MannDB comprises a large number of genomes and comprehensive protein

The Principle of the Presumption of Innocence and its Challenges in ...

African Journals Online (AJOL)

The administration of the criminal justice system tries to strike a balance between the search for truth and the fairness of the process. To this end, the law should protect individual rights and impose various legal burdens on the state. One such tool is the principle of the presumption of innocence until proven guilty. This is a ...

Some principles of automated control systems construction with project organizational structure

OpenAIRE

Kovalenko, Ihor I.; Puhachenko, Kateryna S.

2013-01-01

The main principles of automated control systems construction with project organizational structures have been considered and the process flow sheet  for organizational systems control has been proposed. The architectural elements of the organizational system have been introduced and described. The instrumental tools of the graphodynamic systems theory have been used for the simulation modeling of hierarchical structures.

ASCI visualization tool evaluation, Version 2.0

Energy Technology Data Exchange (ETDEWEB)

Kegelmeyer, P. [ed.] [Sandia National Labs., Livermore, CA (United States). Center for Computational Engineering

1997-04-01

The charter of the ASCI Visualization Common Tools subgroup was to investigate and evaluate 3D scientific visualization tools. As part of that effort, a Tri-Lab evaluation effort was launched in February of 1996. The first step was to agree on a thoroughly documented list of 32 features against which all tool candidates would be evaluated. These evaluation criteria were both gleaned from a user survey and determined from informed extrapolation into the future, particularly as concerns the 3D nature and extremely large size of ASCI data sets. The second step was to winnow a field of 41 candidate tools down to 11. The selection principle was to be as inclusive as practical, retaining every tool that seemed to hold any promise of fulfilling all of ASCI`s visualization needs. These 11 tools were then closely investigated by volunteer evaluators distributed across LANL, LLNL, and SNL. This report contains the results of those evaluations, as well as a discussion of the evaluation philosophy and criteria.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

Science.gov (United States)

Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

2016-04-01

A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The application of lean principles in product development

DEFF Research Database (Denmark)

Bjarnø, Ole-Christian

2007-01-01

Although Lean Manufacturing has been a megatrend for several years, its principles have not been broadly applied in product development processes. We have therefore found it useful to look into the theories of lean manufacturing and to discuss how and to what extent they could be applied in the p......Although Lean Manufacturing has been a megatrend for several years, its principles have not been broadly applied in product development processes. We have therefore found it useful to look into the theories of lean manufacturing and to discuss how and to what extent they could be applied...... in the product development processes, and this study is compared with industrial practices in several front running companies in Denmark. From this research a suggestion for a framework and a tool-box for lean product development is created and discussed from a HR management, an implementation, an operational...

Mitochondrial protein acetylation mediates nutrient sensing of mitochondrial protein synthesis and mitonuclear protein balance.

Science.gov (United States)

Di Domenico, Antonella; Hofer, Annette; Tundo, Federica; Wenz, Tina

2014-11-01

Changes in nutrient supply require global metabolic reprogramming to optimize the utilization of the nutrients. Mitochondria as a central component of the cellular metabolism play a key role in this adaptive process. Since mitochondria harbor their own genome, which encodes essential enzymes, mitochondrial protein synthesis is a determinant of metabolic adaptation. While regulation of cytoplasmic protein synthesis in response to metabolic challenges has been studied in great detail, mechanisms which adapt mitochondrial translation in response to metabolic challenges remain elusive. Our results suggest that the mitochondrial acetylation status controlled by Sirt3 and its proposed opponent GCN5L1 is an important regulator of the metabolic adaptation of mitochondrial translation. Moreover, both proteins modulate regulators of cytoplasmic protein synthesis as well as the mitonuclear protein balance making Sirt3 and GCN5L1 key players in synchronizing mitochondrial and cytoplasmic translation. Our results thereby highlight regulation of mitochondrial translation as a novel component in the cellular nutrient sensing scheme and identify mitochondrial acetylation as a new regulatory principle for the metabolic competence of mitochondrial protein synthesis. © 2014 International Union of Biochemistry and Molecular Biology.

Protein kinase substrate identification on functional protein arrays

Directory of Open Access Journals (Sweden)

Zhou Fang

2008-02-01

Full Text Available Abstract Background Over the last decade, kinases have emerged as attractive therapeutic targets for a number of different diseases, and numerous high throughput screening efforts in the pharmaceutical community are directed towards discovery of compounds that regulate kinase function. The emerging utility of systems biology approaches has necessitated the development of multiplex tools suitable for proteomic-scale experiments to replace lower throughput technologies such as mass spectroscopy for the study of protein phosphorylation. Recently, a new approach for identifying substrates of protein kinases has applied the miniaturized format of functional protein arrays to characterize phosphorylation for thousands of candidate protein substrates in a single experiment. This method involves the addition of protein kinases in solution to arrays of immobilized proteins to identify substrates using highly sensitive radioactive detection and hit identification algorithms. Results To date, the factors required for optimal performance of protein array-based kinase substrate identification have not been described. In the current study, we have carried out a detailed characterization of the protein array-based method for kinase substrate identification, including an examination of the effects of time, buffer compositions, and protein concentration on the results. The protein array approach was compared to standard solution-based assays for assessing substrate phosphorylation, and a correlation of greater than 80% was observed. The results presented here demonstrate how novel substrates for protein kinases can be quickly identified from arrays containing thousands of human proteins to provide new clues to protein kinase function. In addition, a pooling-deconvolution strategy was developed and applied that enhances characterization of specific kinase-substrate relationships and decreases reagent consumption. Conclusion Functional protein microarrays are an

Mass spectrometric analysis of protein interactions

DEFF Research Database (Denmark)

Borch, Jonas; Jørgensen, Thomas J. D.; Roepstorff, Peter

2005-01-01

Mass spectrometry is a powerful tool for identification of interaction partners and structural characterization of protein interactions because of its high sensitivity, mass accuracy and tolerance towards sample heterogeneity. Several tools that allow studies of protein interaction are now...... available and recent developments that increase the confidence of studies of protein interaction by mass spectrometry include quantification of affinity-purified proteins by stable isotope labeling and reagents for surface topology studies that can be identified by mass-contributing reporters (e.g. isotope...... labels, cleavable cross-linkers or fragment ions. The use of mass spectrometers to study protein interactions using deuterium exchange and for analysis of intact protein complexes recently has progressed considerably....

Knoto-ID: a tool to study the entanglement of open protein chains using the concept of knotoids.

Science.gov (United States)

Dorier, Julien; Goundaroulis, Dimos; Benedetti, Fabrizio; Stasiak, Andrzej

2018-05-02

The backbone of most proteins forms an open curve. To study their entanglement, a common strategy consists in searching for the presence of knots in their backbones using topological invariants. However, this approach requires to close the curve into a loop, which alters the geometry of curve. Knoto-ID allows evaluating the entanglement of open curves without the need to close them, using the recent concept of knotoids which is a generalization of the classical knot theory to open curves. Knoto-ID can analyse the global topology of the full chain as well as the local topology by exhaustively studying all subchains or only determining the knotted core. Knoto-ID permits to localize topologically non-trivial protein folds that are not detected by informatics tools detecting knotted protein folds. Knoto-ID is written in C ++ and includes R (www.R-project.org) scripts to generate plots of projections maps, fingerprint matrices and disk matrices. Knoto-ID is distributed under the GNU General Public License (GPL), version 2 or any later version and is available at https://github.com/sib-swiss/Knoto-ID. A binary distribution for Mac OS X, Linux and Windows with detailed user guide and examples can be obtained from https://www.vital-it.ch/software/Knoto-ID. julien.dorier@sib.swiss.

High pressure as a tool for investigating protein-ligand interactions

International Nuclear Information System (INIS)

Marchal, S; Lange, R; Tortora, P; Balny, C

2004-01-01

In recent years, the application of pressure on biological systems has gained increasing interest. Pressure-induced destabilization of electrostatic and hydrophobic interactions is currently exploited to study conformational protein stability and macromolecular assemblies of proteins. Due to links between severe human pathologies and ordered protein oligomerization into aggregates, which have become apparent, a better knowledge of the molecular and structural determinants that ensure the packing efficiency and stability of such complexes has taken on special importance. Here, we report the effect of pressure on the property of human ataxin-3 of aggregation. The results indicate the importance of its polyglutamine chain length in the stability and the tendency of the protein to form spheroids. Partial unfolding of the protein leading to solvent exposure of hydrophobic domains appears to be a prerequisite in the aggregation process of ataxin-3

Experimental parameterization of an energy function for the simulation of unfolded proteins

DEFF Research Database (Denmark)

Norgaard, A.B.; Ferkinghoff-Borg, Jesper; Lindorff-Larsen, K.

2008-01-01

The determination of conformational preferences in unfolded and disordered proteins is an important challenge in structural biology. We here describe an algorithm to optimize energy functions for the simulation of unfolded proteins. The procedure is based on the maximum likelihood principle and e...... and can be applied to a range of experimental data and energy functions including the force fields used in molecular dynamics simulations.......The determination of conformational preferences in unfolded and disordered proteins is an important challenge in structural biology. We here describe an algorithm to optimize energy functions for the simulation of unfolded proteins. The procedure is based on the maximum likelihood principle...

Ion-Exchange Chromatography: Basic Principles and Application.

Science.gov (United States)

Cummins, Philip M; Rochfort, Keith D; O'Connor, Brendan F

2017-01-01

Ion-Exchange Chromatography (IEC) allows for the separation of ionizable molecules on the basis of differences in charge properties. Its large sample-handling capacity, broad applicability (particularly to proteins and enzymes), moderate cost, powerful resolving ability, and ease of scale-up and automation have led to it becoming one of the most versatile and widely used of all liquid chromatography (LC) techniques. In this chapter, we review the basic principles of IEC, as well as the broader criteria for selecting IEC conditions. By way of further illustration, we outline basic laboratory protocols to partially purify a soluble serine peptidase from bovine whole brain tissue, covering crude tissue extract preparation through to partial purification of the target enzyme using anion-exchange chromatography. Protocols for assaying total protein and enzyme activity in both pre- and post-IEC fractions are also described.

Manuscript title: antifungal proteins from moulds: analytical tools and potential application to dry-ripened foods.

Science.gov (United States)

Delgado, Josué; Owens, Rebecca A; Doyle, Sean; Asensio, Miguel A; Núñez, Félix

2016-08-01

Moulds growing on the surface of dry-ripened foods contribute to their sensory qualities, but some of them are able to produce mycotoxins that pose a hazard to consumers. Small cysteine-rich antifungal proteins (AFPs) from moulds are highly stable to pH and proteolysis and exhibit a broad inhibition spectrum against filamentous fungi, providing new chances to control hazardous moulds in fermented foods. The analytical tools for characterizing the cellular targets and affected pathways are reviewed. Strategies currently employed to study these mechanisms of action include 'omics' approaches that have come to the forefront in recent years, developing in tandem with genome sequencing of relevant organisms. These techniques contribute to a better understanding of the response of moulds against AFPs, allowing the design of complementary strategies to maximize or overcome the limitations of using AFPs on foods. AFPs alter chitin biosynthesis, and some fungi react inducing cell wall integrity (CWI) pathway. However, moulds able to increase chitin content at the cell wall by increasing proteins in either CWI or calmodulin-calcineurin signalling pathways will resist AFPs. Similarly, AFPs increase the intracellular levels of reactive oxygen species (ROS), and moulds increasing G-protein complex β subunit CpcB and/or enzymes to efficiently produce glutathione may evade apoptosis. Unknown aspects that need to be addressed include the interaction with mycotoxin production by less sensitive toxigenic moulds. However, significant steps have been taken to encourage the use of AFPs in intermediate-moisture foods, particularly for mould-ripened cheese and meat products.

Protein Engineering: Case Studies of Commercialized Engineered Products

Science.gov (United States)

Walsh, Gary

2007-01-01

Programs in biochemistry invariably encompass the principles of protein engineering. Students often display increased understanding and enthusiasm when theoretical concepts are underpinned by practical example. Herein are presented five case studies, each focusing upon a commercial protein product engineered to enhance its application-relevant…

Feynman’s clock, a new variational principle, and parallel-in-time quantum dynamics

Science.gov (United States)

McClean, Jarrod R.; Parkhill, John A.; Aspuru-Guzik, Alán

2013-01-01

We introduce a discrete-time variational principle inspired by the quantum clock originally proposed by Feynman and use it to write down quantum evolution as a ground-state eigenvalue problem. The construction allows one to apply ground-state quantum many-body theory to quantum dynamics, extending the reach of many highly developed tools from this fertile research area. Moreover, this formalism naturally leads to an algorithm to parallelize quantum simulation over time. We draw an explicit connection between previously known time-dependent variational principles and the time-embedded variational principle presented. Sample calculations are presented, applying the idea to a hydrogen molecule and the spin degrees of freedom of a model inorganic compound, demonstrating the parallel speedup of our method as well as its flexibility in applying ground-state methodologies. Finally, we take advantage of the unique perspective of this variational principle to examine the error of basis approximations in quantum dynamics. PMID:24062428

EDUCATION AND CULTURE (CONCERNING THE PROBLEM IN SEARCH THE PRINCIPLE OF EDUCATION ADEQUACY

Directory of Open Access Journals (Sweden)

Elena N. Yarkova

2015-01-01

Full Text Available This article develops a theme raised in the study «Education in Search of the Adequacy principle» by Yu. V. Larin, whereas the topical principle of modern education is the principle of cultural adequacy.The aim of the study is the analysis of value-semantic content of the principle of cultural adequacy of education. Methods of the study are formed by appeal to cultural approach connecting methods of ideal typing and value-semantic reconstruction.Results. In general, there are three types of culture based on the explication of the three modality human relations to the world: «the world is a condition», «the world is a tool», «the world is a purpose»; and, accordingly, three types of pedagogical culture: traditional, utilitarian, creative.Traditional pedagogical culture focuses on education homo traditional – traditional man, the individual, the obedient executor of the culture value semantic, regulatory policies and regulations, subordinating its activity transmitted from generation to generation tradition. The semantic space of traditional pedagogical culture principle of cultural adequacy education is defined as the principle of consistency with established tradition.Pedagogical culture of utilitarian type directs a homo utilitarian – utilitarian man, individuality, interpreting the culture value semantic, legal and regulatory requirements and on the basis of situational use, fully to the publication of his life publicly or individually beneficial activities. The utilitarian type principle of cultural adequacy of education is defined as the principle of consistency with the social and/or individual use in the semantic space of pedagogical culture.Pedagogical culture of creative types is aimed at nurturing homo creator – creative person whose existence is self-organization in the space between tradition and innovation, absolute and relative, universal and particular meanings of human existence, between social and individual

Dimensional cosmological principles

International Nuclear Information System (INIS)

Chi, L.K.

1985-01-01

The dimensional cosmological principles proposed by Wesson require that the density, pressure, and mass of cosmological models be functions of the dimensionless variables which are themselves combinations of the gravitational constant, the speed of light, and the spacetime coordinates. The space coordinate is not the comoving coordinate. In this paper, the dimensional cosmological principle and the dimensional perfect cosmological principle are reformulated by using the comoving coordinate. The dimensional perfect cosmological principle is further modified to allow the possibility that mass creation may occur. Self-similar spacetimes are found to be models obeying the new dimensional cosmological principle

Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.

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Gunnar Kleinau

Full Text Available In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR and different subtypes of G-proteins. The thyrotropin receptor (TSHR binds G-proteins promiscuously and activates both Gs (cAMP and Gq (IP. Our goal was to dissect selectivity patterns for both pathways in the intracellular region of this receptor. We were particularly interested in the participation of poorly investigated receptor parts.We systematically investigated the amino acids of intracellular loop (ICL 1 and helix 8 using site-directed mutagenesis alongside characterization of cAMP and IP accumulation. This approach was guided by a homology model of activated TSHR in complex with heterotrimeric Gq, using the X-ray structure of opsin with a bound G-protein peptide as a structural template.We provide evidence that ICL1 is significantly involved in G-protein activation and our model suggests potential interactions with subunits G alpha as well as G betagamma. Several amino acid substitutions impaired both IP and cAMP accumulation. Moreover, we found a few residues in ICL1 (L440, T441, H443 and helix 8 (R687 that are sensitive for Gq but not for Gs activation. Conversely, not even one residue was found that selectively affects cAMP accumulation only. Together with our previous mutagenesis data on ICL2 and ICL3 we provide here the first systematically completed map of potential interfaces between TSHR and heterotrimeric G-protein. The TSHR/Gq-heterotrimer complex is characterized by more selective interactions than the TSHR/Gs complex. In fact the receptor interface for binding Gs is a subset of that for Gq and we postulate that this may be true for other GPCRs coupling these G-proteins. Our findings support that G-protein coupling and preference is dominated by specific structural features at the intracellular region of the activated GPCR but is completed by additional complementary recognition patterns between receptor and G-protein

Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor.

Science.gov (United States)

Kleinau, Gunnar; Jaeschke, Holger; Worth, Catherine L; Mueller, Sandra; Gonzalez, Jorge; Paschke, Ralf; Krause, Gerd

2010-03-18

In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR) and different subtypes of G-proteins. The thyrotropin receptor (TSHR) binds G-proteins promiscuously and activates both Gs (cAMP) and Gq (IP). Our goal was to dissect selectivity patterns for both pathways in the intracellular region of this receptor. We were particularly interested in the participation of poorly investigated receptor parts.We systematically investigated the amino acids of intracellular loop (ICL) 1 and helix 8 using site-directed mutagenesis alongside characterization of cAMP and IP accumulation. This approach was guided by a homology model of activated TSHR in complex with heterotrimeric Gq, using the X-ray structure of opsin with a bound G-protein peptide as a structural template.We provide evidence that ICL1 is significantly involved in G-protein activation and our model suggests potential interactions with subunits G alpha as well as G betagamma. Several amino acid substitutions impaired both IP and cAMP accumulation. Moreover, we found a few residues in ICL1 (L440, T441, H443) and helix 8 (R687) that are sensitive for Gq but not for Gs activation. Conversely, not even one residue was found that selectively affects cAMP accumulation only. Together with our previous mutagenesis data on ICL2 and ICL3 we provide here the first systematically completed map of potential interfaces between TSHR and heterotrimeric G-protein. The TSHR/Gq-heterotrimer complex is characterized by more selective interactions than the TSHR/Gs complex. In fact the receptor interface for binding Gs is a subset of that for Gq and we postulate that this may be true for other GPCRs coupling these G-proteins. Our findings support that G-protein coupling and preference is dominated by specific structural features at the intracellular region of the activated GPCR but is completed by additional complementary recognition patterns between receptor and G-protein subtypes.

Protein engineering for metabolic engineering: current and next-generation tools

Science.gov (United States)

Marcheschi, Ryan J.; Gronenberg, Luisa S.; Liao, James C.

2014-01-01

Protein engineering in the context of metabolic engineering is increasingly important to the field of industrial biotechnology. As the demand for biologically-produced food, fuels, chemicals, food additives, and pharmaceuticals continues to grow, the ability to design and modify proteins to accomplish new functions will be required to meet the high productivity demands for the metabolism of engineered organisms. This article reviews advances of selecting, modeling, and engineering proteins to improve or alter their activity. Some of the methods have only recently been developed for general use and are just beginning to find greater application in the metabolic engineering community. We also discuss methods of generating random and targeted diversity in proteins to generate mutant libraries for analysis. Recent uses of these techniques to alter cofactor use, produce non-natural amino acids, alcohols, and carboxylic acids, and alter organism phenotypes are presented and discussed as examples of the successful engineering of proteins for metabolic engineering purposes. PMID:23589443

The algorithms and principles of non-photorealistic graphics

CERN Document Server

Geng, Weidong

2011-01-01

""The Algorithms and Principles of Non-photorealistic Graphics: Artistic Rendering and Cartoon Animation"" provides a conceptual framework for and comprehensive and up-to-date coverage of research on non-photorealistic computer graphics including methodologies, algorithms and software tools dedicated to generating artistic and meaningful images and animations. This book mainly discusses how to create art from a blank canvas, how to convert the source images into pictures with the desired visual effects, how to generate artistic renditions from 3D models, how to synthesize expressive pictures f

Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling

Science.gov (United States)

Shin, Young Shik; Remacle, F.; Fan, Rong; Hwang, Kiwook; Wei, Wei; Ahmad, Habib; Levine, R.D.; Heath, James R.

2011-01-01

Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network. PMID:21575571

Principles of health information systems in developing countries.

Science.gov (United States)

Krickeberg, Klaus

The setting of this article is an all-embracing Health Information System (HIS)* of the type that exists mainly in developing and transition countries. It was inspired by work in Vietnam and other places. The article discusses the basic principles on which a well-functioning HIS needs to rest regardless of the technical means employed (paper, electronic devices). Eleven principles for designing or reforming a HIS are identified, including: explicit description of the underlying units (target population) and variables; no list of indicators to be fixed in advance; only one register per target population; technical coordination between registers and reports; correction algorithms; local use of data and indicators; autonomy of health institutions regarding the information that concerns them; and novel use of registers for various studies. Apart from their technical role, these principles give shape to the philosophy that underlies this article, and make clear that a HIS is not only a tool for collecting indicators; it is intimately tied to clinical and preventive practice, as well as to health management and health economy. In fact, it permeates the entire health system. It can potentially play a much more extended, varied, and useful role than simply that of providing health services to a community.

Principles of effective USA federal fire management plans

Science.gov (United States)

Meyer, Marc D.; Roberts, Susan L.; Wills, Robin; Brooks, Matthew L.; Winford, Eric M.

2015-01-01

Federal fire management plans are essential implementation guides for the management of wildland fire on federal lands. Recent changes in federal fire policy implementation guidance and fire science information suggest the need for substantial changes in federal fire management plans of the United States. Federal land management agencies are also undergoing land management planning efforts that will initiate revision of fire management plans across the country. Using the southern Sierra Nevada as a case study, we briefly describe the underlying framework of fire management plans, assess their consistency with guiding principles based on current science information and federal policy guidance, and provide recommendations for the development of future fire management plans. Based on our review, we recommend that future fire management plans be: (1) consistent and compatible, (2) collaborative, (3) clear and comprehensive, (4) spatially and temporally scalable, (5) informed by the best available science, and (6) flexible and adaptive. In addition, we identify and describe several strategic guides or “tools” that can enhance these core principles and benefit future fire management plans in the following areas: planning and prioritization, science integration, climate change adaptation, partnerships, monitoring, education and communication, and applied fire management. These principles and tools are essential to successfully realize fire management goals and objectives in a rapidly changing world.

Ancestral mutations as a tool for solubilizing proteins: The case of a hydrophobic phosphate-binding protein

Directory of Open Access Journals (Sweden)

Daniel Gonzalez

2014-01-01

Full Text Available Stable and soluble proteins are ideal candidates for functional and structural studies. Unfortunately, some proteins or enzymes can be difficult to isolate, being sometimes poorly expressed in heterologous systems, insoluble and/or unstable. Numerous methods have been developed to address these issues, from the screening of various expression systems to the modification of the target protein itself. Here we use a hydrophobic, aggregation-prone, phosphate-binding protein (HPBP as a case study. We describe a simple and fast method that selectively uses ancestral mutations to generate a soluble, stable and functional variant of the target protein, here named sHPBP. This variant is highly expressed in Escherichia coli, is easily purified and its structure was solved at much higher resolution than its wild-type progenitor (1.3 versus 1.9 Å, respectively.

ESIprot: a universal tool for charge state determination and molecular weight calculation of proteins from electrospray ionization mass spectrometry data.

Science.gov (United States)

Winkler, Robert

2010-02-01

Electrospray ionization (ESI) ion trap mass spectrometers with relatively low resolution are frequently used for the analysis of natural products and peptides. Although ESI spectra of multiply charged protein molecules also can be measured on this type of devices, only average spectra are produced for the majority of naturally occurring proteins. Evaluating such ESI protein spectra would provide valuable information about the native state of investigated proteins. However, no suitable and freely available software could be found which allows the charge state determination and molecular weight calculation of single proteins from average ESI-MS data. Therefore, an algorithm based on standard deviation optimization (scatter minimization) was implemented for the analysis of protein ESI-MS data. The resulting software ESIprot was tested with ESI-MS data of six intact reference proteins between 12.4 and 66.7 kDa. In all cases, the correct charge states could be determined. The obtained absolute mass errors were in a range between -0.2 and 1.2 Da, the relative errors below 30 ppm. The possible mass accuracy allows for valid conclusions about the actual condition of proteins. Moreover, the ESIprot algorithm demonstrates an extraordinary robustness and allows spectral interpretation from as little as two peaks, given sufficient quality of the provided m/z data, without the necessity for peak intensity data. ESIprot is independent from the raw data format and the computer platform, making it a versatile tool for mass spectrometrists. The program code was released under the open-source GPLv3 license to support future developments of mass spectrometry software. Copyright 2010 John Wiley & Sons, Ltd.

Co-doping as a tool for tuning the optical properties of singlewalled carbon nanotubes: A first principles study

Science.gov (United States)

Sharma, Deepa; Jaggi, Neena

2017-07-01

This paper presents a first principles study on the effect of co-doping on various optical spectra of a zigzag single-walled carbon nanotube (SWCNT). Optical spectra of a pristine SWCNT, SWCNT co-doped with Aluminum (Al) & Phosphorus (P) and another one co-doped with Al, P and Nitrogen (N) have been calculated using density functional theory (DFT).The theory has been implemented using the Cambridge sequential total energy package (CASTEP) code available as a userfriendly module with the software 'Material Studio'. Polarized and unpolarized light as well as light through polycrystalline media have been considered. The dependence of various spectra on the status of incident light presents a clear evidence of anisotropicity in the optical properties. Analysis of the simulated spectra involves calculation and comparison of different optical properties like dielectric function, reflectivity, refractive index, conductivity and loss function for the pristine and co-doped SWCNTs. Noticeable variations are observed in the optical properties on simultaneously doping the SWCNT with Al and P and then further introducing N atom into the structure so that it can be concluded that co-doping (simultaneous doping with different combinations of dopants) can be evolved as a novel and effective tool for tailoring the optical properties of SWCNTs as per the requirements while designing an optical device. It will prove to be highly significant for effective designing of SWCNT based sensitive optical devices for a variety of technological applications.

Analysis of Protein Phosphorylation and Its Functional Impact on Protein-Protein Interactions via Text Mining of the Scientific Literature.

Science.gov (United States)

Wang, Qinghua; Ross, Karen E; Huang, Hongzhan; Ren, Jia; Li, Gang; Vijay-Shanker, K; Wu, Cathy H; Arighi, Cecilia N

2017-01-01

Post-translational modifications (PTMs) are one of the main contributors to the diversity of proteoforms in the proteomic landscape. In particular, protein phosphorylation represents an essential regulatory mechanism that plays a role in many biological processes. Protein kinases, the enzymes catalyzing this reaction, are key participants in metabolic and signaling pathways. Their activation or inactivation dictate downstream events: what substrates are modified and their subsequent impact (e.g., activation state, localization, protein-protein interactions (PPIs)). The biomedical literature continues to be the main source of evidence for experimental information about protein phosphorylation. Automatic methods to bring together phosphorylation events and phosphorylation-dependent PPIs can help to summarize the current knowledge and to expose hidden connections. In this chapter, we demonstrate two text mining tools, RLIMS-P and eFIP, for the retrieval and extraction of kinase-substrate-site data and phosphorylation-dependent PPIs from the literature. These tools offer several advantages over a literature search in PubMed as their results are specific for phosphorylation. RLIMS-P and eFIP results can be sorted, organized, and viewed in multiple ways to answer relevant biological questions, and the protein mentions are linked to UniProt identifiers.

Implementation of utaut model to understand the use of virtual classroom principle in higher education

Science.gov (United States)

Aditya, B. R.; Permadi, A.

2018-03-01

This paper describes implementation of Unified Theory of Acceptance and User of Technology (UTAUT) model to assess the use of virtual classroom in support of teaching and learning in higher education. The purpose of this research is how virtual classroom that has fulfilled the basic principle can be accepted and used by students positively. This research methodology uses the quantitative and descriptive approach with a questionnaire as a tool for measuring the height of virtual classroom principle acception. This research uses a sample of 105 students in D3 Informatics Management at Telkom University. The result of this research is that the use of classroom virtual principle are positive and relevant to the students in higher education.

Gene regulatory networks in lactation: identification of global principles using bioinformatics

Directory of Open Access Journals (Sweden)

Pollard Katherine S

2007-11-01

Full Text Available Abstract Background The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood. Results Mammary gland microarray data, cellular localization data, protein-protein interactions, and literature-mined genes were integrated and analyzed using statistics, principal component analysis, gene ontology analysis, pathway analysis, and network analysis to identify global biological principles that govern molecular events during pregnancy, lactation, and involution. Conclusion Several key principles were derived: (1 nearly a third of the transcriptome fluctuates to build, run, and disassemble the lactation apparatus; (2 genes encoding the secretory machinery are transcribed prior to lactation; (3 the diversity of the endogenous portion of the milk proteome is derived from fewer than 100 transcripts; (4 while some genes are differentially transcribed near the onset of lactation, the lactation switch is primarily post-transcriptionally mediated; (5 the secretion of materials during lactation occurs not by up-regulation of novel genomic functions, but by widespread transcriptional suppression of functions such as protein degradation and cell-environment communication; (6 the involution switch is primarily transcriptionally mediated; and (7 during early involution, the transcriptional state is partially reverted to the pre-lactation state. A new hypothesis for secretory diminution is suggested – milk production gradually declines because the secretory machinery is not transcriptionally replenished. A comprehensive network of protein interactions during lactation is assembled and new regulatory gene targets are identified. Less than one fifth of the transcriptionally regulated nodes in this lactation network have been previously explored in the context of lactation. Implications for future research in mammary and cancer biology are discussed.

A New Principle in Physics: the Principle 'Finiteness', and Some Consequences

International Nuclear Information System (INIS)

Sternlieb, Abraham

2010-01-01

In this paper I propose a new principle in physics: the principle of 'finiteness'. It stems from the definition of physics as a science that deals (among other things) with measurable dimensional physical quantities. Since measurement results, including their errors, are always finite, the principle of finiteness postulates that the mathematical formulation of 'legitimate' laws of physics should prevent exactly zero or infinite solutions. Some consequences of the principle of finiteness are discussed, in general, and then more specifically in the fields of special relativity, quantum mechanics, and quantum gravity. The consequences are derived independently of any other theory or principle in physics. I propose 'finiteness' as a postulate (like the constancy of the speed of light in vacuum, 'c'), as opposed to a notion whose validity has to be corroborated by, or derived theoretically or experimentally from other facts, theories, or principles.

Sequence-specific capture of protein-DNA complexes for mass spectrometric protein identification.

Directory of Open Access Journals (Sweden)

Cheng-Hsien Wu

Full Text Available The regulation of gene transcription is fundamental to the existence of complex multicellular organisms such as humans. Although it is widely recognized that much of gene regulation is controlled by gene-specific protein-DNA interactions, there presently exists little in the way of tools to identify proteins that interact with the genome at locations of interest. We have developed a novel strategy to address this problem, which we refer to as GENECAPP, for Global ExoNuclease-based Enrichment of Chromatin-Associated Proteins for Proteomics. In this approach, formaldehyde cross-linking is employed to covalently link DNA to its associated proteins; subsequent fragmentation of the DNA, followed by exonuclease digestion, produces a single-stranded region of the DNA that enables sequence-specific hybridization capture of the protein-DNA complex on a solid support. Mass spectrometric (MS analysis of the captured proteins is then used for their identification and/or quantification. We show here the development and optimization of GENECAPP for an in vitro model system, comprised of the murine insulin-like growth factor-binding protein 1 (IGFBP1 promoter region and FoxO1, a member of the forkhead rhabdomyosarcoma (FoxO subfamily of transcription factors, which binds specifically to the IGFBP1 promoter. This novel strategy provides a powerful tool for studies of protein-DNA and protein-protein interactions.

Fundamental principles in bacterial physiology—history, recent progress, and the future with focus on cell size control: a review

Science.gov (United States)

Jun, Suckjoon; Si, Fangwei; Pugatch, Rami; Scott, Matthew

2018-05-01

Bacterial physiology is a branch of biology that aims to understand overarching principles of cellular reproduction. Many important issues in bacterial physiology are inherently quantitative, and major contributors to the field have often brought together tools and ways of thinking from multiple disciplines. This article presents a comprehensive overview of major ideas and approaches developed since the early 20th century for anyone who is interested in the fundamental problems in bacterial physiology. This article is divided into two parts. In the first part (sections 1–3), we review the first ‘golden era’ of bacterial physiology from the 1940s to early 1970s and provide a complete list of major references from that period. In the second part (sections 4–7), we explain how the pioneering work from the first golden era has influenced various rediscoveries of general quantitative principles and significant further development in modern bacterial physiology. Specifically, section 4 presents the history and current progress of the ‘adder’ principle of cell size homeostasis. Section 5 discusses the implications of coarse-graining the cellular protein composition, and how the coarse-grained proteome ‘sectors’ re-balance under different growth conditions. Section 6 focuses on physiological invariants, and explains how they are the key to understanding the coordination between growth and the cell cycle underlying cell size control in steady-state growth. Section 7 overviews how the temporal organization of all the internal processes enables balanced growth. In the final section 8, we conclude by discussing the remaining challenges for the future in the field.

The CANDU alarm analysis tool (CAAT)

Energy Technology Data Exchange (ETDEWEB)

Davey, E C; Feher, M P; Lupton, L R [Control Centre Technology Branch, ON (Canada)

1997-09-01

AECL undertook the development of a software tool to assist alarm system designers and maintainers based on feedback from several utilities and design groups. The software application is called the CANDU Alarm Analysis Tool (CAAT) and is being developed to: Reduce by one half the effort required to initially implement and commission alarm system improvements; improve the operational relevance, consistency and accuracy of station alarm information; record the basis for alarm-related decisions; provide printed reports of the current alarm configuration; and, make day-to-day maintenance of the alarm database less tedious and more cost-effective. The CAAT assists users in accessing, sorting and recording relevant information, design rules, decisions, and provides reports in support of alarm system maintenance, analysis of design changes, or regulatory inquiry. The paper discusses the need for such a tool, outlines the application objectives and principles used to guide tool development, describes the how specific tool features support user design and maintenance tasks, and relates the lessons learned from early application experience. (author). 4 refs, 2 figs.

The CANDU alarm analysis tool (CAAT)

International Nuclear Information System (INIS)

Davey, E.C.; Feher, M.P.; Lupton, L.R.

1997-01-01

AECL undertook the development of a software tool to assist alarm system designers and maintainers based on feedback from several utilities and design groups. The software application is called the CANDU Alarm Analysis Tool (CAAT) and is being developed to: Reduce by one half the effort required to initially implement and commission alarm system improvements; improve the operational relevance, consistency and accuracy of station alarm information; record the basis for alarm-related decisions; provide printed reports of the current alarm configuration; and, make day-to-day maintenance of the alarm database less tedious and more cost-effective. The CAAT assists users in accessing, sorting and recording relevant information, design rules, decisions, and provides reports in support of alarm system maintenance, analysis of design changes, or regulatory inquiry. The paper discusses the need for such a tool, outlines the application objectives and principles used to guide tool development, describes the how specific tool features support user design and maintenance tasks, and relates the lessons learned from early application experience. (author). 4 refs, 2 figs

Equivalence principles and electromagnetism

Science.gov (United States)

Ni, W.-T.

1977-01-01

The implications of the weak equivalence principles are investigated in detail for electromagnetic systems in a general framework. In particular, it is shown that the universality of free-fall trajectories (Galileo weak equivalence principle) does not imply the validity of the Einstein equivalence principle. However, the Galileo principle plus the universality of free-fall rotation states does imply the Einstein principle.

Quantum Action Principle with Generalized Uncertainty Principle

OpenAIRE

Gu, Jie

2013-01-01

One of the common features in all promising candidates of quantum gravity is the existence of a minimal length scale, which naturally emerges with a generalized uncertainty principle, or equivalently a modified commutation relation. Schwinger's quantum action principle was modified to incorporate this modification, and was applied to the calculation of the kernel of a free particle, partly recovering the result previously studied using path integral.

TALE-PvuII fusion proteins--novel tools for gene targeting.

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

VP22 herpes simplex virus protein can transduce proteins into stem cells

Energy Technology Data Exchange (ETDEWEB)

Gabanyi, I.; Lojudice, F.H.; Kossugue, P.M. [Centro de Terapia Celular e Molecular, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Rebelato, E. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Demasi, M.A.; Sogayar, M.C. [Centro de Terapia Celular e Molecular, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil)

2013-02-01

The type I herpes simplex virus VP22 tegument protein is abundant and well known for its ability to translocate proteins from one cell to the other. In spite of some reports questioning its ability to translocate proteins by attributing the results observed to fixation artifacts or simple attachment to the cell membrane, VP22 has been used to deliver several proteins into different cell types, triggering the expected cell response. However, the question of the ability of VP22 to enter stem cells has not been addressed. We investigated whether VP22 could be used as a tool to be applied in stem cell research and differentiation due to its capacity to internalize other proteins without altering the cell genome. We generated a VP22.eGFP construct to evaluate whether VP22 could be internalized and carry another protein with it into two different types of stem cells, namely adult human dental pulp stem cells and mouse embryonic stem cells. We generated a VP22.eGFP fusion protein and demonstrated that, in fact, it enters stem cells. Therefore, this system may be used as a tool to deliver various proteins into stem cells, allowing stem cell research, differentiation and the generation of induced pluripotent stem cells in the absence of genome alterations.

VP22 herpes simplex virus protein can transduce proteins into stem cells

International Nuclear Information System (INIS)

Gabanyi, I.; Lojudice, F.H.; Kossugue, P.M.; Rebelato, E.; Demasi, M.A.; Sogayar, M.C.

2013-01-01

The type I herpes simplex virus VP22 tegument protein is abundant and well known for its ability to translocate proteins from one cell to the other. In spite of some reports questioning its ability to translocate proteins by attributing the results observed to fixation artifacts or simple attachment to the cell membrane, VP22 has been used to deliver several proteins into different cell types, triggering the expected cell response. However, the question of the ability of VP22 to enter stem cells has not been addressed. We investigated whether VP22 could be used as a tool to be applied in stem cell research and differentiation due to its capacity to internalize other proteins without altering the cell genome. We generated a VP22.eGFP construct to evaluate whether VP22 could be internalized and carry another protein with it into two different types of stem cells, namely adult human dental pulp stem cells and mouse embryonic stem cells. We generated a VP22.eGFP fusion protein and demonstrated that, in fact, it enters stem cells. Therefore, this system may be used as a tool to deliver various proteins into stem cells, allowing stem cell research, differentiation and the generation of induced pluripotent stem cells in the absence of genome alterations

Computational Studies of pH Sensing Design Principles in Proteins

Science.gov (United States)

Garrido Ruiz, Diego

Changes in pH are important regulatory signals for biological function, under physiological and pathological conditions. Recent advances in computer simulations strategies have made the exploration of the effects of charge titrations on protein function possible. In this work, I make use of these strategies to investigate the thermodynamic coupling between conformation and protonation states that give rise to pH-dependent function. As motivation for the rest of the work, I start by presenting a collaborative investigation on a pH-sensing mutant of the EGFR tyrosine kinase common to a set of distinct cancers. From then, I reduce the complexity of the systems under study to build models where exact enumeration of states is possible to inquire about the nature of the couplings between protonation states and conformation. Finally, I discuss detailed simulations of pH-sensing proteins for which I use the expectations and insights generated with simple models to identify and interpret couplings of interest for pH-dependent behavior.

ErgoTMC, A New Tool For Human-Centered TMC Design

Science.gov (United States)

2000-04-01

The Federal Highway Administration (FHWA) has recently made available a new tool to assist Transportation Management Center (TMC) managers and designers in incorporating human-centered design principles into their TMCs. ErgoTMC, a web site tailored t...

Seed Storage Proteins as a System for Teaching Protein Identification by Mass Spectrometry in Biochemistry Laboratory

Science.gov (United States)

Wilson, Karl A.; Tan-Wilson, Anna

2013-01-01

Mass spectrometry (MS) has become an important tool in studying biological systems. One application is the identification of proteins and peptides by the matching of peptide and peptide fragment masses to the sequences of proteins in protein sequence databases. Often prior protein separation of complex protein mixtures by 2D-PAGE is needed,…

A linear maglev guide for machine tools

Energy Technology Data Exchange (ETDEWEB)

Tieste, K D [Inst. of Mechanics, Univ. of Hannover (Germany); Popp, K [Inst. of Mechanics, Univ. of Hannover (Germany)

1996-12-31

Machine tools require linear guides with high slide velocity and very high position accuracy. The three tasks of a linear guide - supporting, guiding and driving - shall be realised by means of active magnetic bearings (AMB). The resulting linear magnetically levitated (maglev) guide has to accomplish the following characteristics: High stiffness, good damping and low noise as well as low heat production. First research on a one degree-of-freedom (DOF) support magnet unit aimed at the development of components and efficient control strategies for the linear maglev guide. The actual research is directed to realise a five DOF linear maglev guide for machine tools without drive to answer the question whether the maglev principle can be used for a linear axis in a machine tool. (orig.)

Physics of protein folding

Science.gov (United States)

Finkelstein, A. V.; Galzitskaya, O. V.

2004-04-01

Protein physics is grounded on three fundamental experimental facts: protein, this long heteropolymer, has a well defined compact three-dimensional structure; this structure can spontaneously arise from the unfolded protein chain in appropriate environment; and this structure is separated from the unfolded state of the chain by the “all-or-none” phase transition, which ensures robustness of protein structure and therefore of its action. The aim of this review is to consider modern understanding of physical principles of self-organization of protein structures and to overview such important features of this process, as finding out the unique protein structure among zillions alternatives, nucleation of the folding process and metastable folding intermediates. Towards this end we will consider the main experimental facts and simple, mostly phenomenological theoretical models. We will concentrate on relatively small (single-domain) water-soluble globular proteins (whose structure and especially folding are much better studied and understood than those of large or membrane and fibrous proteins) and consider kinetic and structural aspects of transition of initially unfolded protein chains into their final solid (“native”) 3D structures.

Designing proteins for therapeutic applications.

Science.gov (United States)

Lazar, Greg A; Marshall, Shannon A; Plecs, Joseph J; Mayo, Stephen L; Desjarlais, John R

2003-08-01

Protein design is becoming an increasingly useful tool for optimizing protein drugs and creating novel biotherapeutics. Recent progress includes the engineering of monoclonal antibodies, cytokines, enzymes and viral fusion inhibitors.

Application of a 16-bit microprocessor to the digital control of machine tools

International Nuclear Information System (INIS)

Issaly, Alain

1979-01-01

After an overview of machine tools (various types, definition standardization, associated technologies for motors and position sensors), this research thesis describes the principles of computer-based digital control: classification of machine tool command systems, machining programming, programming languages, dialog function, interpolation function, servo-control function, tool compensation function. The author reports the application of a 16-bit microprocessor to the computer-based digital control of a machine tool: feasibility, selection of microprocessor, hardware presentation, software development and description, machining mode, translation-loading mode

Noncommutative Common Cause Principles in algebraic quantum field theory

International Nuclear Information System (INIS)

Hofer-Szabó, Gábor; Vecsernyés, Péter

2013-01-01

States in algebraic quantum field theory “typically” establish correlation between spacelike separated events. Reichenbach's Common Cause Principle, generalized to the quantum field theoretical setting, offers an apt tool to causally account for these superluminal correlations. In the paper we motivate first why commutativity between the common cause and the correlating events should be abandoned in the definition of the common cause. Then we show that the Noncommutative Weak Common Cause Principle holds in algebraic quantum field theory with locally finite degrees of freedom. Namely, for any pair of projections A, B supported in spacelike separated regions V A and V B , respectively, there is a local projection C not necessarily commuting with A and B such that C is supported within the union of the backward light cones of V A and V B and the set {C, C ⊥ } screens off the correlation between A and B.

Evolutionary multimodal optimization using the principle of locality

KAUST Repository

Wong, Kachun; Wu, Chunho; Mok, Ricky; Peng, Chengbin; Zhang, Zhaolei

2012-01-01

The principle of locality is one of the most widely used concepts in designing computing systems. To explore the principle in evolutionary computation, crowding differential evolution is incorporated with locality for multimodal optimization. Instead of generating trial vectors randomly, the first method proposed takes advantage of spatial locality to generate trial vectors. Temporal locality is also adopted to help generate offspring in the second method proposed. Temporal and spatial locality are then applied together in the third method proposed. Numerical experiments are conducted to compare the proposed methods with the state-of-the-art methods on benchmark functions. Experimental analysis is undertaken to observe the effect of locality and the synergy between temporal locality and spatial locality. Further experiments are also conducted on two application problems. One is the varied-line-spacing holographic grating design problem, while the other is the protein structure prediction problem. The numerical results demonstrate the effectiveness of the methods proposed. © 2012 Elsevier Inc. All rights reserved.

Evolutionary multimodal optimization using the principle of locality

KAUST Repository

Wong, Kachun

2012-07-01

The principle of locality is one of the most widely used concepts in designing computing systems. To explore the principle in evolutionary computation, crowding differential evolution is incorporated with locality for multimodal optimization. Instead of generating trial vectors randomly, the first method proposed takes advantage of spatial locality to generate trial vectors. Temporal locality is also adopted to help generate offspring in the second method proposed. Temporal and spatial locality are then applied together in the third method proposed. Numerical experiments are conducted to compare the proposed methods with the state-of-the-art methods on benchmark functions. Experimental analysis is undertaken to observe the effect of locality and the synergy between temporal locality and spatial locality. Further experiments are also conducted on two application problems. One is the varied-line-spacing holographic grating design problem, while the other is the protein structure prediction problem. The numerical results demonstrate the effectiveness of the methods proposed. © 2012 Elsevier Inc. All rights reserved.

Chemical protein synthesis: Inventing synthetic methods to decipher how proteins work.

Science.gov (United States)

Kent, Stephen

2017-09-15

Total chemical synthesis of proteins has been rendered practical by the chemical ligation principle: chemoselective condensation of unprotected peptide segments equipped with unique, mutually reactive functional groups, enabled by formation of a non-native replacement for the peptide bond. Ligation chemistries are briefly described, including native chemical ligation - thioester-mediated, amide-forming reaction at Xaa-Cys sites - and its extensions. Case studies from the author's own works are used to illustrate the utility and applications of chemical protein synthesis. Selected recent developments in the field are briefly discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

A review of the thermodynamics of protein association to ligands, protein adsorption, and adsorption isotherms

DEFF Research Database (Denmark)

Mollerup, Jørgen

2008-01-01

The application of thermodynamic models in the development of chromatographic separation processes is discussed. The paper analyses the thermodynamic principles of protein adsorption. It can be modeled either as a reversible association between the adsorbate and the ligands or as a steady...

Protein folding simulations: from coarse-grained model to all-atom model.

Science.gov (United States)

Zhang, Jian; Li, Wenfei; Wang, Jun; Qin, Meng; Wu, Lei; Yan, Zhiqiang; Xu, Weixin; Zuo, Guanghong; Wang, Wei

2009-06-01

Protein folding is an important and challenging problem in molecular biology. During the last two decades, molecular dynamics (MD) simulation has proved to be a paramount tool and was widely used to study protein structures, folding kinetics and thermodynamics, and structure-stability-function relationship. It was also used to help engineering and designing new proteins, and to answer even more general questions such as the minimal number of amino acid or the evolution principle of protein families. Nowadays, the MD simulation is still undergoing rapid developments. The first trend is to toward developing new coarse-grained models and studying larger and more complex molecular systems such as protein-protein complex and their assembling process, amyloid related aggregations, and structure and motion of chaperons, motors, channels and virus capsides; the second trend is toward building high resolution models and explore more detailed and accurate pictures of protein folding and the associated processes, such as the coordination bond or disulfide bond involved folding, the polarization, charge transfer and protonate/deprotonate process involved in metal coupled folding, and the ion permeation and its coupling with the kinetics of channels. On these new territories, MD simulations have given many promising results and will continue to offer exciting views. Here, we review several new subjects investigated by using MD simulations as well as the corresponding developments of appropriate protein models. These include but are not limited to the attempt to go beyond the topology based Gō-like model and characterize the energetic factors in protein structures and dynamics, the study of the thermodynamics and kinetics of disulfide bond involved protein folding, the modeling of the interactions between chaperonin and the encapsulated protein and the protein folding under this circumstance, the effort to clarify the important yet still elusive folding mechanism of protein BBL

PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system

Directory of Open Access Journals (Sweden)

Picard-Cloutier Aude

2007-12-01

Full Text Available Abstract Background In the "post-genome" era, mass spectrometry (MS has become an important method for the analysis of proteins and the rapid advancement of this technique, in combination with other proteomics methods, results in an increasing amount of proteome data. This data must be archived and analysed using specialized bioinformatics tools. Description We herein describe "PARPs database," a data analysis and management pipeline for liquid chromatography tandem mass spectrometry (LC-MS/MS proteomics. PARPs database is a web-based tool whose features include experiment annotation, protein database searching, protein sequence management, as well as data-mining of the peptides and proteins identified. Conclusion Using this pipeline, we have successfully identified several interactions of biological significance between PARP-1 and other proteins, namely RFC-1, 2, 3, 4 and 5.

Thermodynamic modeling of the Ca-Sn system based on finite temperature quantities from first-principles and experiment

International Nuclear Information System (INIS)

Ohno, M.; Kozlov, A.; Arroyave, R.; Liu, Z.K.; Schmid-Fetzer, R.

2006-01-01

The thermodynamic model of the Ca-Sn system was obtained, utilizing the first-principles total energies and heat capacities calculated from 0 K to the melting points of the major phases. Since the first-principles result for the formation energy of the dominating Ca 2 Sn intermetallic phase is drastically different from the reported experimental data, we performed two types of thermodynamic modeling: one based on the first-principles output and the other based on the experimental data. In the former modeling, the Gibbs energies of the intermetallic compounds were fully quantified from the first-principles finite temperature properties and the superiority of the former thermodynamic description is demonstrated. It is shown that it is the combination of finite temperature first-principle calculations and the Calphad modeling tool that provides a sound basis for identifying and deciding on conflicting key thermodynamic data in the Ca-Sn system

Patient-Centered Tools for Medication Information Search.

Science.gov (United States)

Wilcox, Lauren; Feiner, Steven; Elhadad, Noémie; Vawdrey, David; Tran, Tran H

2014-05-20

Recent research focused on online health information seeking highlights a heavy reliance on general-purpose search engines. However, current general-purpose search interfaces do not necessarily provide adequate support for non-experts in identifying suitable sources of health information. Popular search engines have recently introduced search tools in their user interfaces for a range of topics. In this work, we explore how such tools can support non-expert, patient-centered health information search. Scoping the current work to medication-related search, we report on findings from a formative study focused on the design of patient-centered, medication-information search tools. Our study included qualitative interviews with patients, family members, and domain experts, as well as observations of their use of Remedy, a technology probe embodying a set of search tools. Post-operative cardiothoracic surgery patients and their visiting family members used the tools to find information about their hospital medications and were interviewed before and after their use. Domain experts conducted similar search tasks and provided qualitative feedback on their preferences and recommendations for designing these tools. Findings from our study suggest the importance of four valuation principles underlying our tools: credibility, readability, consumer perspective, and topical relevance.

Competitive protein binding assay

International Nuclear Information System (INIS)

Kaneko, Toshio; Oka, Hiroshi

1975-01-01

The measurement of cyclic GMP (cGMP) by competitive protein binding assay was described and discussed. The principle of binding assay was represented briefly. Procedures of our method by binding protein consisted of preparation of cGMP binding protein, selection of 3 H-cyclic GMP on market, and measurement procedures. In our method, binding protein was isolated from the chrysalis of silk worm. This method was discussed from the points of incubation medium, specificity of binding protein, the separation of bound cGMP from free cGMP, and treatment of tissue from which cGMP was extracted. cGMP existing in the tissue was only one tenth or one scores of cGMP, and in addition, cGMP competed with cGMP in binding with binding protein. Therefore, Murad's technique was applied to the isolation of cGMP. This method provided the measurement with sufficient accuracy; the contamination by cAMP was within several per cent. (Kanao, N.)

APPLYING THE PRINCIPLES OF ACCOUNTING IN

OpenAIRE

NAGY CRISTINA MIHAELA; SABĂU CRĂCIUN; ”Tibiscus” University of Timişoara, Faculty of Economic Science

2015-01-01

The application of accounting principles (accounting principle on accrual basis; principle of business continuity; method consistency principle; prudence principle; independence principle; the principle of separate valuation of assets and liabilities; intangibility principle; non-compensation principle; the principle of substance over form; the principle of threshold significance) to companies that are in bankruptcy procedure has a number of particularities. Thus, some principl...

Protein engineering and its applications in food industry.

Science.gov (United States)

Kapoor, Swati; Rafiq, Aasima; Sharma, Savita

2017-07-24

Protein engineering is a young discipline that has been branched out from the field of genetic engineering. Protein engineering is based on the available knowledge about the proteins structure/function(s), tools/instruments, software, bioinformatics database, available cloned gene, knowledge about available protein, vectors, recombinant strains and other materials that could lead to change in the protein backbone. Protein produced properly from genetic engineering process means a protein that is able to fold correctly and to do particular function(s) efficiently even after being subjected to engineering practices. Protein is modified through its gene or chemically. However, modification of protein through gene is easier. There is no specific limitation of Protein Engineering tools; any technique that can lead to change the protein constituent of amino acid and result in the modification of protein structure/function is in the frame of Protein Engineering. Meanwhile, there are some common tools used to reach a specific target. More active industrial and pharmaceutical based proteins have been invented by the field of Protein Engineering to introduce new function as well as to change its interaction with surrounding environment. A variety of protein engineering applications have been reported in the literature. These applications range from biocatalysis for food and industry to environmental, medical and nanobiotechnology applications. Successful combinations of various protein engineering methods had led to successful results in food industries and have created a scope to maintain the quality of finished product after processing.

Identification of appropriate tools of information and communication ...

African Journals Online (AJOL)

Access to sufficient and desirable food is one of the principles of any developing and healthy society. One of the important means for attainment of food security is information and communication technologies (ICT). The purpose of the research was to identify appropriate tools of ICT in improving food security of Iran's rural ...

Usability principles to design mobile workplace learning content

Directory of Open Access Journals (Sweden)

Alessia Messuti

2015-04-01

Full Text Available The article describes the design of a mobile workplace learning tool for trainers of the International Training Centre of the International Labour Organization. The motivation behind is to provide trainers with a practical tool that will enable them to recall information at the moment of need and continue to learn in context. On this purpose a set of visual augmented reality cards was created, taking into consideration the fundamental mobile learning and usability principles. The nature of the article is empirical as it reports an experiment carried out with trainers which aimed at testing cards usability and learnability. Results show that the integration of both online and offline strategies was perceived as an added value as trainers could choose to retrieve information as they mostly like; finally, it also resulted in high usability scores, an aspect that contributes to their effectiveness at the workplace.

Mach's holographic principle

International Nuclear Information System (INIS)

Khoury, Justin; Parikh, Maulik

2009-01-01

Mach's principle is the proposition that inertial frames are determined by matter. We put forth and implement a precise correspondence between matter and geometry that realizes Mach's principle. Einstein's equations are not modified and no selection principle is applied to their solutions; Mach's principle is realized wholly within Einstein's general theory of relativity. The key insight is the observation that, in addition to bulk matter, one can also add boundary matter. Given a space-time, and thus the inertial frames, we can read off both boundary and bulk stress tensors, thereby relating matter and geometry. We consider some global conditions that are necessary for the space-time to be reconstructible, in principle, from bulk and boundary matter. Our framework is similar to that of the black hole membrane paradigm and, in asymptotically anti-de Sitter space-times, is consistent with holographic duality.

Cosmological principle

International Nuclear Information System (INIS)

Wesson, P.S.

1979-01-01

The Cosmological Principle states: the universe looks the same to all observers regardless of where they are located. To most astronomers today the Cosmological Principle means the universe looks the same to all observers because density of the galaxies is the same in all places. A new Cosmological Principle is proposed. It is called the Dimensional Cosmological Principle. It uses the properties of matter in the universe: density (rho), pressure (p), and mass (m) within some region of space of length (l). The laws of physics require incorporation of constants for gravity (G) and the speed of light (C). After combining the six parameters into dimensionless numbers, the best choices are: 8πGl 2 rho/c 2 , 8πGl 2 rho/c 4 , and 2 Gm/c 2 l (the Schwarzchild factor). The Dimensional Cosmological Principal came about because old ideas conflicted with the rapidly-growing body of observational evidence indicating that galaxies in the universe have a clumpy rather than uniform distribution

An all-optical system designed for the heating and temperature measurement of the diamond tool

CSIR Research Space (South Africa)

Masina, BN

2012-07-01

Full Text Available and then subsequent temperature measurement of the diamond tool. A laser beam was used as the source to raise the temperature of the diamond tool, and the resultant temperature was measured by using the blackbody principle. In this poster, we have successfully...

Principles for generation of time-dependent collimator settings during the LHC cycle

CERN Document Server

Bruce, R; Redaelli, S

2011-01-01

The settings of the LHC collimators have to be changed during the cycle of injection, ramp and squeeze to account for variations in the orbit, beam size and normalized distance to the beam center. We discuss the principles for how the settings are calculated and show a software tool that computes them as time-dependent functions from beambased data and theoretical optics models.

Putting Connectivist Principles into Practice: A Case Study of an Online Tertiary Course

Science.gov (United States)

Armatas, Christine; Spratt, Christine; Vincent, Andrew

2014-01-01

The Bachelor of Enterprise Learning is a newly accredited undergraduate degree where connectivist principles have been used to guide design of active, student-centered learning activities. A key feature of the curriculum is that it incorporates technology as both a source of information and a tool. Examples from this course are provided in this…

EnergiTools(R) - a power plant performance monitoring and diagnosis tool

International Nuclear Information System (INIS)

Ancion, P.V.; Bastien, R.; Ringdahl, K.

2000-01-01

Westinghouse EnergiTools(R) is a performance diagnostic tool for power generation plants that combines the power of on-line process data acquisition with advanced diagnostics methodologies. The system uses analytical models based on thermodynamic principles combined with knowledge of component diagnostic experts. An issue in modeling expert knowledge is to have a framework that can represent and process uncertainty in complex systems. In such experiments, it is nearly impossible to build deterministic models for the effects of faults on symptoms. A methodology based on causal probabilistic graphs, more specifically on Bayesian belief networks, has been implemented in EnergiTools(R) to capture the fault-symptom relationships. The methodology estimates the likelihood of the various component failures using the fault-symptom relationships. The system also has the ability to use neural networks for processes that are difficult to model analytically. An application is the estimation of the reactor power in nuclear power plant by interpreting several plant indicators. EnergiTools(R) is used for the on-line performance monitoring and diagnostics at Vattenfall Ringhals nuclear power plants in Sweden. It has led to the diagnosis of various performance issues with plant components. Two case studies are presented. In the first case, an overestimate of the thermal power due to a faulty instrument was found, which led to a plant operation below its optimal power. The paper shows how the problem was discovered, using the analytical thermodynamic calculations. The second case shows an application of EnergiTools(R) for the diagnostic of a condenser failure using causal probabilistic graphs

Supporting human performance in operations - principles for new nuclear build

International Nuclear Information System (INIS)

Lane, L.; Davey, E.

2006-01-01

Operational experience worldwide continues to demonstrate that human performance is a key factor in the ongoing safety, production, and protection of investment in operation of nuclear plants for electricity generation. Human performance in support of plant operational objectives can be influenced by a range of factors, for example: organizational culture and expectations; role assignments, training, and individual and team behaviours; and the support offered by the workplace environment, tools, and task design. This paper outlines a perspective on some of the principles that should be considered for application in the design of new nuclear build to facilitate support for human performance in plant operations. The principles identified focus on but are not limited to the tasks of shift staff, and are derived from the observations and experience of the authors who are experienced with control room operations in current plants. (author)

Supporting human performance in operations - principles for new nuclear build

Energy Technology Data Exchange (ETDEWEB)

Lane, L. [Ontario Power Generation, Darlington Nuclear Div., Bowmanville, Ontario (Canada); Davey, E. [Crew Systems Solutions, Deep River, Ontario (Canada)

2006-07-01

Operational experience worldwide continues to demonstrate that human performance is a key factor in the ongoing safety, production, and protection of investment in operation of nuclear plants for electricity generation. Human performance in support of plant operational objectives can be influenced by a range of factors, for example: organizational culture and expectations; role assignments, training, and individual and team behaviours; and the support offered by the workplace environment, tools, and task design. This paper outlines a perspective on some of the principles that should be considered for application in the design of new nuclear build to facilitate support for human performance in plant operations. The principles identified focus on but are not limited to the tasks of shift staff, and are derived from the observations and experience of the authors who are experienced with control room operations in current plants. (author)

Efficient prediction of human protein-protein interactions at a global scale.

Science.gov (United States)

Schoenrock, Andrew; Samanfar, Bahram; Pitre, Sylvain; Hooshyar, Mohsen; Jin, Ke; Phillips, Charles A; Wang, Hui; Phanse, Sadhna; Omidi, Katayoun; Gui, Yuan; Alamgir, Md; Wong, Alex; Barrenäs, Fredrik; Babu, Mohan; Benson, Mikael; Langston, Michael A; Green, James R; Dehne, Frank; Golshani, Ashkan

2014-12-10

Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods. On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments. The speed and accuracy associated with MP-PIPE can make this a potential tool to study individual human PPI networks (from genomic sequences alone) for personalized medicine.

AlphaSpace: Fragment-Centric Topographical Mapping To Target Protein–Protein Interaction Interfaces

Science.gov (United States)

2016-01-01

Inhibition of protein–protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structural characterization of the surface using geometry-based pocket-detection methods. An attractive mapping strategy—that builds on the principles of fragment-based drug discovery (FBDD)—is to detect the fragment-centric modularity at the protein surface and then characterize the large PPI interface as a set of localized, fragment-targetable interaction regions. Here, we introduce AlphaSpace, a computational analysis tool designed for fragment-centric topographical mapping (FCTM) of PPI interfaces. Our approach uses the alpha sphere construct, a geometric feature of a protein’s Voronoi diagram, to map out concave interaction space at the protein surface. We introduce two new features—alpha-atom and alpha-space—and the concept of the alpha-atom/alpha-space pair to rank pockets for fragment-targetability and to facilitate the evaluation of pocket/fragment complementarity. The resulting high-resolution interfacial map of targetable pocket space can be used to guide the rational design and optimization of small molecule or biomimetic PPI inhibitors. PMID:26225450

Ergonomic principles and tools for best interdisciplinary psycho-physical stress prevention.

Science.gov (United States)

Dal Cason, Dott Luigi

2012-01-01

The psycho-physical stress is a risk to all intents and purposes,finally acknowledged, it requires increasing attention. Measures forits protection are reflected in the appropriate application of organizational policies on a human scale, or in respect of the"macro-ergonomics". This work consists on several inter-disciplinary tools available to the proper prevention, outbreaks of work-related stress.During work, adequate rests are important to prevent work related physical and mental fatigue. The strategies for maintaining a healthy balance between work rate and work breaks, may differ depending on the individual, subjective habits and peculiarities related to the work environment. Resting does not necessarily mean "going to break". The break-time is important as the work-time. While the latter is regulated, the first is not always clearly defined, though necessary. Knowing the employment contract is the first step towards the implementation of their rights relating to periods of suspension from the activity of work is also essential for high performance working. Breathing exercises, massage therapy, biofeedback, role-playing are some of the tools used during work breaks to prevent mental and physical fatigue. At the end music has a rhythm by alternating strong and weak accents. If the musical notes represent the "vertical" trend of music (melody), figures and pauses, inserted into the rhythmic structure of the measure, regulate the duration of sounds over time and determine the "horizontal" trend of a song. Transferring this concept on work, is meant to understand, using a metaphor, the importance of respect of changes in both vertical and horizontal trends inside a cycle.

Proteins in vacuo. A more efficient means of calculating ...

African Journals Online (AJOL)

given bath gas particle and the protein. Calculations of savg. , though in principle straightforward, are time consuming. In the work presented below, it was investigated whether a more efficient calculation scheme can be employed without sacrificing too much accuracy. In the new scheme, atomic-scale protein surface ...

The Development of Protein Microarrays and Their Applications in DNA-Protein and Protein-Protein Interaction Analyses of Arabidopsis Transcription Factors

Science.gov (United States)

Gong, Wei; He, Kun; Covington, Mike; Dinesh-Kumar, S. P.; Snyder, Michael; Harmer, Stacey L.; Zhu, Yu-Xian; Deng, Xing Wang

2009-01-01

We used our collection of Arabidopsis transcription factor (TF) ORFeome clones to construct protein microarrays containing as many as 802 TF proteins. These protein microarrays were used for both protein-DNA and protein-protein interaction analyses. For protein-DNA interaction studies, we examined AP2/ERF family TFs and their cognate cis-elements. By careful comparison of the DNA-binding specificity of 13 TFs on the protein microarray with previous non-microarray data, we showed that protein microarrays provide an efficient and high throughput tool for genome-wide analysis of TF-DNA interactions. This microarray protein-DNA interaction analysis allowed us to derive a comprehensive view of DNA-binding profiles of AP2/ERF family proteins in Arabidopsis. It also revealed four TFs that bound the EE (evening element) and had the expected phased gene expression under clock-regulation, thus providing a basis for further functional analysis of their roles in clock regulation of gene expression. We also developed procedures for detecting protein interactions using this TF protein microarray and discovered four novel partners that interact with HY5, which can be validated by yeast two-hybrid assays. Thus, plant TF protein microarrays offer an attractive high-throughput alternative to traditional techniques for TF functional characterization on a global scale. PMID:19802365

Protein splicing and its evolution in eukaryotes

Directory of Open Access Journals (Sweden)

Starokadomskyy P. L.

2010-02-01

Full Text Available Inteins, or protein introns, are parts of protein sequences that are post-translationally excised, their flanking regions (exteins being spliced together. This process was called protein splicing. Originally inteins were found in prokaryotic or unicellular eukaryotic organisms. But the general principles of post-translation protein rearrangement are evolving yielding different post-translation modification of proteins in multicellular organisms. For clarity, these non-intein mediated events call either protein rearrangements or protein editing. The most intriguing example of protein editing is proteasome-mediated splicing of antigens in vertebrates that may play important role in antigen presentation. Other examples of protein rearrangements are maturation of Hg-proteins (critical receptors in embryogenesis as well as maturation of several metabolic enzymes. Despite a lack of experimental data we try to analyze some intriguing examples of protein splicing evolution.

Properties of gases, liquids, and solutions principles and methods

CERN Document Server

Mason, Warren P

2013-01-01

Physical Acoustics: Principles and Methods, Volume ll-Part A: Properties of Gases, Liquids, and Solutions ponders on high frequency sound waves in gases, liquids, and solids that have been proven as effective tools in examining the molecular, domain wall, and other types of motions. The selection first offers information on the transmission of sound waves in gases at very low pressures and the phenomenological theory of the relaxation phenomena in gases. Topics include free molecule propagation, phenomenological thermodynamics of irreversible processes, and simultaneous multiple relaxation pro

Quantum probability ranking principle for ligand-based virtual screening

Science.gov (United States)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening.

Science.gov (United States)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

BIPS: BIANA Interolog Prediction Server. A tool for protein-protein interaction inference.

Science.gov (United States)

Garcia-Garcia, Javier; Schleker, Sylvia; Klein-Seetharaman, Judith; Oliva, Baldo

2012-07-01

Protein-protein interactions (PPIs) play a crucial role in biology, and high-throughput experiments have greatly increased the coverage of known interactions. Still, identification of complete inter- and intraspecies interactomes is far from being complete. Experimental data can be complemented by the prediction of PPIs within an organism or between two organisms based on the known interactions of the orthologous genes of other organisms (interologs). Here, we present the BIANA (Biologic Interactions and Network Analysis) Interolog Prediction Server (BIPS), which offers a web-based interface to facilitate PPI predictions based on interolog information. BIPS benefits from the capabilities of the framework BIANA to integrate the several PPI-related databases. Additional metadata can be used to improve the reliability of the predicted interactions. Sensitivity and specificity of the server have been calculated using known PPIs from different interactomes using a leave-one-out approach. The specificity is between 72 and 98%, whereas sensitivity varies between 1 and 59%, depending on the sequence identity cut-off used to calculate similarities between sequences. BIPS is freely accessible at http://sbi.imim.es/BIPS.php.

Using continuous time stochastic modelling and nonparametric statistics to improve the quality of first principles models

DEFF Research Database (Denmark)

A methodology is presented that combines modelling based on first principles and data based modelling into a modelling cycle that facilitates fast decision-making based on statistical methods. A strong feature of this methodology is that given a first principles model along with process data......, the corresponding modelling cycle model of the given system for a given purpose. A computer-aided tool, which integrates the elements of the modelling cycle, is also presented, and an example is given of modelling a fed-batch bioreactor....

Protein structural similarity search by Ramachandran codes

Directory of Open Access Journals (Sweden)

Chang Chih-Hung

2007-08-01

Full Text Available Abstract Background Protein structural data has increased exponentially, such that fast and accurate tools are necessary to access structure similarity search. To improve the search speed, several methods have been designed to reduce three-dimensional protein structures to one-dimensional text strings that are then analyzed by traditional sequence alignment methods; however, the accuracy is usually sacrificed and the speed is still unable to match sequence similarity search tools. Here, we aimed to improve the linear encoding methodology and develop efficient search tools that can rapidly retrieve structural homologs from large protein databases. Results We propose a new linear encoding method, SARST (Structural similarity search Aided by Ramachandran Sequential Transformation. SARST transforms protein structures into text strings through a Ramachandran map organized by nearest-neighbor clustering and uses a regenerative approach to produce substitution matrices. Then, classical sequence similarity search methods can be applied to the structural similarity search. Its accuracy is similar to Combinatorial Extension (CE and works over 243,000 times faster, searching 34,000 proteins in 0.34 sec with a 3.2-GHz CPU. SARST provides statistically meaningful expectation values to assess the retrieved information. It has been implemented into a web service and a stand-alone Java program that is able to run on many different platforms. Conclusion As a database search method, SARST can rapidly distinguish high from low similarities and efficiently retrieve homologous structures. It demonstrates that the easily accessible linear encoding methodology has the potential to serve as a foundation for efficient protein structural similarity search tools. These search tools are supposed applicable to automated and high-throughput functional annotations or predictions for the ever increasing number of published protein structures in this post-genomic era.

EBIPM | Finding the Tools to Manage Invasive Annual Grasses

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management decisions for a given landscape based on ecological principles. Take a look at our video " Grass Management How much could prevention save you? Guidelines to Implement EBIPM Weed Prevention Areas Grass Facts/ID The EBIPM Model Crooked River Weed Management Area Guide Tools for Educators EBIPM High

High-Order Hamilton's Principle and the Hamilton's Principle of High-Order Lagrangian Function

International Nuclear Information System (INIS)

Zhao Hongxia; Ma Shanjun

2008-01-01

In this paper, based on the theorem of the high-order velocity energy, integration and variation principle, the high-order Hamilton's principle of general holonomic systems is given. Then, three-order Lagrangian equations and four-order Lagrangian equations are obtained from the high-order Hamilton's principle. Finally, the Hamilton's principle of high-order Lagrangian function is given.

Achieving Integration in Mixed Methods Designs—Principles and Practices

Science.gov (United States)

Fetters, Michael D; Curry, Leslie A; Creswell, John W

2013-01-01

Mixed methods research offers powerful tools for investigating complex processes and systems in health and health care. This article describes integration principles and practices at three levels in mixed methods research and provides illustrative examples. Integration at the study design level occurs through three basic mixed method designs—exploratory sequential, explanatory sequential, and convergent—and through four advanced frameworks—multistage, intervention, case study, and participatory. Integration at the methods level occurs through four approaches. In connecting, one database links to the other through sampling. With building, one database informs the data collection approach of the other. When merging, the two databases are brought together for analysis. With embedding, data collection and analysis link at multiple points. Integration at the interpretation and reporting level occurs through narrative, data transformation, and joint display. The fit of integration describes the extent the qualitative and quantitative findings cohere. Understanding these principles and practices of integration can help health services researchers leverage the strengths of mixed methods. PMID:24279835

A Practical Teaching Course in Directed Protein Evolution Using the Green Fluorescent Protein as a Model

Science.gov (United States)

Ruller, Roberto; Silva-Rocha, Rafael; Silva, Artur; Schneider, Maria Paula Cruz; Ward, Richard John

2011-01-01

Protein engineering is a powerful tool, which correlates protein structure with specific functions, both in applied biotechnology and in basic research. Here, we present a practical teaching course for engineering the green fluorescent protein (GFP) from "Aequorea victoria" by a random mutagenesis strategy using error-prone polymerase…

Designing a Tool for History Textbook Analysis

Directory of Open Access Journals (Sweden)

Katalin Eszter Morgan

2012-11-01

Full Text Available This article describes the process by which a five-dimensional tool for history textbook analysis was conceptualized and developed in three stages. The first stage consisted of a grounded theory approach to code the content of the sampled chapters of the books inductively. After that the findings from this coding process were combined with principles of text analysis as derived from the literature, specifically focusing on the notion of semiotic mediation as theorized by Lev VYGOTSKY. We explain how we then entered the third stage of the development of the tool, comprising five dimensions. Towards the end of the article we show how the tool could be adapted to serve other disciplines as well. The argument we forward in the article is for systematic and well theorized tools with which to investigate textbooks as semiotic mediators in education. By implication, textbook authors can also use these as guidelines. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs130170

Mining Proteomic Data to Expose Protein Modifications in Methanosarcina mazei strain Gö1

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Deborah eLeon

2015-03-01

Full Text Available Proteomic tools identify constituents of complex mixtures, often delivering long lists of identified proteins. The high-throughput methods excel at matching tandem mass spectrometry data to spectra predicted from sequence databases. Unassigned mass spectra are ignored, but could, in principle, provide valuable information on unanticipated modifications and improve protein annotations while consuming limited quantities of material. Strategies to mine information from these discards are presented, along with discussion of features that, when present, provide strong support for modifications. In this study we mined LC-MS/MS datasets of proteolytically-digested concanavalin A pull down fractions from Methanosarcina mazei Gö1 cell lysates. Analyses identified 154 proteins. Many of the observed proteins displayed post-translationally modified forms, including O-formylated and methyl-esterified segments that appear biologically relevant (i.e., not artifacts of sample handling. Interesting cleavages and modifications (e.g., S-cyanylation and trimethylation were observed near catalytic sites of methanogenesis enzymes. Of 31 Methanosarcina protein N-termini recovered by concanavalin A binding or from a previous study, only M. mazei S-layer protein MM1976 and its M. acetivorans C2A orthologue, MA0829, underwent signal peptide excision. Experimental results contrast with predictions from algorithms SignalP 3.0 and Exprot, which were found to over-predict the presence of signal peptides. Proteins MM0002, MM0716, MM1364, and MM1976 were found to be glycosylated, and employing chromatography tailored specifically for glycopeptides will likely reveal more.This study supplements limited, existing experimental datasets of mature archaeal N-termini, including presence or absence of signal peptides, translation initiation sites, and other processing. Methanosarcina surface and membrane proteins are richly modified.

Deciphering common recognition principles of nucleoside mono/di and tri-phosphates binding in diverse proteins via structural matching of their binding sites.

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Bhagavat, Raghu; Srinivasan, Narayanaswamy; Chandra, Nagasuma

2017-09-01

Nucleoside triphosphate (NTP) ligands are of high biological importance and are essential for all life forms. A pre-requisite for them to participate in diverse biochemical processes is their recognition by diverse proteins. It is thus of great interest to understand the basis for such recognition in different proteins. Towards this, we have used a structural bioinformatics approach and analyze structures of 4677 NTP complexes available in Protein Data Bank (PDB). Binding sites were extracted and compared exhaustively using PocketMatch, a sensitive in-house site comparison algorithm, which resulted in grouping the entire dataset into 27 site-types. Each of these site-types represent a structural motif comprised of two or more residue conservations, derived using another in-house tool for superposing binding sites, PocketAlign. The 27 site-types could be grouped further into 9 super-types by considering partial similarities in the sites, which indicated that the individual site-types comprise different combinations of one or more site features. A scan across PDB using the 27 structural motifs determined the motifs to be specific to NTP binding sites, and a computational alanine mutagenesis indicated that residues identified to be highly conserved in the motifs are also most contributing to binding. Alternate orientations of the ligand in several site-types were observed and rationalized, indicating the possibility of some residues serving as anchors for NTP recognition. The presence of multiple site-types and the grouping of multiple folds into each site-type is strongly suggestive of convergent evolution. Knowledge of determinants obtained from this study will be useful for detecting function in unknown proteins. Proteins 2017; 85:1699-1712. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The development of environmental assessment tools to support the creation of dementia friendly care environments: Innovative practice.

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Waller, Sarah; Masterson, Abigail; Evans, Simon C

2017-02-01

The need for more dementia friendly design in hospitals and other care settings is now widely acknowledged. Working with 26 NHS Trusts in England as part of a Department of Health commissioned programme, The King's Fund developed a set of overarching design principles and an environmental assessment tool for hospital wards in 2012. Following requests from other sectors, additional tools were developed for hospitals, care homes, health centres and housing with care. The tools have proven to be effective in both disseminating the principles of dementia friendly design and in enabling the case to be made for improvements that have a positive effect on patient outcomes and staff morale. This paper reports on the development, use and review of the environmental assessment tools, including further work that is now being taken forward by The Association for Dementia Studies, University of Worcester.

An Experiment on Creating Enterprise Specific BPM Languages and Tools

DEFF Research Database (Denmark)

Brahe, Steen

Many enterprises use their own domain concepts in modeling business process and use technology in specialized ways when they implement them in a Business Process Management (BPM) system.In contrast, BPM tools used for modeling and implementing business processes often provide a standard modeling...... and automation to BPM tools through a tool experiment in Danske Bank, a large financial institute; We develop business process modeling languages, tools and transformations that capture Danske Banks specific modeling concepts and use of technology, and which automate the generation of code. An empirical...... language, a standard implementation technology and a fixed transformation that may generate the implementation from the model. This makes the tools inflexible and difficult to use.This paper presents another approach. It applies the basic model driven development principles of direct representation...

SCit: web tools for protein side chain conformation analysis.

Science.gov (United States)

Gautier, R; Camproux, A-C; Tufféry, P

2004-07-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit.

Developing new chemical tools for solvent extraction

International Nuclear Information System (INIS)

Moyer, B.A.; Baes, C.F.; Burns, J.H.; Case, G.N.; Sachleben, R.A.; Bryan, S.A.; Lumetta, G.J.; McDowell, W.J.; Sachleben, R.A.

1993-01-01

Prospects for innovation and for greater technological impact in the field of solvent extraction (SX) seem as bright as ever, despite the maturation of SX as an economically significant separation method and as an important technique in the laboratory. New industrial, environmental, and analytical problems provide compelling motivation for diversifying the application of SX, developing new solvent systems, and seeking improved properties. Toward this end, basic research must be dedicated to enhancing the tools of SX: physical tools for probing the basis of extraction and molecular tools for developing new SX chemistries. In this paper, the authors describe their progress in developing and applying the general tools of equilibrium analysis and of ion recognition in SX. Nearly half a century after the field of SX began in earnest, coordination chemistry continues to provide the impetus for important advancements in understanding SX systems and in controlling SX chemistry. In particular, the physical tools of equilibrium analysis, X-ray crystallography, and spectroscopy are elucidating the molecular basis of SX in unprecedented detail. Moreover, the principles of ion recognition are providing the molecular tools with which to achieve new selectivities and new applications

Specificity and affinity quantification of protein-protein interactions.

Science.gov (United States)

Yan, Zhiqiang; Guo, Liyong; Hu, Liang; Wang, Jin

2013-05-01

Most biological processes are mediated by the protein-protein interactions. Determination of the protein-protein structures and insight into their interactions are vital to understand the mechanisms of protein functions. Currently, compared with the isolated protein structures, only a small fraction of protein-protein structures are experimentally solved. Therefore, the computational docking methods play an increasing role in predicting the structures and interactions of protein-protein complexes. The scoring function of protein-protein interactions is the key responsible for the accuracy of the computational docking. Previous scoring functions were mostly developed by optimizing the binding affinity which determines the stability of the protein-protein complex, but they are often lack of the consideration of specificity which determines the discrimination of native protein-protein complex against competitive ones. We developed a scoring function (named as SPA-PP, specificity and affinity of the protein-protein interactions) by incorporating both the specificity and affinity into the optimization strategy. The testing results and comparisons with other scoring functions show that SPA-PP performs remarkably on both predictions of binding pose and binding affinity. Thus, SPA-PP is a promising quantification of protein-protein interactions, which can be implemented into the protein docking tools and applied for the predictions of protein-protein structure and affinity. The algorithm is implemented in C language, and the code can be downloaded from http://dl.dropbox.com/u/1865642/Optimization.cpp.

A Novel Approach for Protein-Named Entity Recognition and Protein-Protein Interaction Extraction

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Meijing Li

2015-01-01

Full Text Available Many researchers focus on developing protein-named entity recognition (Protein-NER or PPI extraction systems. However, the studies about these two topics cannot be merged well; then existing PPI extraction systems’ Protein-NER still needs to improve. In this paper, we developed the protein-protein interaction extraction system named PPIMiner based on Support Vector Machine (SVM and parsing tree. PPIMiner consists of three main models: natural language processing (NLP model, Protein-NER model, and PPI discovery model. The Protein-NER model, which is named ProNER, identifies the protein names based on two methods: dictionary-based method and machine learning-based method. ProNER is capable of identifying more proteins than dictionary-based Protein-NER model in other existing systems. The final discovered PPIs extracted via PPI discovery model are represented in detail because we showed the protein interaction types and the occurrence frequency through two different methods. In the experiments, the result shows that the performances achieved by our ProNER and PPI discovery model are better than other existing tools. PPIMiner applied this protein-named entity recognition approach and parsing tree based PPI extraction method to improve the performance of PPI extraction. We also provide an easy-to-use interface to access PPIs database and an online system for PPIs extraction and Protein-NER.

Affinity purification combined with mass spectrometry to identify herpes simplex virus protein-protein interactions.

Science.gov (United States)

Meckes, David G

2014-01-01

The identification and characterization of herpes simplex virus protein interaction complexes are fundamental to understanding the molecular mechanisms governing the replication and pathogenesis of the virus. Recent advances in affinity-based methods, mass spectrometry configurations, and bioinformatics tools have greatly increased the quantity and quality of protein-protein interaction datasets. In this chapter, detailed and reliable methods that can easily be implemented are presented for the identification of protein-protein interactions using cryogenic cell lysis, affinity purification, trypsin digestion, and mass spectrometry.

Perceptual tools for quality-aware video networks

Science.gov (United States)

Bovik, A. C.

2014-01-01

Monitoring and controlling the quality of the viewing experience of videos transmitted over increasingly congested networks (especially wireless networks) is a pressing problem owing to rapid advances in video-centric mobile communication and display devices that are straining the capacity of the network infrastructure. New developments in automatic perceptual video quality models offer tools that have the potential to be used to perceptually optimize wireless video, leading to more efficient video data delivery and better received quality. In this talk I will review key perceptual principles that are, or could be used to create effective video quality prediction models, and leading quality prediction models that utilize these principles. The goal is to be able to monitor and perceptually optimize video networks by making them "quality-aware."

A Variation on Uncertainty Principle and Logarithmic Uncertainty Principle for Continuous Quaternion Wavelet Transforms

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Mawardi Bahri

2017-01-01

Full Text Available The continuous quaternion wavelet transform (CQWT is a generalization of the classical continuous wavelet transform within the context of quaternion algebra. First of all, we show that the directional quaternion Fourier transform (QFT uncertainty principle can be obtained using the component-wise QFT uncertainty principle. Based on this method, the directional QFT uncertainty principle using representation of polar coordinate form is easily derived. We derive a variation on uncertainty principle related to the QFT. We state that the CQWT of a quaternion function can be written in terms of the QFT and obtain a variation on uncertainty principle related to the CQWT. Finally, we apply the extended uncertainty principles and properties of the CQWT to establish logarithmic uncertainty principles related to generalized transform.

Biomedical engineering principles

CERN Document Server

Ritter, Arthur B; Valdevit, Antonio; Ascione, Alfred N

2011-01-01

Introduction: Modeling of Physiological ProcessesCell Physiology and TransportPrinciples and Biomedical Applications of HemodynamicsA Systems Approach to PhysiologyThe Cardiovascular SystemBiomedical Signal ProcessingSignal Acquisition and ProcessingTechniques for Physiological Signal ProcessingExamples of Physiological Signal ProcessingPrinciples of BiomechanicsPractical Applications of BiomechanicsBiomaterialsPrinciples of Biomedical Capstone DesignUnmet Clinical NeedsEntrepreneurship: Reasons why Most Good Designs Never Get to MarketAn Engineering Solution in Search of a Biomedical Problem

DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

Science.gov (United States)

Mistry, Divya; Wise, Roger P; Dickerson, Julie A

2017-01-01

Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be

The genetic difference principle.

Science.gov (United States)

Farrelly, Colin

2004-01-01

In the newly emerging debates about genetics and justice three distinct principles have begun to emerge concerning what the distributive aim of genetic interventions should be. These principles are: genetic equality, a genetic decent minimum, and the genetic difference principle. In this paper, I examine the rationale of each of these principles and argue that genetic equality and a genetic decent minimum are ill-equipped to tackle what I call the currency problem and the problem of weight. The genetic difference principle is the most promising of the three principles and I develop this principle so that it takes seriously the concerns of just health care and distributive justice in general. Given the strains on public funds for other important social programmes, the costs of pursuing genetic interventions and the nature of genetic interventions, I conclude that a more lax interpretation of the genetic difference principle is appropriate. This interpretation stipulates that genetic inequalities should be arranged so that they are to the greatest reasonable benefit of the least advantaged. Such a proposal is consistent with prioritarianism and provides some practical guidance for non-ideal societies--that is, societies that do not have the endless amount of resources needed to satisfy every requirement of justice.

Principles for a Code of Conduct for the Sustainable Management of Mangrove Ecosystems: A Work in Progress for Public Discussion

DEFF Research Database (Denmark)

Nielsen, Thomas

The Principles for a Code of Conduct for Sustainable Management of Mangrove Ecosystems is a guide to assist states, local and national non-governmental organizations and other stakeholders to develop cooperatively local codes, laws and/or regulations to protect mangroves and the critical functions......, grassroots organizations and other interested individuals and groups. The Principles were formulated based on a review of global mangrove management experience, about fifteen country case studies, including Auastralia, from all regions where mangroves exist, and seven regional workshops to date. The purpose...... of making a presentation on the Mangrove Principles at IMPAC is to gain additional feedback from interested stakeholders and experts, in particular, to provide inputs to the content of the Principles and recommendations for activities to promote their use as a management tool. The Principles and many...

FireProt: web server for automated design of thermostable proteins

Science.gov (United States)

Musil, Milos; Stourac, Jan; Brezovsky, Jan; Prokop, Zbynek; Zendulka, Jaroslav; Martinek, Tomas

2017-01-01

Abstract There is a continuous interest in increasing proteins stability to enhance their usability in numerous biomedical and biotechnological applications. A number of in silico tools for the prediction of the effect of mutations on protein stability have been developed recently. However, only single-point mutations with a small effect on protein stability are typically predicted with the existing tools and have to be followed by laborious protein expression, purification, and characterization. Here, we present FireProt, a web server for the automated design of multiple-point thermostable mutant proteins that combines structural and evolutionary information in its calculation core. FireProt utilizes sixteen tools and three protein engineering strategies for making reliable protein designs. The server is complemented with interactive, easy-to-use interface that allows users to directly analyze and optionally modify designed thermostable mutants. FireProt is freely available at http://loschmidt.chemi.muni.cz/fireprot. PMID:28449074

The XChemExplorer graphical workflow tool for routine or large-scale protein-ligand structure determination.

Science.gov (United States)

Krojer, Tobias; Talon, Romain; Pearce, Nicholas; Collins, Patrick; Douangamath, Alice; Brandao-Neto, Jose; Dias, Alexandre; Marsden, Brian; von Delft, Frank

2017-03-01

XChemExplorer (XCE) is a data-management and workflow tool to support large-scale simultaneous analysis of protein-ligand complexes during structure-based ligand discovery (SBLD). The user interfaces of established crystallographic software packages such as CCP4 [Winn et al. (2011), Acta Cryst. D67, 235-242] or PHENIX [Adams et al. (2010), Acta Cryst. D66, 213-221] have entrenched the paradigm that a `project' is concerned with solving one structure. This does not hold for SBLD, where many almost identical structures need to be solved and analysed quickly in one batch of work. Functionality to track progress and annotate structures is essential. XCE provides an intuitive graphical user interface which guides the user from data processing, initial map calculation, ligand identification and refinement up until data dissemination. It provides multiple entry points depending on the need of each project, enables batch processing of multiple data sets and records metadata, progress and annotations in an SQLite database. XCE is freely available and works on any Linux and Mac OS X system, and the only dependency is to have the latest version of CCP4 installed. The design and usage of this tool are described here, and its usefulness is demonstrated in the context of fragment-screening campaigns at the Diamond Light Source. It is routinely used to analyse projects comprising 1000 data sets or more, and therefore scales well to even very large ligand-design projects.

Variational principles for collective motion: Relation between invariance principle of the Schroedinger equation and the trace variational principle

International Nuclear Information System (INIS)

Klein, A.; Tanabe, K.

1984-01-01

The invariance principle of the Schroedinger equation provides a basis for theories of collective motion with the help of the time-dependent variational principle. It is formulated here with maximum generality, requiring only the motion of intrinsic state in the collective space. Special cases arise when the trial vector is a generalized coherent state and when it is a uniform superposition of collective eigenstates. The latter example yields variational principles uncovered previously only within the framework of the equations of motion method. (orig.)

Operational and Strategic Controlling Tools in Microenterprises - Case Study

Science.gov (United States)

Konsek-Ciechońska, Justyna

2017-12-01

Globalisation and increasing requirements of the environment cause the executives and supervisors to search for more and more perfect solutions, allowing them to streamline and improve the effectiveness of company operations. One of such tools, used more and more often, is controlling, the role of which has substantially increased in the recent years. It is already implemented not only in large companies with foreign capital, but also in increasingly smaller entities, which begin to notice the positive effects of the implications of the principles and tools of controlling - both operational and strategic. The purpose of the article is to demonstrate the practical side of controlling tools that can be used for the purposes of operations conducted by microenterprises.

Prediction of the Ebola Virus Infection Related Human Genes Using Protein-Protein Interaction Network.

Science.gov (United States)

Cao, HuanHuan; Zhang, YuHang; Zhao, Jia; Zhu, Liucun; Wang, Yi; Li, JiaRui; Feng, Yuan-Ming; Zhang, Ning

2017-01-01

Ebola hemorrhagic fever (EHF) is caused by Ebola virus (EBOV). It is reported that human could be infected by EBOV with a high fatality rate. However, association factors between EBOV and host still tend to be ambiguous. According to the "guilt by association" (GBA) principle, proteins interacting with each other are very likely to function similarly or the same. Based on this assumption, we tried to obtain EBOV infection-related human genes in a protein-protein interaction network using Dijkstra algorithm. We hope it could contribute to the discovery of novel effective treatments. Finally, 15 genes were selected as potential EBOV infection-related human genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The evolution of CACSD tools-a software engineering perspective

DEFF Research Database (Denmark)

Ravn, Ole; Szymkat, Maciej

1992-01-01

The earlier evolution of computer-aided control system design (CACSD) tools is discussed from a software engineering perspective. A model of the design process is presented as the basis for principles and requirements of future CACSD tools. Combinability, interfacing in memory, and an open...... workspace are seen as important concepts in CACSD. Some points are made about the problem of buy or make when new software is required, and the idea of buy and make is put forward. Emphasis is put on the time perspective and the life cycle of the software...

The use of ultrasound for decontamination of tools and equipment in nuclear power plant Krshko

International Nuclear Information System (INIS)

Erman, R.

1987-01-01

This paper describes the main principles of the ultrasonic generator functioning and the use of ultrasound for decontamination of tools and equipment in nuclear power plant Krshko. The paper gives the operating procedure and presents decontamination results of tools and equipment fabricated from various materials. (author) 3 refs.; 1 tab

Understanding water equilibration fundamentals as a step for rational protein crystallization.

Directory of Open Access Journals (Sweden)

Pedro M Martins

Full Text Available BACKGROUND: Vapor diffusion is the most widely used technique for protein crystallization and the rate of water evaporation plays a key role on the quality of the crystals. Attempts have been made in the past to solve the mass transfer problem governing the evaporation process, either analytically or by employing numerical methods. Despite these efforts, the methods used for protein crystallization remain based on trial and error techniques rather than on fundamental principles. METHODOLOGY/PRINCIPAL FINDINGS: Here we present a new theoretical model which describes the hanging drop method as a function of the different variables that are known to influence the evaporation process. The model is extensively tested against experimental data published by other authors and considering different crystallizing conditions. Aspects responsible for the discrepancies between the existing theories and the measured evaporation kinetics are especially discussed; they include the characterization of vapor-liquid equilibrium, the role of mass transfer within the evaporating droplet, and the influence of the droplet-reservoir distance. CONCLUSIONS/SIGNIFICANCE: The validation tests show that the proposed model can be used to predict the water evaporation rates under a wide range of experimental conditions used in the hanging drop vapor-diffusion method, with no parameter fitting or computational requirements. This model combined with protein solubility data is expected to become a useful tool for a priori screening of crystallization conditions.

Core principles of evolutionary medicine

Science.gov (United States)

Grunspan, Daniel Z; Nesse, Randolph M; Barnes, M Elizabeth; Brownell, Sara E

2018-01-01

Abstract Background and objectives Evolutionary medicine is a rapidly growing field that uses the principles of evolutionary biology to better understand, prevent and treat disease, and that uses studies of disease to advance basic knowledge in evolutionary biology. Over-arching principles of evolutionary medicine have been described in publications, but our study is the first to systematically elicit core principles from a diverse panel of experts in evolutionary medicine. These principles should be useful to advance recent recommendations made by The Association of American Medical Colleges and the Howard Hughes Medical Institute to make evolutionary thinking a core competency for pre-medical education. Methodology The Delphi method was used to elicit and validate a list of core principles for evolutionary medicine. The study included four surveys administered in sequence to 56 expert panelists. The initial open-ended survey created a list of possible core principles; the three subsequent surveys winnowed the list and assessed the accuracy and importance of each principle. Results Fourteen core principles elicited at least 80% of the panelists to agree or strongly agree that they were important core principles for evolutionary medicine. These principles over-lapped with concepts discussed in other articles discussing key concepts in evolutionary medicine. Conclusions and implications This set of core principles will be helpful for researchers and instructors in evolutionary medicine. We recommend that evolutionary medicine instructors use the list of core principles to construct learning goals. Evolutionary medicine is a young field, so this list of core principles will likely change as the field develops further. PMID:29493660

Proteins of unknown function in the Protein Data Bank (PDB): an inventory of true uncharacterized proteins and computational tools for their analysis.

Science.gov (United States)

Nadzirin, Nurul; Firdaus-Raih, Mohd

2012-10-08

Proteins of uncharacterized functions form a large part of many of the currently available biological databases and this situation exists even in the Protein Data Bank (PDB). Our analysis of recent PDB data revealed that only 42.53% of PDB entries (1084 coordinate files) that were categorized under "unknown function" are true examples of proteins of unknown function at this point in time. The remainder 1465 entries also annotated as such appear to be able to have their annotations re-assessed, based on the availability of direct functional characterization experiments for the protein itself, or for homologous sequences or structures thus enabling computational function inference.

Proteins of Unknown Function in the Protein Data Bank (PDB: An Inventory of True Uncharacterized Proteins and Computational Tools for Their Analysis

Directory of Open Access Journals (Sweden)

Nurul Nadzirin

2012-10-01

Full Text Available Proteins of uncharacterized functions form a large part of many of the currently available biological databases and this situation exists even in the Protein Data Bank (PDB. Our analysis of recent PDB data revealed that only 42.53% of PDB entries (1084 coordinate files that were categorized under “unknown function” are true examples of proteins of unknown function at this point in time. The remainder 1465 entries also annotated as such appear to be able to have their annotations re-assessed, based on the availability of direct functional characterization experiments for the protein itself, or for homologous sequences or structures thus enabling computational function inference.

ProClaT, a new bioinformatics tool for in silico protein reclassification: case study of DraB, a protein coded from the draTGB operon in Azospirillum brasilense.

Science.gov (United States)

Rubel, Elisa Terumi; Raittz, Roberto Tadeu; Coimbra, Nilson Antonio da Rocha; Gehlen, Michelly Alves Coutinho; Pedrosa, Fábio de Oliveira

2016-12-15

Azopirillum brasilense is a plant-growth promoting nitrogen-fixing bacteria that is used as bio-fertilizer in agriculture. Since nitrogen fixation has a high-energy demand, the reduction of N 2 to NH 4 + by nitrogenase occurs only under limiting conditions of NH 4 + and O 2 . Moreover, the synthesis and activity of nitrogenase is highly regulated to prevent energy waste. In A. brasilense nitrogenase activity is regulated by the products of draG and draT. The product of the draB gene, located downstream in the draTGB operon, may be involved in the regulation of nitrogenase activity by an, as yet, unknown mechanism. A deep in silico analysis of the product of draB was undertaken aiming at suggesting its possible function and involvement with DraT and DraG in the regulation of nitrogenase activity in A. brasilense. In this work, we present a new artificial intelligence strategy for protein classification, named ProClaT. The features used by the pattern recognition model were derived from the primary structure of the DraB homologous proteins, calculated by a ProClaT internal algorithm. ProClaT was applied to this case study and the results revealed that the A. brasilense draB gene codes for a protein highly similar to the nitrogenase associated NifO protein of Azotobacter vinelandii. This tool allowed the reclassification of DraB/NifO homologous proteins, hypothetical, conserved hypothetical and those annotated as putative arsenate reductase, ArsC, as NifO-like. An analysis of co-occurrence of draB, draT, draG and of other nif genes was performed, suggesting the involvement of draB (nifO) in nitrogen fixation, however, without the definition of a specific function.

A database and tool, IM Browser, for exploring and integrating emerging gene and protein interaction data for Drosophila

Directory of Open Access Journals (Sweden)

Parrish Jodi R

2006-04-01

Full Text Available Abstract Background Biological processes are mediated by networks of interacting genes and proteins. Efforts to map and understand these networks are resulting in the proliferation of interaction data derived from both experimental and computational techniques for a number of organisms. The volume of this data combined with the variety of specific forms it can take has created a need for comprehensive databases that include all of the available data sets, and for exploration tools to facilitate data integration and analysis. One powerful paradigm for the navigation and analysis of interaction data is an interaction graph or map that represents proteins or genes as nodes linked by interactions. Several programs have been developed for graphical representation and analysis of interaction data, yet there remains a need for alternative programs that can provide casual users with rapid easy access to many existing and emerging data sets. Description Here we describe a comprehensive database of Drosophila gene and protein interactions collected from a variety of sources, including low and high throughput screens, genetic interactions, and computational predictions. We also present a program for exploring multiple interaction data sets and for combining data from different sources. The program, referred to as the Interaction Map (IM Browser, is a web-based application for searching and visualizing interaction data stored in a relational database system. Use of the application requires no downloads and minimal user configuration or training, thereby enabling rapid initial access to interaction data. IM Browser was designed to readily accommodate and integrate new types of interaction data as it becomes available. Moreover, all information associated with interaction measurements or predictions and the genes or proteins involved are accessible to the user. This allows combined searches and analyses based on either common or technique-specific attributes

Three-dimensional protein structure prediction: Methods and computational strategies.

Science.gov (United States)

Dorn, Márcio; E Silva, Mariel Barbachan; Buriol, Luciana S; Lamb, Luis C

2014-10-12

A long standing problem in structural bioinformatics is to determine the three-dimensional (3-D) structure of a protein when only a sequence of amino acid residues is given. Many computational methodologies and algorithms have been proposed as a solution to the 3-D Protein Structure Prediction (3-D-PSP) problem. These methods can be divided in four main classes: (a) first principle methods without database information; (b) first principle methods with database information; (c) fold recognition and threading methods; and (d) comparative modeling methods and sequence alignment strategies. Deterministic computational techniques, optimization techniques, data mining and machine learning approaches are typically used in the construction of computational solutions for the PSP problem. Our main goal with this work is to review the methods and computational strategies that are currently used in 3-D protein prediction. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Principle and the Method of the Radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Kurata, Kunio [Dainabot Radioisotope Laboratory, Tokyo (Japan)

1970-03-15

The measurements of the amounts of various hormones in the body is one of the most important subjects in the field of endocrinology. The result obtained is not only helpful for the basic studies, such as the function studies of each organ or their interrelationship, but also valuable for routine clinical diagnosis. For the most of peptide hormones or protein hormones, a chemical measurement is very difficult. Biological methods are mostly utilized for this purpose but are not always satisfactory. The use of labeled hormone in combination with its antiserum led to the highly specific and sensitive measurement of the hormone in human plasma. This method is based essentially on the principle of isotope dilution method and is called radioimmunoassay. From the nuclear medical aspect, this is now one of the major fields of in vitro assay with radioisotope. With this method, less than 1 micro unit of insulin per ml of serum can be detected. In this lecture, I would like to talk about the principle and the method of the radioimmunoassay.

Tools for open geospatial science

Science.gov (United States)

Petras, V.; Petrasova, A.; Mitasova, H.

2017-12-01

Open science uses open source to deal with reproducibility challenges in data and computational sciences. However, just using open source software or making the code public does not make the research reproducible. Moreover, the scientists face the challenge of learning new unfamiliar tools and workflows. In this contribution, we will look at a graduate-level course syllabus covering several software tools which make validation and reuse by a wider professional community possible. For the novices in the open science arena, we will look at how scripting languages such as Python and Bash help us reproduce research (starting with our own work). Jupyter Notebook will be introduced as a code editor, data exploration tool, and a lab notebook. We will see how Git helps us not to get lost in revisions and how Docker is used to wrap all the parts together using a single text file so that figures for a scientific paper or a technical report can be generated with a single command. We will look at examples of software and publications in the geospatial domain which use these tools and principles. Scientific contributions to GRASS GIS, a powerful open source desktop GIS and geoprocessing backend, will serve as an example of why and how to publish new algorithms and tools as part of a bigger open source project.

TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics.

Science.gov (United States)

Parra, R Gonzalo; Schafer, Nicholas P; Radusky, Leandro G; Tsai, Min-Yeh; Guzovsky, A Brenda; Wolynes, Peter G; Ferreiro, Diego U

2016-07-08

The protein frustratometer is an energy landscape theory-inspired algorithm that aims at localizing and quantifying the energetic frustration present in protein molecules. Frustration is a useful concept for analyzing proteins' biological behavior. It compares the energy distributions of the native state with respect to structural decoys. The network of minimally frustrated interactions encompasses the folding core of the molecule. Sites of high local frustration often correlate with functional regions such as binding sites and regions involved in allosteric transitions. We present here an upgraded version of a webserver that measures local frustration. The new implementation that allows the inclusion of electrostatic energy terms, important to the interactions with nucleic acids, is significantly faster than the previous version enabling the analysis of large macromolecular complexes within a user-friendly interface. The webserver is freely available at URL: http://frustratometer.qb.fcen.uba.ar. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

The certainty principle (review)

OpenAIRE

Arbatsky, D. A.

2006-01-01

The certainty principle (2005) allowed to conceptualize from the more fundamental grounds both the Heisenberg uncertainty principle (1927) and the Mandelshtam-Tamm relation (1945). In this review I give detailed explanation and discussion of the certainty principle, oriented to all physicists, both theorists and experimenters.

Fusion research principles

CERN Document Server

Dolan, Thomas James

2013-01-01

Fusion Research, Volume I: Principles provides a general description of the methods and problems of fusion research. The book contains three main parts: Principles, Experiments, and Technology. The Principles part describes the conditions necessary for a fusion reaction, as well as the fundamentals of plasma confinement, heating, and diagnostics. The Experiments part details about forty plasma confinement schemes and experiments. The last part explores various engineering problems associated with reactor design, vacuum and magnet systems, materials, plasma purity, fueling, blankets, neutronics

BACHSCORE. A tool for evaluating efficiently and reliably the quality of large sets of protein structures

Science.gov (United States)

Sarti, E.; Zamuner, S.; Cossio, P.; Laio, A.; Seno, F.; Trovato, A.

2013-12-01

In protein structure prediction it is of crucial importance, especially at the refinement stage, to score efficiently large sets of models by selecting the ones that are closest to the native state. We here present a new computational tool, BACHSCORE, that allows its users to rank different structural models of the same protein according to their quality, evaluated by using the BACH++ (Bayesian Analysis Conformation Hunt) scoring function. The original BACH statistical potential was already shown to discriminate with very good reliability the protein native state in large sets of misfolded models of the same protein. BACH++ features a novel upgrade in the solvation potential of the scoring function, now computed by adapting the LCPO (Linear Combination of Pairwise Orbitals) algorithm. This change further enhances the already good performance of the scoring function. BACHSCORE can be accessed directly through the web server: bachserver.pd.infn.it. Catalogue identifier: AEQD_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEQD_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 3 No. of lines in distributed program, including test data, etc.: 130159 No. of bytes in distributed program, including test data, etc.: 24 687 455 Distribution format: tar.gz Programming language: C++. Computer: Any computer capable of running an executable produced by a g++ compiler (4.6.3 version). Operating system: Linux, Unix OS-es. RAM: 1 073 741 824 bytes Classification: 3. Nature of problem: Evaluate the quality of a protein structural model, taking into account the possible “a priori” knowledge of a reference primary sequence that may be different from the amino-acid sequence of the model; the native protein structure should be recognized as the best model. Solution method: The contact potential scores the occurrence of any given type of residue pair in 5 possible

A Fast Inspection of Tool Electrode and Drilling Depth in EDM Drilling by Detection Line Algorithm.

Science.gov (United States)

Huang, Kuo-Yi

2008-08-21

The purpose of this study was to develop a novel measurement method using a machine vision system. Besides using image processing techniques, the proposed system employs a detection line algorithm that detects the tool electrode length and drilling depth of a workpiece accurately and effectively. Different boundaries of areas on the tool electrode are defined: a baseline between base and normal areas, a ND-line between normal and drilling areas (accumulating carbon area), and a DD-line between drilling area and dielectric fluid droplet on the electrode tip. Accordingly, image processing techniques are employed to extract a tool electrode image, and the centroid, eigenvector, and principle axis of the tool electrode are determined. The developed detection line algorithm (DLA) is then used to detect the baseline, ND-line, and DD-line along the direction of the principle axis. Finally, the tool electrode length and drilling depth of the workpiece are estimated via detected baseline, ND-line, and DD-line. Experimental results show good accuracy and efficiency in estimation of the tool electrode length and drilling depth under different conditions. Hence, this research may provide a reference for industrial application in EDM drilling measurement.

Biochemical principles underlying the stable maintenance of LTP by the CaMKII/NMDAR complex.

Science.gov (United States)

Lisman, John; Raghavachari, Sridhar

2015-09-24

Memory involves the storage of information at synapses by an LTP-like process. This information storage is synapse specific and can endure for years despite the turnover of all synaptic proteins. There must, therefore, be special principles that underlie the stability of LTP. Recent experimental results suggest that LTP is maintained by the complex of CaMKII with the NMDAR. Here we consider the specifics of the CaMKII/NMDAR molecular switch, with the goal of understanding the biochemical principles that underlie stable information storage by synapses. Consideration of a variety of experimental results suggests that multiple principles are involved. One switch requirement is to prevent spontaneous transitions from the off to the on state. The highly cooperative nature of CaMKII autophosphorylation by Ca(2+) (Hill coefficient of 8) and the fact that formation of the CaMKII/NMDAR complex requires release of CaMKII from actin are mechanisms that stabilize the off state. The stability of the on state depends critically on intersubunit autophosphorylation, a process that restores any loss of pT286 due to phosphatase activity. Intersubunit autophosphorylation is also important in explaining why on state stability is not compromised by protein turnover. Recent evidence suggests that turnover occurs by subunit exchange. Thus, stability could be achieved if a newly inserted unphosphorylated subunit was autophosphorylated by a neighboring subunit. Based on other recent work, we posit a novel mechanism that enhances the stability of the on state by protection of pT286 from phosphatases. We posit that the binding of the NMNDAR to CaMKII forces pT286 into the catalytic site of a neighboring subunit, thereby protecting pT286 from phosphatases. A final principle concerns the role of structural changes. The binding of CaMKII to the NMDAR may act as a tag to organize the binding of further proteins that produce the synapse enlargement that underlies late LTP. We argue that these

Photo-oxidation of proteins and its role in cataractogenesis

DEFF Research Database (Denmark)

Davies, Michael Jonathan; Truscott, R J

2001-01-01

by the protein, or bound chromophore groups, thereby generating excited states (singlet or triplets) or radicals via photo-ionisation. The second major process involves indirect oxidation of the protein via the formation and subsequent reactions of singlet oxygen generated by the transfer of energy to ground...... state (triplet) molecular oxygen by either protein-bound, or other, chromophores. The basic principles behind these mechanisms of photo-oxidation of amino acids, peptides and proteins and the potential selectivity of damage are discussed. Emphasis is placed primarily on the intermediates...

Database principles programming performance

CERN Document Server

O'Neil, Patrick

2014-01-01

Database: Principles Programming Performance provides an introduction to the fundamental principles of database systems. This book focuses on database programming and the relationships between principles, programming, and performance.Organized into 10 chapters, this book begins with an overview of database design principles and presents a comprehensive introduction to the concepts used by a DBA. This text then provides grounding in many abstract concepts of the relational model. Other chapters introduce SQL, describing its capabilities and covering the statements and functions of the programmi

Statistical Analysis of Protein Ensembles

Science.gov (United States)

Máté, Gabriell; Heermann, Dieter

2014-04-01

As 3D protein-configuration data is piling up, there is an ever-increasing need for well-defined, mathematically rigorous analysis approaches, especially that the vast majority of the currently available methods rely heavily on heuristics. We propose an analysis framework which stems from topology, the field of mathematics which studies properties preserved under continuous deformations. First, we calculate a barcode representation of the molecules employing computational topology algorithms. Bars in this barcode represent different topological features. Molecules are compared through their barcodes by statistically determining the difference in the set of their topological features. As a proof-of-principle application, we analyze a dataset compiled of ensembles of different proteins, obtained from the Ensemble Protein Database. We demonstrate that our approach correctly detects the different protein groupings.

Biophysics of protein evolution and evolutionary protein biophysics

Science.gov (United States)

Sikosek, Tobias; Chan, Hue Sun

2014-01-01

The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence–structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by ‘hidden’ conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution. PMID:25165599

A Novel Physical Sensing Principle for Liquid Characterization Using Paper-Based Hygro-Mechanical Systems (PB-HMS).

Science.gov (United States)

Perez-Cruz, Angel; Stiharu, Ion; Dominguez-Gonzalez, Aurelio

2017-07-20

In recent years paper-based microfluidic systems have emerged as versatile tools for developing sensors in different areas. In this work; we report a novel physical sensing principle for the characterization of liquids using a paper-based hygro-mechanical system (PB-HMS). The PB-HMS is formed by the interaction of liquid droplets and paper-based mini-structures such as cantilever beams. The proposed principle takes advantage of the hygroscopic properties of paper to produce hygro-mechanical motion. The dynamic response of the PB-HMS reveals information about the tested liquid that can be applied to characterize certain properties of liquids. A suggested method to characterize liquids by means of the proposed principle is introduced. The experimental results show the feasibility of such a method. It is expected that the proposed principle may be applied to sense properties of liquids in different applications where both disposability and portability are of extreme importance.

Plant plasma membrane 14-3-3 proteins differ in solubility and form fusicoccin-dependent complexes

NARCIS (Netherlands)

Korthout, H.A.A.J.; de Boer, A.H.

1998-01-01

The binding protein for the phytotoxin fusicoccin belongs to the class of highly conserved 14-3-3 proteins. A general principle for the mode of action of 14-3-3 proteins is that they serve as docking clamps in order to facilitate protein interactions. This implies that 14-3-3 proteins may behave

Transforming Mobile Platform with KI-SIM Card into an Open Mobile Identity Tool

Science.gov (United States)

Hyppönen, Konstantin; Hassinen, Marko; Trichina, Elena

Recent introduction of Near Field Communication (NFC) in mobile phones has stimulated the development of new proximity payment and identification services. We present an architecture that facilitates the use of the mobile phone as a personalised electronic identity tool. The tool can work as a replacement for numerous ID cards and licenses. Design for privacy principles have been applied, such as minimisation of data collection and informed consent of the user. We describe an implementation of a lightweight version of the of the mobile identity tool using currently available handset technology and off-the-shelf development tools.

Software tool for data mining and its applications

Science.gov (United States)

Yang, Jie; Ye, Chenzhou; Chen, Nianyi

2002-03-01

A software tool for data mining is introduced, which integrates pattern recognition (PCA, Fisher, clustering, hyperenvelop, regression), artificial intelligence (knowledge representation, decision trees), statistical learning (rough set, support vector machine), computational intelligence (neural network, genetic algorithm, fuzzy systems). It consists of nine function models: pattern recognition, decision trees, association rule, fuzzy rule, neural network, genetic algorithm, Hyper Envelop, support vector machine, visualization. The principle and knowledge representation of some function models of data mining are described. The software tool of data mining is realized by Visual C++ under Windows 2000. Nonmonotony in data mining is dealt with by concept hierarchy and layered mining. The software tool of data mining has satisfactorily applied in the prediction of regularities of the formation of ternary intermetallic compounds in alloy systems, and diagnosis of brain glioma.

PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs

Directory of Open Access Journals (Sweden)

Greenblatt Jack

2006-07-01

Full Text Available Abstract Background Identification of protein interaction networks has received considerable attention in the post-genomic era. The currently available biochemical approaches used to detect protein-protein interactions are all time and labour intensive. Consequently there is a growing need for the development of computational tools that are capable of effectively identifying such interactions. Results Here we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins. PIPE showed a sensitivity of 61% for detecting any yeast protein interaction with 89% specificity and an overall accuracy of 75%. This rate of success is comparable to those associated with the most commonly used biochemical techniques. Using PIPE, we identified a novel interaction between YGL227W (vid30 and YMR135C (gid8 yeast proteins. This lead us to the identification of a novel yeast complex that here we term vid30 complex (vid30c. The observed interaction was confirmed by tandem affinity purification (TAP tag, verifying the ability of PIPE to predict novel protein-protein interactions. We then used PIPE analysis to investigate the internal architecture of vid30c. It appeared from PIPE analysis that vid30c may consist of a core and a secondary component. Generation of yeast gene deletion strains combined with TAP tagging analysis indicated that the deletion of a member of the core component interfered with the formation of vid30c, however, deletion of a member of the secondary component had little effect (if any on the formation of vid30c. Also, PIPE can be used to analyse yeast proteins for which TAP tagging fails, thereby allowing us to predict protein interactions that are not

Application of the Total Quality Management Approach Principles and the ISO 9000 Standards in Engineering Education.

Science.gov (United States)

Waks, Shlomo; Frank, Moti

1999-01-01

Discusses the applicability of the definition, principles, and underlying strategies of total quality management (TQM) for engineering education. Describes several tools and methods for the implementation of TQM and its suitability for a variety of school activities. Presents a TQM course outline combining lectures, discussions, suggested…

Design tools for complex dynamic security systems.

Energy Technology Data Exchange (ETDEWEB)

Byrne, Raymond Harry; Rigdon, James Brian; Rohrer, Brandon Robinson; Laguna, Glenn A.; Robinett, Rush D. III (.; ); Groom, Kenneth Neal; Wilson, David Gerald; Bickerstaff, Robert J.; Harrington, John J.

2007-01-01

The development of tools for complex dynamic security systems is not a straight forward engineering task but, rather, a scientific task where discovery of new scientific principles and math is necessary. For years, scientists have observed complex behavior but have had difficulty understanding it. Prominent examples include: insect colony organization, the stock market, molecular interactions, fractals, and emergent behavior. Engineering such systems will be an even greater challenge. This report explores four tools for engineered complex dynamic security systems: Partially Observable Markov Decision Process, Percolation Theory, Graph Theory, and Exergy/Entropy Theory. Additionally, enabling hardware technology for next generation security systems are described: a 100 node wireless sensor network, unmanned ground vehicle and unmanned aerial vehicle.

Ordinary differential equations principles and applications

CERN Document Server

Nandakumaran, A K; George, Raju K

2017-01-01

Written in a clear, logical and concise manner, this comprehensive resource allows students to quickly understand the key principles, techniques and applications of ordinary differential equations. Important topics including first and second order linear equations, initial value problems and qualitative theory are presented in separate chapters. The concepts of two point boundary value problems, physical models and first order partial differential equations are discussed in detail. The text uses tools of calculus and real analysis to get solutions in explicit form. While discussing first order linear systems, linear algebra techniques are used. The real-life applications are interspersed throughout the book to invoke reader's interest. The methods and tricks to solve numerous mathematical problems with sufficient derivations and explanation are provided. The proofs of theorems are explained for the benefit of the readers.

Deploying Renewables: Principles for Effective Policies. Executive Summary [Russian Version

Energy Technology Data Exchange (ETDEWEB)

NONE

2008-07-01

Renewable energy can play a fundamental role in tackling climate change, environmental degradation and energy security. As these challenges have become ever more pressing, governments and markets are seeking innovative solutions. Yet, what are the key factors that will determine the success of renewable energy policies? How can current policies be improved to encourage greater deployment of renewables? What impact can more effective policies have on renewables’ share in the future global energy mix and how soon? Deploying Renewables: Principles for Effective Policies addresses these questions. Responding to the Gleneagles G8 call for a clean and secure energy future, it highlights key policy tools to fast-track renewables into the mainstream. This analysis illustrates good practices by applying the combined metrics of effectiveness and efficiency to renewable energy policies in the electricity, heating and transport sectors. It highlights significant barriers to accelerating renewables penetration, and argues that the great potential of renewables can be exploited much more rapidly and to a much larger extent if good practices are adopted. Carefully designed policy frameworks, customised to support technologies at differing stages of maturity, will deliver a strong portfolio of renewable energy technologies. Deploying Renewables: Principles for Effective Policies provides recommendations on key principles for policy design as a template for decision makers.

Radiation protection principles

International Nuclear Information System (INIS)

Ismail Bahari

2007-01-01

The presentation outlines the aspects of radiation protection principles. It discussed the following subjects; radiation hazards and risk, the objectives of radiation protection, three principles of the system - justification of practice, optimization of protection and safety, dose limit

The principle(s) of co-existence in Europe: Social, economic and legal avenues

NARCIS (Netherlands)

Purnhagen, K.; Wesseler, J.H.H.

2015-01-01

The European policy of coexistence follows a number of well-established social, economic and legal principles. Applying these principles in practice has resulted in a complex “rag rug” of coexistence policies in Europe. This rag rug makes enforcement of these principles difficult, at times even

Targeted proteomics as a tool for porcine acute phase proteins measurements

DEFF Research Database (Denmark)

Marco-Ramell, Anna; Bassols, Anna; Bislev, Stine Lønnerup

2013-01-01

. Selected reaction monitoring (SRM), a targeted quantitative proteomic technique, may be used as an alternative to commercial kits for the measurement and validation of target proteins. Acute phase proteins (APPs) are widely recognized inflammation and infection biomarkers (Eckersall, 2010...

Proof of principle for epitope-focused vaccine design

Science.gov (United States)

Correia, Bruno E.; Bates, John T.; Loomis, Rebecca J.; Baneyx, Gretchen; Carrico, Chris; Jardine, Joseph G.; Rupert, Peter; Correnti, Colin; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Connell, Mary J.; Stevens, Eric; Schroeter, Alexandria; Chen, Man; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Holmes, Margaret A.; Li, Yuxing; Klevit, Rachel E.; Graham, Barney S.; Wyatt, Richard T.; Baker, David; Strong, Roland K.; Crowe, James E.; Johnson, Philip R.; Schief, William R.

2014-03-01

Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.

Identification of ultramodified proteins using top-down spectra

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiaowen; Hengel, Shawna M.; Wu, Si; Tolic, Nikola; Pasa-Tolic, Ljiljana; Pevzner, Pavel A.

2013-04-10

Post-translational modifications (PTMs) play an important role in various biological processes through changing protein structure and function. Some ultramodified proteins (like histones) have multiple PTMs forming PTM patterns that define the functionality of a protein. While bottom-up mass spectrometry (MS) has been successful in identifying individual PTMs within short peptides, it is unable to identify PTM patterns spread along entire proteins in a coordinated fashion. In contrast, top-down MS analyzes intact proteins and reveals PTM patterns along the entire proteins. However, while recent advances in instrumentation have made top-down MS accessible to many laboratories, most computational tools for top-down MS focus on proteins with few PTMs and are unable to identify complex PTM patterns. We propose a new algorithm, MS-Align-E, that identifies both expected and unexpected PTMs in ultramodified proteins. We demonstrate that MS-Align-E identifies many protein forms of histone H4 and benchmark it against the currently accepted software tools.

[Bioethics of principles].

Science.gov (United States)

Pérez-Soba Díez del Corral, Juan José

2008-01-01

Bioethics emerges about the tecnological problems of acting in human life. Emerges also the problem of the moral limits determination, because they seem exterior of this practice. The Bioethics of Principles, take his rationality of the teleological thinking, and the autonomism. These divergence manifest the epistemological fragility and the great difficulty of hmoralñ thinking. This is evident in the determination of autonomy's principle, it has not the ethical content of Kant's propose. We need a new ethic rationality with a new refelxion of new Principles whose emerges of the basic ethic experiences.

Principles of dynamics

CERN Document Server

Hill, Rodney

2013-01-01

Principles of Dynamics presents classical dynamics primarily as an exemplar of scientific theory and method. This book is divided into three major parts concerned with gravitational theory of planetary systems; general principles of the foundations of mechanics; and general motion of a rigid body. Some of the specific topics covered are Keplerian Laws of Planetary Motion; gravitational potential and potential energy; and fields of axisymmetric bodies. The principles of work and energy, fictitious body-forces, and inertial mass are also looked into. Other specific topics examined are kinematics

Principles for the formation of an effective concept of multifunctional high-rise construction investment projects

Directory of Open Access Journals (Sweden)

Beliakov Sergei

2018-01-01

Full Text Available Investment projects of high-rise construction have a number of features that determine specific risks and additional opportunities that require analysis and accounting in the formation of an effective project concept. The most significant features of high-rise construction include long construction time, complexity of technical and technological solutions, complexity of decisions on the organization of construction and operation, high cost of construction and operation, complexity in determining the ratio of areas designed to accommodate different functional areas, when organizing and coordinating the operation of the facility, with internal zoning. Taking into account the specificity of high-rise construction, among the factors determining the effectiveness of projects, it is advisable to consider as key factors: organizational, technological and investment factors. Within the framework of the article, the author singled out key particular functions for each group of factors under consideration, and also developed a system of principles for the formation of an effective concept of multifunctional high-rise construction investment projects, including the principle of logistic efficiency, the principle of optimal functional zoning, the principle of efficiency of equipment use, the principle of optimizing technological processes, the principle maximization of income, the principle of fund management, the principle of risk management . The model of formation of an effective concept of investment projects of multifunctional high-rise construction developed by the author can contribute to the development of methodological tools in the field of managing the implementation of high-rise construction projects, taking into account their specificity in the current economic conditions.

Principles for the formation of an effective concept of multifunctional high-rise construction investment projects

Science.gov (United States)

Beliakov, Sergei

2018-03-01

Investment projects of high-rise construction have a number of features that determine specific risks and additional opportunities that require analysis and accounting in the formation of an effective project concept. The most significant features of high-rise construction include long construction time, complexity of technical and technological solutions, complexity of decisions on the organization of construction and operation, high cost of construction and operation, complexity in determining the ratio of areas designed to accommodate different functional areas, when organizing and coordinating the operation of the facility, with internal zoning. Taking into account the specificity of high-rise construction, among the factors determining the effectiveness of projects, it is advisable to consider as key factors: organizational, technological and investment factors. Within the framework of the article, the author singled out key particular functions for each group of factors under consideration, and also developed a system of principles for the formation of an effective concept of multifunctional high-rise construction investment projects, including the principle of logistic efficiency, the principle of optimal functional zoning, the principle of efficiency of equipment use, the principle of optimizing technological processes, the principle maximization of income, the principle of fund management, the principle of risk management . The model of formation of an effective concept of investment projects of multifunctional high-rise construction developed by the author can contribute to the development of methodological tools in the field of managing the implementation of high-rise construction projects, taking into account their specificity in the current economic conditions.

Identification of novel direct protein-protein interactions by irradiating living cells with femtosecond UV laser pulses.

Science.gov (United States)

Itri, Francesco; Monti, Daria Maria; Chino, Marco; Vinciguerra, Roberto; Altucci, Carlo; Lombardi, Angela; Piccoli, Renata; Birolo, Leila; Arciello, Angela

2017-10-07

The identification of protein-protein interaction networks in living cells is becoming increasingly fundamental to elucidate main biological processes and to understand disease molecular bases on a system-wide level. We recently described a method (LUCK, Laser UV Cross-linKing) to cross-link interacting protein surfaces in living cells by UV laser irradiation. By using this innovative methodology, that does not require any protein modification or cell engineering, here we demonstrate that, upon UV laser irradiation of HeLa cells, a direct interaction between GAPDH and alpha-enolase was "frozen" by a cross-linking event. We validated the occurrence of this direct interaction by co-immunoprecipitation and Immuno-FRET analyses. This represents a proof of principle of the LUCK capability to reveal direct protein interactions in their physiological environment. Copyright © 2017 Elsevier Inc. All rights reserved.

An Embalse nuclear power plant basic principles simulator

International Nuclear Information System (INIS)

Fernandez, Oscar; Galdoz, Erwin; Flury, Celso; Fontanini, Horacio

1989-01-01

A nuclear power plant basic principles simulator is a package of programs that numerically solve the dynamic equations of the simulated plant. This kind of tools is mainly used in the first step of training of operational personnel, to allow mental representation of physical phenomena governing the plant. They are also used for students or professional training, and experienced operators can also improve there performance under abnormal operation situations using the simulator. For the Embalse nuclear power plant, mainly the thermohydraulic behaviour, is simulated. The mathematical model was adapted from MANUVR, a code developed at the Electric Systems and Control Department of the National Atomic Energy Commission (CNEA). (Author) [es

Using Technology for Ministry: Trends, Principles and Applications

Directory of Open Access Journals (Sweden)

Alfredo Vergel

2010-11-01

Full Text Available This survey of developments, guidelines and uses of technology by congregations and their leaders offers an overview of the topic and points to sources for further study. As technology plays a larger role in religious communities there is a need for guiding principles for its use. Congregational leaders do well to engage technology reflectively while staying informed on its possible applications in ministry. While this article is of primary interest to those in leadership positions at the congregational level, it can also serve both as a primer to seminary students and as a tool for librarians providing reference services on the topic.

32 CFR 776.19 - Principles.

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Principles. 776.19 Section 776.19 National... Professional Conduct § 776.19 Principles. The Rules of this subpart are based on the following principles... exists, this subpart should be interpreted consistent with these general principles. (a) Covered...

Environmental Decision Making on Acid Mine Drainage Issues in South Africa: An Argument for the Precautionary Principle.

Science.gov (United States)

Morodi, T J; Mpofu, Charles

2017-06-28

This paper examines the issue of acid mine drainage in South Africa and environmental decision making processes that could be taken to mitigate the problem in the context of both conventional risk assessment and the precautionary principle. It is argued that conventional risk assessment protects the status quo and hence cannot be entirely relied upon as an effective tool to resolve environmental problems in the context of South Africa, a developing country with complex environmental health concerns. The complexity of the environmental issues is discussed from historical and political perspectives. An argument is subsequently made that the precautionary principle is an alternative tool, and its adoption can be used to empower local communities. This work, therefore, adds to new knowledge by problematising conventional risk assessment and proposing the framing of the acid mine drainage issues in a complex and contextual scenario of a developing country-South Africa.

Integrating Ecosystem-Based Management Principles of Adaptive Management and Stakeholder Engagement in California Fisheries

Science.gov (United States)

Erickson, A.; Martone, R. G.; Hazen, L.; Mease, L.; Gourlie, D.; Le Cornu, E.; Ourens, R.; Micheli, F.

2016-12-01

California's fisheries management law, the Marine Life Management Act (MLMA) of 1998, signaled a transformative shift from traditional single-species management to an ecosystem-based approach. In response, the fisheries management community in California is striving to integrate new science and management innovations while maximizing its limited capacity. However, data gaps, high compliance costs, capacity constraints, and limited access to the best available data and technologies persist. Here we present two decision support tools being developed to aid California fisheries managers as they continue to implement ecosystem-based management (EBM). First, to practice adaptive management, a key principle of EBM, managers must know whether and how their decisions are meeting their management objectives over time. Based on a cross-walk of MLMA goals with metrics and indicators from sustainable fishery certification programs, we present a flexible and practical tool for tracking fishery management performance in California. We showcase a draft series of decision trees and questionnaires managers can use to quantitatively or qualitatively measure both ecological and social outcomes, helping them to prioritize management options and limited resources. Second, state fisheries managers acknowledge the need for more effective stakeholder engagement to facilitate and inform decision-making and long-term outcomes, another key principle of EBM. Here, we present a pilot version of a decision-support tool to aid managers in choosing the most appropriate stakeholder engagement strategies in various types of decision contexts. This online tool will help staff identify their engagement goals, when they can strategically engage stakeholders based on their needs, and the fishery characteristics that will inform how engagement strategies are tailored to specific contexts. We also share opportunities to expand these EBM tools to other resource management contexts and scales.

The Principle of General Tovariance

Science.gov (United States)

Heunen, C.; Landsman, N. P.; Spitters, B.

2008-06-01

We tentatively propose two guiding principles for the construction of theories of physics, which should be satisfied by a possible future theory of quantum gravity. These principles are inspired by those that led Einstein to his theory of general relativity, viz. his principle of general covariance and his equivalence principle, as well as by the two mysterious dogmas of Bohr's interpretation of quantum mechanics, i.e. his doctrine of classical concepts and his principle of complementarity. An appropriate mathematical language for combining these ideas is topos theory, a framework earlier proposed for physics by Isham and collaborators. Our principle of general tovariance states that any mathematical structure appearing in the laws of physics must be definable in an arbitrary topos (with natural numbers object) and must be preserved under so-called geometric morphisms. This principle identifies geometric logic as the mathematical language of physics and restricts the constructions and theorems to those valid in intuitionism: neither Aristotle's principle of the excluded third nor Zermelo's Axiom of Choice may be invoked. Subsequently, our equivalence principle states that any algebra of observables (initially defined in the topos Sets) is empirically equivalent to a commutative one in some other topos.