A promising future for integrative biodiversity research: an increased role of scale-dependency and functional biology

Science.gov (United States)

Schmitz, L.

2016-01-01

Studies into the complex interaction between an organism and changes to its biotic and abiotic environment are fundamental to understanding what regulates biodiversity. These investigations occur at many phylogenetic, temporal and spatial scales and within a variety of biological and geological disciplines but often in relative isolation. This issue focuses on what can be achieved when ecological mechanisms are integrated into analyses of deep-time biodiversity patterns through the union of fossil and extant data and methods. We expand upon this perspective to argue that, given its direct relevance to the current biodiversity crisis, greater integration is needed across biodiversity research. We focus on the need to understand scaling effects, how lower-level ecological and evolutionary processes scale up and vice versa, and the importance of incorporating functional biology. Placing function at the core of biodiversity research is fundamental, as it establishes how an organism interacts with its abiotic and biotic environment and it is functional diversity that ultimately determines important ecosystem processes. To achieve full integration, concerted and ongoing efforts are needed to build a united and interactive community of biodiversity researchers, with education and interdisciplinary training at its heart. PMID:26977068

A promising future for integrative biodiversity research: an increased role of scale-dependency and functional biology.

Science.gov (United States)

Price, S A; Schmitz, L

2016-04-05

Studies into the complex interaction between an organism and changes to its biotic and abiotic environment are fundamental to understanding what regulates biodiversity. These investigations occur at many phylogenetic, temporal and spatial scales and within a variety of biological and geological disciplines but often in relative isolation. This issue focuses on what can be achieved when ecological mechanisms are integrated into analyses of deep-time biodiversity patterns through the union of fossil and extant data and methods. We expand upon this perspective to argue that, given its direct relevance to the current biodiversity crisis, greater integration is needed across biodiversity research. We focus on the need to understand scaling effects, how lower-level ecological and evolutionary processes scale up and vice versa, and the importance of incorporating functional biology. Placing function at the core of biodiversity research is fundamental, as it establishes how an organism interacts with its abiotic and biotic environment and it is functional diversity that ultimately determines important ecosystem processes. To achieve full integration, concerted and ongoing efforts are needed to build a united and interactive community of biodiversity researchers, with education and interdisciplinary training at its heart. © 2016 The Author(s).

Functional diversification of Argonautes in nematodes: an expanding universe.

Science.gov (United States)

Buck, Amy H; Blaxter, Mark

2013-08-01

In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism.

Distinguishing between "function" and "effect" in genome biology.

Science.gov (United States)

Doolittle, W Ford; Brunet, Tyler D P; Linquist, Stefan; Gregory, T Ryan

2014-05-09

Much confusion in genome biology results from conflation of possible meanings of the word "function." We suggest that, in this connection, attention should be paid to evolutionary biologists and philosophers who have previously dealt with this problem. We need only decide that although all genomic structures have effects, only some of them should be said to have functions. Although it will very often be difficult or impossible to establish function (strictly defined), it should not automatically be assumed. We enjoin genomicists in particular to pay greater attention to parsing biological effects. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

A Unifying Theory of Biological Function

NARCIS (Netherlands)

van Hateren, J. H.

2017-01-01

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological (or selected effects) theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms

A functional overview of conservation biological control

DEFF Research Database (Denmark)

Begg, Graham S; Cook, Samantha M; Dye, Richard

2017-01-01

Conservation biological control (CBC) is a sustainable approach to pest management that can contribute to a reduction in pesticide use as part of an Integrated Pest Management (IPM) strategy. CBC is based on the premise that countering habitat loss and environmental disturbance associated...... CBC prescriptions have proved elusive. To tackle this, we consolidate existing knowledge of CBC using a simple conceptual model that organises the functional elements of CBC into a common, unifying framework. We identify and integrate the key biological processes affecting natural enemies...... and their biological control function across local and regional scales, and consider the interactions, interdependencies and constraints that determine the outcome of CBC strategies. Conservation measures are often effective in supporting natural enemy populations but their success cannot be guaranteed; the greatest...

The diverse and expanding role of mass spectrometry in structural and molecular biology.

Science.gov (United States)

Lössl, Philip; van de Waterbeemd, Michiel; Heck, Albert Jr

2016-12-15

The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-deuterium exchange-MS, nowadays enable the characterization of biomolecular structures, functions, and interactions. In particular, we focus on the role of mass spectrometry in integrated structural and molecular biology investigations of biological macromolecular complexes and cellular machineries, highlighting work on CRISPR-Cas systems and eukaryotic transcription complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Uncovering Biological Network Function via Graphlet Degree Signatures

Directory of Open Access Journals (Sweden)

Nataša Pržulj

2008-01-01

Full Text Available Motivation: Proteins are essential macromolecules of life and thus understanding their function is of great importance. The number of functionally unclassified proteins is large even for simple and well studied organisms such as baker’s yeast. Methods for determining protein function have shifted their focus from targeting specific proteins based solely on sequence homology to analyses of the entire proteome based on protein-protein interaction (PPI networks. Since proteins interact to perform a certain function, analyzing structural properties of PPI networks may provide useful clues about the biological function of individual proteins, protein complexes they participate in, and even larger subcellular machines.Results: We design a sensitive graph theoretic method for comparing local structures of node neighborhoods that demonstrates that in PPI networks, biological function of a node and its local network structure are closely related. The method summarizes a protein’s local topology in a PPI network into the vector of graphlet degrees called the signature of the protein and computes the signature similarities between all protein pairs. We group topologically similar proteins under this measure in a PPI network and show that these protein groups belong to the same protein complexes, perform the same biological functions, are localized in the same subcellular compartments, and have the same tissue expressions. Moreover, we apply our technique on a proteome-scale network data and infer biological function of yet unclassified proteins demonstrating that our method can provide valuable guidelines for future experimental research such as disease protein prediction.Availability: Data is available upon request.

Synthetic Biology Open Language Visual (SBOL Visual) Version 2.0

KAUST Repository

Cox, Robert Sidney

2018-03-24

People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.0 of SBOL Visual, which builds on the prior SBOL Visual 1.0 standard by expanding diagram syntax to include functional interactions and molecular species, making the relationship between diagrams and the SBOL data model explicit, supporting families of symbol variants, clarifying a number of requirements and best practices, and significantly expanding the collection of diagram glyphs.

Towards Integration of Biological and Physiological Functions at Multiple Levels

Directory of Open Access Journals (Sweden)

Taishin eNomura

2010-12-01

Full Text Available An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowledge of biological and physiological functions at multiple levels of time and space with the use of information technology infrastructure. Emphasis will be made for systematic, modular, hierarchical, and standardized descriptions of mathematical models of the functions and advantages for the use of them.

Function of dynamic models in systems biology: linking structure to behaviour.

Science.gov (United States)

Knüpfer, Christian; Beckstein, Clemens

2013-10-08

Dynamic models in Systems Biology are used in computational simulation experiments for addressing biological questions. The complexity of the modelled biological systems and the growing number and size of the models calls for computer support for modelling and simulation in Systems Biology. This computer support has to be based on formal representations of relevant knowledge fragments. In this paper we describe different functional aspects of dynamic models. This description is conceptually embedded in our "meaning facets" framework which systematises the interpretation of dynamic models in structural, functional and behavioural facets. Here we focus on how function links the structure and the behaviour of a model. Models play a specific role (teleological function) in the scientific process of finding explanations for dynamic phenomena. In order to fulfil this role a model has to be used in simulation experiments (pragmatical function). A simulation experiment always refers to a specific situation and a state of the model and the modelled system (conditional function). We claim that the function of dynamic models refers to both the simulation experiment executed by software (intrinsic function) and the biological experiment which produces the phenomena under investigation (extrinsic function). We use the presented conceptual framework for the function of dynamic models to review formal accounts for functional aspects of models in Systems Biology, such as checklists, ontologies, and formal languages. Furthermore, we identify missing formal accounts for some of the functional aspects. In order to fill one of these gaps we propose an ontology for the teleological function of models. We have thoroughly analysed the role and use of models in Systems Biology. The resulting conceptual framework for the function of models is an important first step towards a comprehensive formal representation of the functional knowledge involved in the modelling and simulation process

Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

Directory of Open Access Journals (Sweden)

Ye-Rang Yun

2010-01-01

Full Text Available Fibroblast growth factors (FGFs that signal through FGF receptors (FGFRs regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

The biological function of consciousness

Directory of Open Access Journals (Sweden)

Brian eEarl

2014-08-01

Full Text Available This research is an investigation of whether consciousness—one’s ongoing experience—influences one’s behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1 contrary to one’s intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2 consciousness does have a biological function; and (3 consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc., is incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness.

The expanding universe of noncoding RNAs.

Science.gov (United States)

Hannon, G J; Rivas, F V; Murchison, E P; Steitz, J A

2006-01-01

The 71st Cold Spring Harbor Symposium on Quantitative Biology celebrated the numerous and expanding roles of regulatory RNAs in systems ranging from bacteria to mammals. It was clearly evident that noncoding RNAs are undergoing a renaissance, with reports of their involvement in nearly every cellular process. Previously known classes of longer noncoding RNAs were shown to function by every possible means-acting catalytically, sensing physiological states through adoption of complex secondary and tertiary structures, or using their primary sequences for recognition of target sites. The many recently discovered classes of small noncoding RNAs, generally less than 35 nucleotides in length, most often exert their effects by guiding regulatory complexes to targets via base-pairing. With the ability to analyze the RNA products of the genome in ever greater depth, it has become clear that the universe of noncoding RNAs may extend far beyond the boundaries we had previously imagined. Thus, as much as the Symposium highlighted exciting progress in the field, it also revealed how much farther we must go to understand fully the biological impact of noncoding RNAs.

The expanding regulatory universe of p53 in gastrointestinal cancer [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Andrew Fesler

2016-04-01

Full Text Available Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs. Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

Expand Your Horizon: A programme that improves body image and reduces self-objectification by training women to focus on body functionality.

Science.gov (United States)

Alleva, Jessica M; Martijn, Carolien; Van Breukelen, Gerard J P; Jansen, Anita; Karos, Kai

2015-09-01

This study tested Expand Your Horizon, a programme designed to improve body image by training women to focus on the functionality of their body using structured writing assignments. Eighty-one women (Mage=22.77) with a negative body image were randomised to the Expand Your Horizon programme or to an active control programme. Appearance satisfaction, functionality satisfaction, body appreciation, and self-objectification were measured at pretest, posttest, and one-week follow-up. Following the intervention, participants in the Expand Your Horizon programme experienced greater appearance satisfaction, functionality satisfaction, and body appreciation, and lower levels of self-objectification, compared to participants in the control programme. Partial eta-squared effect sizes were of small to medium magnitude. This study is the first to show that focusing on body functionality can improve body image and reduce self-objectification in women with a negative body image. These findings provide support for addressing body functionality in programmes designed to improve body image. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expanding the landscape of chromatin modification (CM-related functional domains and genes in human.

Directory of Open Access Journals (Sweden)

Shuye Pu

2010-11-01

Full Text Available Chromatin modification (CM plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available.

Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

Science.gov (United States)

Li, Jun; Zhao, Patrick X

2016-01-01

Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/.

Expanded explorations into the optimization of an energy function for protein design

Science.gov (United States)

Huang, Yao-ming; Bystroff, Christopher

2014-01-01

Nature possesses a secret formula for the energy as a function of the structure of a protein. In protein design, approximations are made to both the structural representation of the molecule and to the form of the energy equation, such that the existence of a general energy function for proteins is by no means guaranteed. Here we present new insights towards the application of machine learning to the problem of finding a general energy function for protein design. Machine learning requires the definition of an objective function, which carries with it the implied definition of success in protein design. We explored four functions, consisting of two functional forms, each with two criteria for success. Optimization was carried out by a Monte Carlo search through the space of all variable parameters. Cross-validation of the optimized energy function against a test set gave significantly different results depending on the choice of objective function, pointing to relative correctness of the built-in assumptions. Novel energy cross-terms correct for the observed non-additivity of energy terms and an imbalance in the distribution of predicted amino acids. This paper expands on the work presented at ACM-BCB, Orlando FL , October 2012. PMID:24384706

Physical, chemical, and metabolic state sensors expand the synthetic biology toolbox for Synechocystis sp. PCC 6803.

Science.gov (United States)

Immethun, Cheryl M; DeLorenzo, Drew M; Focht, Caroline M; Gupta, Dinesh; Johnson, Charles B; Moon, Tae Seok

2017-07-01

Many under-developed organisms possess important traits that can boost the effectiveness and sustainability of microbial biotechnology. Photoautotrophic cyanobacteria can utilize the energy captured from light to fix carbon dioxide for their metabolic needs while living in environments not suited for growing crops. Various value-added compounds have been produced by cyanobacteria in the laboratory; yet, the products' titers and yields are often not industrially relevant and lag behind what have been accomplished in heterotrophic microbes. Genetic tools for biological process control are needed to take advantage of cyanobacteria's beneficial qualities, as tool development also lags behind what has been created in common heterotrophic hosts. To address this problem, we developed a suite of sensors that regulate transcription in the model cyanobacterium Synechocystis sp. PCC 6803 in response to metabolically relevant signals, including light and the cell's nitrogen status, and a family of sensors that respond to the inexpensive chemical, l-arabinose. Increasing the number of available tools enables more complex and precise control of gene expression. Expanding the synthetic biology toolbox for this cyanobacterium also improves our ability to utilize this important under-developed organism in biotechnology. Biotechnol. Bioeng. 2017;114: 1561-1569. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Lipid polymorphism and the functional roles of lipids in biological membranes

NARCIS (Netherlands)

Cullis, P.R.; Kruijff, B. de

1979-01-01

The reasons for the great variety of lipids found in biological membranes, and the relations between lipid composition and membrane function pose major unsolved problems in membrane biology. Perhaps the only major functional role of lipids which may be regarded as firmly established involves the

Functional biology of sympatric krill species

DEFF Research Database (Denmark)

Agersted, Mette Dalgaard; Nielsen, Torkel Gissel

2016-01-01

Here we compare the functional biology of the sympatric krill species, Meganyctiphanes norvegica and Thysanoessa inermis. For M. norvegica, we investigated functional responses on diatoms and copepods, together with prey size spectra on plankton ,400 mm and copepods in the size range 500–3220 mm....... For T. inermis, only prey size spectrum on plankton ,400 mm were investigated. The prey size ranges of both species include organisms ,400 mm, and they consequently graze on several trophic levels. However, T. inermis feed on cells ,10 mm equivalent spherical diameter (ESD), whereas M. norvegica only...

The reflection of life functional entailment and imminence in relational biology

CERN Document Server

Louie, A H

2013-01-01

A. H. Louie’s The Reflection of Life: Functional Entailment and Imminence in Relational Biology is a continuation of the exploratory journey in relational biology which began with his 2009 monograph More Than Life Itself: A Synthetic Continuation in Relational Biology. The theme of his first book was ‘What is life?’; the theme of this sequel is “How do two life forms interact?” Biology is a subject concerned with organization of relations. Relational biology is the approach that advocates ‘function dictates structure”, rather than ‘structure implies function’. It is mathematics decoded into biological realizations. The book demonstrates some of the powers of the approach of relational biology, and illustrates how pertinent problems in biology can be better addressed this way. In the first volume the theory was developed by using partially ordered sets, lattices, simulations, models, Aristotle’s four causes, graphs, categories, simple and complex systems, anticipatory systems, and metabolis...

Synthetic Biology and Personalized Medicine

Science.gov (United States)

Jain, K.K.

2013-01-01

Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

Expanding Pseudorandom Functions

DEFF Research Database (Denmark)

Damgård, Ivan Bjerre; Nielsen, Jesper Buus

2002-01-01

Given any weak pseudorandom function, we present a general and efficient technique transforming such a function to a new weak pseudorandom function with an arbitrary length output. This implies, among other things, an encryption mode for block ciphers. The mode is as efficient as known (and widely...... used) encryption modes as CBC mode and counter (CTR) mode, but is provably secure against chosen-plaintext attack (CPA) already if the underlying symmetric cipher is secure against known-plaintext attack (KPA). We prove that CBC, CTR and Jutla’s integrity aware modes do not have this property....... In particular, we prove that when using a KPA secure block cipher, then: CBC mode is KPA secure, but need not be CPA secure, Jutla’s modes need not be CPA secure, and CTR mode need not be even KPA secure. The analysis is done in a concrete security framework....

The correlation function for density perturbations in an expanding universe. IV - The evolution of the correlation function. [galaxy distribution

Science.gov (United States)

Mcclelland, J.; Silk, J.

1979-01-01

The evolution of the two-point correlation function for the large-scale distribution of galaxies in an expanding universe is studied on the assumption that the perturbation densities lie in a Gaussian distribution centered on any given mass scale. The perturbations are evolved according to the Friedmann equation, and the correlation function for the resulting distribution of perturbations at the present epoch is calculated. It is found that: (1) the computed correlation function gives a satisfactory fit to the observed function in cosmological models with a density parameter (Omega) of approximately unity, provided that a certain free parameter is suitably adjusted; (2) the power-law slope in the nonlinear regime reflects the initial fluctuation spectrum, provided that the density profile of individual perturbations declines more rapidly than the -2.4 power of distance; and (3) both positive and negative contributions to the correlation function are predicted for cosmological models with Omega less than unity.

Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.

Directory of Open Access Journals (Sweden)

Christopher Y Park

Full Text Available A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods (e.g. BLAST have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer (FKT dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11,000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics

Telomere biology in aging and cancer: early history and perspectives.

Science.gov (United States)

Hayashi, Makoto T

2018-01-20

The ends of eukaryotic linear chromosomes are protected from undesired enzymatic activities by a nucleoprotein complex called the telomere. Expanding evidence indicates that telomeres have central functions in human aging and tumorigenesis. While it is undoubtedly important to follow current advances in telomere biology, it is also fruitful to be well informed in seminal historical studies for a comprehensive understanding of telomere biology, and for the anticipation of future directions. With this in mind, I here summarize the early history of telomere biology and current advances in the field, mostly focusing on mammalian studies relevant to aging and cancer.

Enhancing microbial production of biofuels by expanding microbial metabolic pathways.

Science.gov (United States)

Yu, Ping; Chen, Xingge; Li, Peng

2017-09-01

Fatty acid, isoprenoid, and alcohol pathways have been successfully engineered to produce biofuels. By introducing three genes, atfA, adhE, and pdc, into Escherichia coli to expand fatty acid pathway, up to 1.28 g/L of fatty acid ethyl esters can be achieved. The isoprenoid pathway can be expanded to produce bisabolene with a high titer of 900 mg/L in Saccharomyces cerevisiae. Short- and long-chain alcohols can also be effectively biosynthesized by extending the carbon chain of ketoacids with an engineered "+1" alcohol pathway. Thus, it can be concluded that expanding microbial metabolic pathways has enormous potential for enhancing microbial production of biofuels for future industrial applications. However, some major challenges for microbial production of biofuels should be overcome to compete with traditional fossil fuels: lowering production costs, reducing the time required to construct genetic elements and to increase their predictability and reliability, and creating reusable parts with useful and predictable behavior. To address these challenges, several aspects should be further considered in future: mining and transformation of genetic elements related to metabolic pathways, assembling biofuel elements and coordinating their functions, enhancing the tolerance of host cells to biofuels, and creating modular subpathways that can be easily interconnected. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Mammalian synthetic biology for studying the cell.

Science.gov (United States)

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

Milk protein tailoring to improve functional and biological properties

Directory of Open Access Journals (Sweden)

JEAN-MARC CHOBERT

2012-01-01

Full Text Available Proteins are involved in every aspects of life: structure, motion, catalysis, recognition and regulation. Today's highly sophisticated science of the modifications of proteins has ancient roots. The tailoring of proteins for food and medical uses precedes the beginning of what is called biochemistry. Chemical modification of proteins was pursued early in the twentieth century as an analytical procedure for side-chain amino acids. Later, methods were developed for specific inactivation of biologically active proteins and titration of their essential groups. Enzymatic modifications were mainly developed in the seventies when many more enzymes became economically available. Protein engineering has become a valuable tool for creating or improving proteins for practical use and has provided new insights into protein structure and function. The actual and potential use of milk proteins as food ingredients has been a popular topic for research over the past 40 years. With today's sophisticated analytical, biochemical and biological research tools, the presence of compounds with biological activity has been demonstrated. Improvements in separation techniques and enzyme technology have enabled efficient and economic isolation and modification of milk proteins, which has made possible their use as functional foods, dietary supplements, nutraceuticals and medical foods. In this review, some chemical and enzymatic modifications of milk proteins are described, with particular focus on their functional and biological properties.

Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.

Science.gov (United States)

Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko

2013-05-01

In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.

Biological pathways and genetic mechanisms involved in social functioning.

Science.gov (United States)

Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

2013-08-01

To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

Biologic variability and correlation of platelet function testing in healthy dogs.

Science.gov (United States)

Blois, Shauna L; Lang, Sean T; Wood, R Darren; Monteith, Gabrielle

2015-12-01

Platelet function tests are influenced by biologic variability, including inter-individual (CVG ) and intra-individual (CVI ), as well as analytic (CVA ) variability. Variability in canine platelet function testing is unknown, but if excessive, would make it difficult to interpret serial results. Additionally, the correlation between platelet function tests is poor in people, but not well described in dogs. The aims were to: (1) identify the effect of variation in preanalytic factors (venipuncture, elapsed time until analysis) on platelet function tests; (2) calculate analytic and biologic variability of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced thromboelastograph platelet mapping (TEG-PM), ADP-, AA-, and collagen-induced whole blood platelet aggregometry (WBA), and collagen/ADP and collagen/epinephrine platelet function analysis (PFA-CADP, PFA-CEPI); and (3) determine the correlation between these variables. In this prospective observational trial, platelet function was measured once every 7 days, for 4 consecutive weeks, in 9 healthy dogs. In addition, CBC, TEG-PM, WBA, and PFA were performed. Overall coefficients of variability ranged from 13.3% to 87.8% for the platelet function tests. Biologic variability was highest for AA-induced maximum amplitude generated during TEG-PM (MAAA; CVG = 95.3%, CVI = 60.8%). Use of population-based reference intervals (RI) was determined appropriate only for PFA-CADP (index of individuality = 10.7). There was poor correlation between most platelet function tests. Use of population-based RI appears inappropriate for most platelet function tests, and tests poorly correlate with one another. Future studies on biologic variability and correlation of platelet function tests should be performed in dogs with platelet dysfunction and those treated with antiplatelet therapy. © 2015 American Society for Veterinary Clinical Pathology.

Function and regulation of lipid biology in Caenorhabditis elegans aging

Directory of Open Access Journals (Sweden)

Nicole Shangming Hou

2012-05-01

Full Text Available Rapidly expanding aging populations and a concomitant increase in the prevalence of age-related diseases are global health problems today. Over the past three decades, a large body of work has led to the identification of genes and regulatory networks that affect longevity and health span, often benefitting from the tremendous power of genetics in vertebrate and invertebrate model organisms. Interestingly, many of these factors appear linked to lipids, important molecules that participate in cellular signaling, energy metabolism, and structural compartmentalization. Despite the putative link between lipids and longevity, the role of lipids in aging remains poorly understood. Emerging data from the model organism Caenorhabditis elegans suggest that lipid composition may change during aging, as several pathways that influence aging also regulate lipid metabolism enzymes; moreover, some of these enzymes apparently play key roles in the pathways that affect the rate of aging. By understanding how lipid biology is regulated during C. elegans aging, and how it impacts molecular, cellular and organismal function, we may gain insight into novel ways to delay aging using genetic or pharmacological interventions. In the present review we discuss recent insights into the roles of lipids in C. elegans aging, including regulatory roles played by lipids themselves, the regulation of lipid metabolic enzymes, and the roles of lipid metabolism genes in the pathways that affect aging.

Functional evolution of new and expanded attention networks in humans.

Science.gov (United States)

Patel, Gaurav H; Yang, Danica; Jamerson, Emery C; Snyder, Lawrence H; Corbetta, Maurizio; Ferrera, Vincent P

2015-07-28

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.

Dynamic Biological Functioning Important for Simulating and Stabilizing Ocean Biogeochemistry

Science.gov (United States)

Buchanan, P. J.; Matear, R. J.; Chase, Z.; Phipps, S. J.; Bindoff, N. L.

2018-04-01

The biogeochemistry of the ocean exerts a strong influence on the climate by modulating atmospheric greenhouse gases. In turn, ocean biogeochemistry depends on numerous physical and biological processes that change over space and time. Accurately simulating these processes is fundamental for accurately simulating the ocean's role within the climate. However, our simulation of these processes is often simplistic, despite a growing understanding of underlying biological dynamics. Here we explore how new parameterizations of biological processes affect simulated biogeochemical properties in a global ocean model. We combine 6 different physical realizations with 6 different biogeochemical parameterizations (36 unique ocean states). The biogeochemical parameterizations, all previously published, aim to more accurately represent the response of ocean biology to changing physical conditions. We make three major findings. First, oxygen, carbon, alkalinity, and phosphate fields are more sensitive to changes in the ocean's physical state. Only nitrate is more sensitive to changes in biological processes, and we suggest that assessment protocols for ocean biogeochemical models formally include the marine nitrogen cycle to assess their performance. Second, we show that dynamic variations in the production, remineralization, and stoichiometry of organic matter in response to changing environmental conditions benefit the simulation of ocean biogeochemistry. Third, dynamic biological functioning reduces the sensitivity of biogeochemical properties to physical change. Carbon and nitrogen inventories were 50% and 20% less sensitive to physical changes, respectively, in simulations that incorporated dynamic biological functioning. These results highlight the importance of a dynamic biology for ocean properties and climate.

Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

Science.gov (United States)

Kinjo, Akira R.; Nakamura, Haruki

2012-01-01

Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

Linking structural features of protein complexes and biological function.

Science.gov (United States)

Sowmya, Gopichandran; Breen, Edmond J; Ranganathan, Shoba

2015-09-01

Protein-protein interaction (PPI) establishes the central basis for complex cellular networks in a biological cell. Association of proteins with other proteins occurs at varying affinities, yet with a high degree of specificity. PPIs lead to diverse functionality such as catalysis, regulation, signaling, immunity, and inhibition, playing a crucial role in functional genomics. The molecular principle of such interactions is often elusive in nature. Therefore, a comprehensive analysis of known protein complexes from the Protein Data Bank (PDB) is essential for the characterization of structural interface features to determine structure-function relationship. Thus, we analyzed a nonredundant dataset of 278 heterodimer protein complexes, categorized into major functional classes, for distinguishing features. Interestingly, our analysis has identified five key features (interface area, interface polar residue abundance, hydrogen bonds, solvation free energy gain from interface formation, and binding energy) that are discriminatory among the functional classes using Kruskal-Wallis rank sum test. Significant correlations between these PPI interface features amongst functional categories are also documented. Salt bridges correlate with interface area in regulator-inhibitors (r = 0.75). These representative features have implications for the prediction of potential function of novel protein complexes. The results provide molecular insights for better understanding of PPIs and their relation to biological functions. © 2015 The Protein Society.

Developments in the Tools and Methodologies of Synthetic Biology

Science.gov (United States)

Kelwick, Richard; MacDonald, James T.; Webb, Alexander J.; Freemont, Paul

2014-01-01

Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices, or systems. However, biological systems are generally complex and unpredictable, and are therefore, intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a “body of knowledge” from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled, and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled, and its functionality tested. At each stage of the design cycle, an expanding repertoire of tools is being developed. In this review, we highlight several of these tools in terms of their applications and benefits to the synthetic biology community. PMID:25505788

Developments in the tools and methodologies of synthetic biology

Directory of Open Access Journals (Sweden)

Richard eKelwick

2014-11-01

Full Text Available Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices or systems. However, biological systems are generally complex and unpredictable and are therefore intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a ‘body of knowledge’ from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled and its functionality tested. At each stage of the design cycle an expanding repertoire of tools is being developed. In this review we highlight several of these tools in terms of their applications and benefits to the synthetic biology community.

Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype.

Science.gov (United States)

Koenighofer, M; Hung, C Y; McCauley, J L; Dallman, J; Back, E J; Mihalek, I; Gripp, K W; Sol-Church, K; Rusconi, P; Zhang, Z; Shi, G-X; Andres, D A; Bodamer, O A

2016-03-01

RASopathies are a clinically heterogeneous group of conditions caused by mutations in 1 of 16 proteins in the RAS-mitogen activated protein kinase (RAS-MAPK) pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins; however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Structure-based function prediction of the expanding mollusk tyrosinase family

Science.gov (United States)

Huang, Ronglian; Li, Li; Zhang, Guofan

2017-11-01

Tyrosinase (Ty) is a common enzyme found in many different animal groups. In our previous study, genome sequencing revealed that the Ty family is expanded in the Pacific oyster ( Crassostrea gigas). Here, we examine the larger number of Ty family members in the Pacific oyster by high-level structure prediction to obtain more information about their function and evolution, especially the unknown role in biomineralization. We verified 12 Ty gene sequences from Crassostrea gigas genome and Pinctada fucata martensii transcriptome. By using phylogenetic analysis of these Tys with functionally known Tys from other molluscan species, eight subgroups were identified (CgTy_s1, CgTy_s2, MolTy_s1, MolTy-s2, MolTy-s3, PinTy-s1, PinTy-s2 and PviTy). Structural data and surface pockets of the dinuclear copper center in the eight subgroups of molluscan Ty were obtained using the latest versions of prediction online servers. Structural comparison with other Ty proteins from the protein databank revealed functionally important residues (HA1, HA2, HA3, HB1, HB2, HB3, Z1-Z9) and their location within these protein structures. The structural and chemical features of these pockets which may related to the substrate binding showed considerable variability among mollusks, which undoubtedly defines Ty substrate binding. Finally, we discuss the potential driving forces of Ty family evolution in mollusks. Based on these observations, we conclude that the Ty family has rapidly evolved as a consequence of substrate adaptation in mollusks.

Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.

Directory of Open Access Journals (Sweden)

Weiting Du

Full Text Available Foxp3(+ regulatory T cells (Treg play a crucial role in regulating immune tolerance. The use of Treg to restore immune tolerance is considered an attractive novel approach to inhibit autoimmune disease, including type 1 diabetes (T1D, and to prevent rejection of organ transplants. In view of the goal of developing autologous Treg-based cell therapy for patients with long-term (>15 years T1D, it will be necessary to expand a sufficient amount of functional Treg in vitro in order to study and compare Treg from T1D patients and healthy subjects. Our results have demonstrated that there is a comparable frequency of Treg in the peripheral blood lymphocytes (PBLs of patients with long-term T1D relative to those in healthy subjects; however, Th1 cells, but not Th17 cells, were increased in the T1D patients. Further, more Treg in PBLs from T1D patients than from healthy subjects expressed the CD45RO(+ memory cell phenotype, suggesting they were antigen-experienced cells. After isolation, Treg from both T1D patients and healthy subjects were successfully expanded with high purity. Although there was no difference in Helios expression on Treg in PBLs, in vitro expansion led to fewer Helios-expressing Treg from T1D patients than healthy subjects. While more Th1-like Treg expressing IFN-γ or TNF-α were found in the PBLs of T1D patients than healthy controls, there was no such difference in the expanded Treg. Importantly, expanded Treg from both subject groups were able to suppress autologous or allogeneic CD8(+ effector T cells equally well. Our findings demonstrate that a large number of ex vivo expanded functional Treg can be obtained from long-term T1D patients, although fewer expanded Treg expressed a high level of Helios. Thus, based on the positive outcomes, these potent expanded Treg from diabetic human patients may be useful in treating T1D or preventing islet graft rejection.

SU-E-T-54: Benefits of Biological Cost Functions

International Nuclear Information System (INIS)

Demirag, N

2014-01-01

Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 and 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics

Systems Biology and Health Systems Complexity in;

NARCIS (Netherlands)

Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.

2016-01-01

Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

2011 Archaea: Ecology, Metabolism, & Molecular Biology

Energy Technology Data Exchange (ETDEWEB)

Keneth Stedman

2011-08-05

Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

Design of the Nonlinear Pin Rubber Forming Equipment Integrating the Functions of Extruding, Dewatering, Drying & Expanding

Directory of Open Access Journals (Sweden)

Yuefeng Yuan

2014-12-01

Full Text Available The top priority of car-tire suppliers is to improve wetland grip force of the using tires, reduce the rolling resistance and the rolling noise of tires. It is urgent for the tire industry to research and develop high-performance tires to solve the above problems. They must use the high- performance synthetic rubber and auxiliary rubber to develop the most advanced manufacturing technologies and equipment. Silica, a kind of important tire auxiliary rubber, can significantly reduce the rolling resistance of tires, improve the grip force and properties resistant to ice, wetness or slippery of tires. In this paper, based on the conventional tire rubber forming technologies of extrusion, dewatering, drying and expanding, a study is made on the conical screw, the dewatering barrel, the drying barrel, the pin layout scheme, the expanding die head, cutter and the control system. The nonlinear pin rubber forming equipment integrating the functions of extrusion, dewatering, drying and expanding is designed and applied to tire auxiliary rubber forming. The experiment shows that the forming device can realize the one-step forming, with high forming efficiency, low cost and less labor.

Expanding beyond canonical metabolism: Interfacing alternative elements, synthetic biology, and metabolic engineering

Directory of Open Access Journals (Sweden)

Kevin B. Reed

2018-03-01

Full Text Available Metabolic engineering offers an exquisite capacity to produce new molecules in a renewable manner. However, most industrial applications have focused on only a small subset of elements from the periodic table, centered around carbon biochemistry. This review aims to illustrate the expanse of chemical elements that can currently (and potentially be integrated into useful products using cellular systems. Specifically, we describe recent advances in expanding the cellular scope to include the halogens, selenium and the metalloids, and a variety of metal incorporations. These examples range from small molecules, heteroatom-linked uncommon elements, and natural products to biomining and nanotechnology applications. Collectively, this review covers the promise of an expanded range of elemental incorporations and the future impacts it may have on biotechnology.

Evolutionary cell biology: functional insight from "endless forms most beautiful".

Science.gov (United States)

Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

2015-12-15

In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. © 2015 Richardson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Chemically-functionalized microcantilevers for detection of chemical, biological and explosive material

Science.gov (United States)

Pinnaduwage, Lal A [Knoxville, TN; Thundat, Thomas G [Knoxville, TN; Brown, Gilbert M [Knoxville, TN; Hawk, John Eric [Olive Branch, MS; Boiadjiev, Vassil I [Knoxville, TN

2007-04-24

A chemically functionalized cantilever system has a cantilever coated on one side thereof with a reagent or biological species which binds to an analyte. The system is of particular value when the analyte is a toxic chemical biological warfare agent or an explosive.

Heavy water effects on the structure, functions and behavior of biological systems

International Nuclear Information System (INIS)

Buzgariu, Wanda; Caloianu, Maria; Moldovan, Lucia; Titescu, G.

2003-01-01

The H 2 O substitution for D 2 O either in environment or in the culture medium of the living systems generates changes in their main functions and composition. In this paper some of the heavy water effects in biological systems such as structural and functional changes were reviewed: normal cell architecture alterations, cell division and membrane functions disturbance, muscular contractility and the perturbations of biological oscillators such as circadian rhythm, heart rate, respiratory cycle, tidal and ultradian rhythm. (authors)

Sharing Structure and Function in Biological Design with SBOL 2.0.

Science.gov (United States)

Roehner, Nicholas; Beal, Jacob; Clancy, Kevin; Bartley, Bryan; Misirli, Goksel; Grünberg, Raik; Oberortner, Ernst; Pocock, Matthew; Bissell, Michael; Madsen, Curtis; Nguyen, Tramy; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Densmore, Douglas; Gennari, John H; Wipat, Anil; Sauro, Herbert M; Myers, Chris J

2016-06-17

The Synthetic Biology Open Language (SBOL) is a standard that enables collaborative engineering of biological systems across different institutions and tools. SBOL is developed through careful consideration of recent synthetic biology trends, real use cases, and consensus among leading researchers in the field and members of commercial biotechnology enterprises. We demonstrate and discuss how a set of SBOL-enabled software tools can form an integrated, cross-organizational workflow to recapitulate the design of one of the largest published genetic circuits to date, a 4-input AND sensor. This design encompasses the structural components of the system, such as its DNA, RNA, small molecules, and proteins, as well as the interactions between these components that determine the system's behavior/function. The demonstrated workflow and resulting circuit design illustrate the utility of SBOL 2.0 in automating the exchange of structural and functional specifications for genetic parts, devices, and the biological systems in which they operate.

[Cycloferon biological activity characteristics].

Science.gov (United States)

Utkina, T M; Potekhina, L P; Kartashova, O L; Vasilchenko, A S

2014-01-01

Study the effect of cycloferon in experimental and clinical conditions on persistence properties of aurococci as well as features of their morpho-functional reaction by atomic force microscopy. The study was carried out in 12 Staphylococcus aureus clones isolated from mucous membrane of nose anterior part of a resident carrier. The effect of cycloferon in vivo was evaluated in 26 resident staphylococci carriers under the control of anti-carnosine activity of staphylococci. Anti-carnosine activity was determined by O.V. Bukharin et al. (1999), biofilm formation -by G.A. O'Toole et al. (2000). Staphylococci treated with cycloferon were studied by atomic force microscopy in contact mode using scanning probe SMM-2000 microscope. The decrease of persistence properties of staphylococci under the effect of cycloferon in vitro and in vivo may be examined as one of the mechanisms of biological activity of the preparation. A significant increase of S. aureus surface roughness and changes in their morphology under the effect of cycloferon allow stating the disorder of barrier functions in the aurococci cell wall. The data obtained expand the understanding of cycloferon biological activity mechanisms.

Construction of Biologically Functional Bacterial Plasmids In Vitro

Science.gov (United States)

Cohen, Stanley N.; Chang, Annie C. Y.; Boyer, Herbert W.; Helling, Robert B.

1973-01-01

The construction of new plasmid DNA species by in vitro joining of restriction endonuclease-generated fragments of separate plasmids is described. Newly constructed plasmids that are inserted into Escherichia coli by transformation are shown to be biologically functional replicons that possess genetic properties and nucleotide base sequences from both of the parent DNA molecules. Functional plasmids can be obtained by reassociation of endonuclease-generated fragments of larger replicons, as well as by joining of plasmid DNA molecules of entirely different origins. Images PMID:4594039

2009 Archaea: Ecology, Metabolism & Molecular Biology GRC

Energy Technology Data Exchange (ETDEWEB)

Furlow, Julie Maupin- [Univ. of Florida, Gainesville, FL (United States)

2009-07-26

Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses; and industrial applications. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

Marine Carotenoids: Biological Functions and Commercial Applications

Science.gov (United States)

Vílchez, Carlos; Forján, Eduardo; Cuaresma, María; Bédmar, Francisco; Garbayo, Inés; Vega, José M.

2011-01-01

Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological functions of carotenoids relevant for life on earth. Biological properties of carotenoids allow for a wide range of commercial applications. Indeed, recent interest in the carotenoids has been mainly for their nutraceutical properties. A large number of scientific studies have confirmed the benefits of carotenoids to health and their use for this purpose is growing rapidly. In addition, carotenoids have traditionally been used in food and animal feed for their color properties. Carotenoids are also known to improve consumer perception of quality; an example is the addition of carotenoids to fish feed to impart color to farmed salmon. PMID:21556162

ExpandED Options: Learning beyond High School Walls

Science.gov (United States)

ExpandED Schools, 2014

2014-01-01

Through ExpandED Options by TASC, New York City high school students get academic credit for learning career-related skills that lead to paid summer jobs. Too many high school students--including those most likely to drop out--are bored or see classroom learning as irrelevant. ExpandED Options students live the connection between mastering new…

Biological properties of extracellular vesicles and their physiological functions

Directory of Open Access Journals (Sweden)

María Yáñez-Mó

2015-05-01

Full Text Available In the past decade, extracellular vesicles (EVs have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Biological properties of extracellular vesicles and their physiological functions

Science.gov (United States)

Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier

2015-01-01

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

The ISCB Student Council Internship Program: Expanding computational biology capacity worldwide.

Science.gov (United States)

Anupama, Jigisha; Francescatto, Margherita; Rahman, Farzana; Fatima, Nazeefa; DeBlasio, Dan; Shanmugam, Avinash Kumar; Satagopam, Venkata; Santos, Alberto; Kolekar, Pandurang; Michaut, Magali; Guney, Emre

2018-01-01

Education and training are two essential ingredients for a successful career. On one hand, universities provide students a curriculum for specializing in one's field of study, and on the other, internships complement coursework and provide invaluable training experience for a fruitful career. Consequently, undergraduates and graduates are encouraged to undertake an internship during the course of their degree. The opportunity to explore one's research interests in the early stages of their education is important for students because it improves their skill set and gives their career a boost. In the long term, this helps to close the gap between skills and employability among students across the globe and balance the research capacity in the field of computational biology. However, training opportunities are often scarce for computational biology students, particularly for those who reside in less-privileged regions. Aimed at helping students develop research and academic skills in computational biology and alleviating the divide across countries, the Student Council of the International Society for Computational Biology introduced its Internship Program in 2009. The Internship Program is committed to providing access to computational biology training, especially for students from developing regions, and improving competencies in the field. Here, we present how the Internship Program works and the impact of the internship opportunities so far, along with the challenges associated with this program.

The ISCB Student Council Internship Program: Expanding computational biology capacity worldwide.

Directory of Open Access Journals (Sweden)

Jigisha Anupama

2018-01-01

Full Text Available Education and training are two essential ingredients for a successful career. On one hand, universities provide students a curriculum for specializing in one's field of study, and on the other, internships complement coursework and provide invaluable training experience for a fruitful career. Consequently, undergraduates and graduates are encouraged to undertake an internship during the course of their degree. The opportunity to explore one's research interests in the early stages of their education is important for students because it improves their skill set and gives their career a boost. In the long term, this helps to close the gap between skills and employability among students across the globe and balance the research capacity in the field of computational biology. However, training opportunities are often scarce for computational biology students, particularly for those who reside in less-privileged regions. Aimed at helping students develop research and academic skills in computational biology and alleviating the divide across countries, the Student Council of the International Society for Computational Biology introduced its Internship Program in 2009. The Internship Program is committed to providing access to computational biology training, especially for students from developing regions, and improving competencies in the field. Here, we present how the Internship Program works and the impact of the internship opportunities so far, along with the challenges associated with this program.

Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations

Directory of Open Access Journals (Sweden)

Gloria Mazzone

2016-02-01

Full Text Available The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600–800 nm. The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenylchlorin (Foscan© already used in the photodynamic therapy (PDT protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents.

The functioning and behaviour of biological parents of children ...

African Journals Online (AJOL)

Parenting a child with ADHD may intensify parental stress through functional impairment notwithstanding the diagnosis of ADHD. Methods: Eighty-one biological parents of children diagnosed with attention-deficit/ hyperactivity disorder were screened using self-reporting measurements. ADHD self-report scale (ASRS-V 1.1) ...

Aortic annulus eccentricity before and after transcatheter aortic valve implantation: Comparison of balloon-expandable and self-expanding prostheses

International Nuclear Information System (INIS)

Schuhbaeck, Annika; Weingartner, Christina; Arnold, Martin; Schmid, Jasmin; Pflederer, Tobias; Marwan, Mohamed; Rixe, Johannes; Nef, Holger; Schneider, Christian; Lell, Michael; Uder, Michael; Ensminger, Stephan; Feyrer, Richard; Weyand, Michael; Achenbach, Stephan

2015-01-01

Highlights: • Post-implant geometry of catheter-based aortic valve prostheses is influenced by aortic valve calcification. • Balloon-expandable prostheses are more circular as compared to self-expanding prostheses. • The impact of post-implant geometry on valve function needs to be investigated. - Abstract: Introduction: The geometry of the aortic annulus and implanted transcatheter aortic valve prosthesis might influence valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of catheter-based aortic valve prostheses. Methods: Eighty consecutive patients with severe aortic valve stenosis (mean age 82 ± 6 years) underwent computed tomography before and after TAVI. Aortic annulus diameters were determined. Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity were analysed. Results: Aortic annulus eccentricity was reduced in patients after TAVI (0.21 ± 0.06 vs. 0.08 ± 0.06, p < 0.0001). Post-TAVI eccentricity was significantly lower in 65 patients following implantation of a balloon-expandable prosthesis as compared to 15 patients who received a self-expanding prosthesis (0.06 ± 0.05 vs. 0.15 ± 0.07, p < 0.0001), even though the extent of aortic valve calcification was not different. After TAVI, patients with a higher calcium amount retained a significantly higher eccentricity compared to patients with lower amounts of calcium. Conclusions: Patients undergoing TAVI with a balloon-expandable prosthesis show a more circular shape of the implanted prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification

N-acylation of phosphatidylethanolamine and its biological functions in mammals

DEFF Research Database (Denmark)

Wellner, Niels; Diep, Thi Ai; Janfelt, Christian

2013-01-01

N-acylphosphatidylethanolamine (NAPE) and N-acylplasmenylethanolamine (pNAPE) are widely found phospholipids, and they are precursors for N-acylethanolamines, a group of compounds that has a variety of biological effects and encompasses the endocannabinoid anandamide. NAPE and pNAPE are synthesiz...... reviews the metabolism, occurrence and assay of NAPE and pNAPE, and discusses the putative biological functions in mammals of these phospholipids. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism....

Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

Science.gov (United States)

Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

2016-10-20

The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks.

Science.gov (United States)

Li, Min; Li, Dongyan; Tang, Yu; Wu, Fangxiang; Wang, Jianxin

2017-08-31

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster.

Data Transformation Functions for Expanded Search Spaces in Geographic Sample Supervised Segment Generation

Directory of Open Access Journals (Sweden)

Christoff Fourie

2014-04-01

Full Text Available Sample supervised image analysis, in particular sample supervised segment generation, shows promise as a methodological avenue applicable within Geographic Object-Based Image Analysis (GEOBIA. Segmentation is acknowledged as a constituent component within typically expansive image analysis processes. A general extension to the basic formulation of an empirical discrepancy measure directed segmentation algorithm parameter tuning approach is proposed. An expanded search landscape is defined, consisting not only of the segmentation algorithm parameters, but also of low-level, parameterized image processing functions. Such higher dimensional search landscapes potentially allow for achieving better segmentation accuracies. The proposed method is tested with a range of low-level image transformation functions and two segmentation algorithms. The general effectiveness of such an approach is demonstrated compared to a variant only optimising segmentation algorithm parameters. Further, it is shown that the resultant search landscapes obtained from combining mid- and low-level image processing parameter domains, in our problem contexts, are sufficiently complex to warrant the use of population based stochastic search methods. Interdependencies of these two parameter domains are also demonstrated, necessitating simultaneous optimization.

Metabolomics for functional genomics, systems biology, and biotechnology.

Science.gov (United States)

Saito, Kazuki; Matsuda, Fumio

2010-01-01

Metabolomics now plays a significant role in fundamental plant biology and applied biotechnology. Plants collectively produce a huge array of chemicals, far more than are produced by most other organisms; hence, metabolomics is of great importance in plant biology. Although substantial improvements have been made in the field of metabolomics, the uniform annotation of metabolite signals in databases and informatics through international standardization efforts remains a challenge, as does the development of new fields such as fluxome analysis and single cell analysis. The principle of transcript and metabolite cooccurrence, particularly transcriptome coexpression network analysis, is a powerful tool for decoding the function of genes in Arabidopsis thaliana. This strategy can now be used for the identification of genes involved in specific pathways in crops and medicinal plants. Metabolomics has gained importance in biotechnology applications, as exemplified by quantitative loci analysis, prediction of food quality, and evaluation of genetically modified crops. Systems biology driven by metabolome data will aid in deciphering the secrets of plant cell systems and their application to biotechnology.

MicroRNA functional network in pancreatic cancer: From biology to ...

Indian Academy of Sciences (India)

[Wang J and Sen S 2011 MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease. ... growth factor type I receptor; INSR, insulin receptor; IPA, Ingenuity Pathway Analysis; IPMN, ..... Prostate cancer signalling.

First order phase transition of expanding matter and its fragmentation

International Nuclear Information System (INIS)

Chikazumi, Shinpei; Iwamoto, Akira

2002-01-01

Using an expanding matter model with a Lennard-Jones potential, the instability of the expanding system is investigated. The pressure, the temperature, and the density fluctuations are calculated as functions of density during the time evolution of the expanding matter, which are compared to the coexistence curve calculated by the Gibbs ensemble. The expanding matter undergoes the first order phase transition in the limit of the quasistatic expansion. The resultant fragment mass distributions are also investigated. (author)

Free-piston reciprocating cryogenic expander utilizing phase controller

Science.gov (United States)

Cha, Jeongmin; Park, Jiho; Kim, Kyungjoong; Jeong, Sangkwon

2017-02-01

In a free-piston expander which eliminates mechanical linkages, a prescribed behaviour of the free-piston movement is the key to an expander performance. In this paper, we have proposed an idea of reducing complexity of the free-piston expander. It is to replace both multiple solenoid valves and reservoirs that are indispensable in a previous machine with a combination of a single orifice-reservoir assembly. It functions as a phase controller like that of a pulse tube refrigerator so that it generates time-delay of pressure variation between the warm-end and the reservoir resulting in the intended expansion of the cold-end volume down to the pre-set reservoir pressure. The modeling of this unique free-piston reciprocating expander utilizing phase controller is developed to understand and predict the performance of the new-type expander. Additionally, the operating parameters are analysed at the specified conditions to enable one to develop a more efficient free-piston type cryogenic expander.

The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

Directory of Open Access Journals (Sweden)

Sathish ePeriyasamy

2013-12-01

Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

Science.gov (United States)

Lovering, Ruth C; Roncaglia, Paola; Howe, Douglas G; Laulederkind, Stanley J F; Khodiyar, Varsha K; Berardini, Tanya Z; Tweedie, Susan; Foulger, Rebecca E; Osumi-Sutherland, David; Campbell, Nancy H; Huntley, Rachael P; Talmud, Philippa J; Blake, Judith A; Breckenridge, Ross; Riley, Paul R; Lambiase, Pier D; Elliott, Perry M; Clapp, Lucie; Tinker, Andrew; Hill, David P

2018-02-01

A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. © 2018 The Authors.

Virtual Agonist-antagonist Mechanisms Produce Biological Muscle-like Functions: An Application for Robot Joint Control

DEFF Research Database (Denmark)

Xiong, Xiaofeng; Wörgötter, Florentin; Manoonpong, Poramate

2014-01-01

Purpose – Biological muscles of animals have a surprising variety of functions, i.e., struts, springs, and brakes. According to this, the purpose of this paper is to apply virtual agonist-antagonist mechanisms to robot joint control allowing for muscle-like functions and variably compliant joint......, variably compliant joint motions can be produced without mechanically bulky and complex mechanisms or complex force/toque sensing at each joint. Moreover, through tuning the damping coefficient of the VAAM, the functions of the VAAM are comparable to biological muscles. Originality/value – The model (i.......e., VAAM) provides a way forward to emulate muscle-like functions that are comparable to those found in physiological experiments of biological muscles. Based on these muscle-like functions, the robotic joints can easily achieve variable compliance that does not require complex physical components...

Scavenger Receptor CD163 and Its Biological Functions

Directory of Open Access Journals (Sweden)

Gabriela Onofre

2009-01-01

Full Text Available CD163 is a member of scavenger receptor super family class B of the first subgroup. It is mapped to the region p13 on chromosome 12. Five different isoforms of CD163 have been described, which differ in the structure of their cytoplasmic domains and putative phosporylation sites. This scavenger receptor is selectively expressed on cells of monocytes and macrophages lineage exclusively. CD163 immunological function is essentially homeostatic. It also has other functions because participates in adhesion to endothelial cells, in tolerance induction and tissues regeneration. Other very important function of CD163 is the clearance of hemoglobin in its cell-free form and participation in anti-inflammation in its soluble form, exhibiting cytokine-like functions. We review the biological functions of CD163 which have been discovered until now. It seems apparent from this review that CD163 scavenger receptor can be used as biomarker in different diseases and as a valuable diagnostic parameter for prognosis of many diseases especially inflammatory disorders and sepsis.

Carotenoids from Marine Organisms: Biological Functions and Industrial Applications

Directory of Open Access Journals (Sweden)

Christian Galasso

2017-11-01

Full Text Available As is the case for terrestrial organisms, carotenoids represent the most common group of pigments in marine environments. They are generally biosynthesized by all autotrophic marine organisms, such as bacteria and archaea, algae and fungi. Some heterotrophic organisms also contain carotenoids probably accumulated from food or partly modified through metabolic reactions. These natural pigments are divided into two chemical classes: carotenes (such as lycopene and α- and β-carotene that are composed of hydrogen and carbon; xanthophylls (such as astaxanthin, fucoxanthin and lutein, which are constituted by hydrogen, carbon and oxygen. Carotenoids, as antioxidant compounds, assume a key role in the protection of cells. In fact, quenching of singlet oxygen, light capture and photosynthesis protection are the most relevant biological functions of carotenoids. The present review aims at describing (i the biological functions of carotenoids and their benefits for human health, (ii the most common carotenoids from marine organisms and (iii carotenoids having large success in pharmaceutical, nutraceutical and cosmeceutical industries, highlighting the scientific progress in marine species cultivation for natural pigments production.

Neurotrophin Propeptides: Biological Functions and Molecular Mechanisms.

Science.gov (United States)

Rafieva, Lola M; Gasanov, Eugene V

2016-01-01

Neurotrophins constitute a family of growth factors that play a key role in the regulation of the development and function of the central and peripheral nervous systems. A common feature of all the neurotrophins is their synthesis in cells as long precursors (pre-pro-neurotrophins) that contain an N-terminal signal peptide, a following propeptide and the mature neurotrophin. Although the signal peptide functions have been well studied, the role of neurotrophin propeptides is not so clear. Here, we briefly summarize the biochemistry of neurotrophin propeptides, including their role as folding-assistants for the mature factor and their role in processing and in secretion of neurotrophins. In the main part of the review we summarize our current state of knowledge of the biological activity of neurotrophin propeptides, their possible mechanisms of action, and their potential influence on the activity of the mature neurotrophins.

RNA and RNP as Building Blocks for Nanotechnology and Synthetic Biology.

Science.gov (United States)

Ohno, Hirohisa; Saito, Hirohide

2016-01-01

Recent technologies that aimed to elucidate cellular function have revealed essential roles for RNA molecules in living systems. Our knowledge concerning functional and structural information of naturally occurring RNA and RNA-protein (RNP) complexes is increasing rapidly. RNA and RNP interaction motifs are structural units that function as building blocks to constitute variety of complex structures. RNA-central synthetic biology and nanotechnology are constructive approaches that employ the accumulated information and build synthetic RNA (RNP)-based circuits and nanostructures. Here, we describe how to design and construct synthetic RNA (RNP)-based devices and structures at the nanometer-scale for biological and future therapeutic applications. RNA/RNP nanostructures can also be utilized as the molecular scaffold to control the localization or interactions of target molecule(s). Moreover, RNA motifs recognized by RNA-binding proteins can be applied to make protein-responsive translational "switches" that can turn gene expression "on" or "off" depending on the intracellular environment. This "synthetic RNA and RNP world" will expand tools for nanotechnology and synthetic biology. In addition, these reconstructive approaches would lead to a greater understanding of building principle in naturally occurring RNA/RNP molecules and systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthetic Biology of Cyanobacteria: Unique Challenges and Opportunities

Directory of Open Access Journals (Sweden)

Bertram M Berla

2013-08-01

Full Text Available Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria’s potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as ‘chassis’ strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a ‘green E. coli’. In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints.

Re-evaluating concepts of biological function in clinical medicine: towards a new naturalistic theory of disease.

Science.gov (United States)

Chin-Yee, Benjamin; Upshur, Ross E G

2017-08-01

Naturalistic theories of disease appeal to concepts of biological function, and use the notion of dysfunction as the basis of their definitions. Debates in the philosophy of biology demonstrate how attributing functions in organisms and establishing the function-dysfunction distinction is by no means straightforward. This problematization of functional ascription has undermined naturalistic theories and led some authors to abandon the concept of dysfunction, favoring instead definitions based in normative criteria or phenomenological approaches. Although this work has enhanced our understanding of disease and illness, we need not necessarily abandon naturalistic concepts of function and dysfunction in the disease debate. This article attempts to move towards a new naturalistic theory of disease that overcomes the limitations of previous definitions and offers advantages in the clinical setting. Our approach involves a re-evaluation of concepts of biological function employed by naturalistic theories. Drawing on recent insights from the philosophy of biology, we develop a contextual and evaluative account of function that is better suited to clinical medicine and remains consistent with contemporary naturalism. We also show how an updated naturalistic view shares important affinities with normativist and phenomenological positions, suggesting a possibility for consilience in the disease debate.

The relationship between oral health status and biological and psychosocial function in the bedridden elderly.

Science.gov (United States)

Hanada, N; Tada, A

2001-01-01

The present study was conducted in order to determine what item of biological and psychosocial function is related to oral health status in the bedridden elderly. The subjects were 94 elderly individuals (30 males, 64 females) who had been admitted to a nursing home in Chiba city, Japan. We assessed the number of remaining teeth and the number of functional teeth as oral health status variables. Biological and psychosocial function levels were determined using the functional independence measure method developed by the State University of New York at Buffalo. More than 70% of subjects had less than ten remaining teeth. Almost all subjects needed prosthesis treatment. More than 50% of subjects had 27 or less functional teeth. Mann-Whitney U-test and logistic regression models showed that 'expression' was concerned with the number of remaining teeth and 'bladder management', 'locomotion', 'transfers' were related to the number of functional teeth. These data suggest close relation between oral health status and biological and psychosocial function levels in the bedridden elderly.

Paul Langerhans: a prilgrim "traveling" from functional histology to marine biology.

Science.gov (United States)

Raica, Marius; Cimpean, Anca Maria

2017-06-01

The nineteenth century was the time of a real revolution in science and medicine. A lot of seminal discoveries in medicine and biology were done in this time, and many of them were coincident with the introduction of the compound microscope by Hermann van Deijl and the standard histological technique by Paul Ehrlich. The main tissue types and individual cells were characterized and originally classified more than hundred years ago, although less attention was paid to their basic functions. This was mainly due to the modality of tissue specimen processing that allowed particularly detailed descriptive studies. Even so, we can notice some attempts to correlate the structure with the function. The German scientist Paul Langerhans, well-known for the discovery of Langerhans islets of the pancreas and Langerhans cells from the epidermis, tried to change the conventional fate of morphological studies introducing in his works functional hypothesis based on traditional microscopic observations even from the beginning of his scientific career. Paul Langerhans was a complex personality of the second half of the nineteenth century, not only in medicine, but also in other fields of biology. In the present review, presented is the life and research activity of Paul Langerhans, not only because of the importance of his discoveries, but also for perspectives that were opened by these findings in unexpected fields of medicine and biology.

Knowledge base and functionality of concepts of some Filipino biology teachers in five biology topics

Science.gov (United States)

Barquilla, Manuel B.

2018-01-01

This mixed research, is a snapshot of some Filipino Biology teachers' knowledge structure and how their concepts of the five topics in Biology (Photosynthesis, Cellular Respiration, human reproductive system, Mendelian genetics and NonMendelian genetics) functions and develops inside a biology classroom. The study focuses on the six biology teachers and a total of 222 students in their respective classes. Of the Six (6) teachers, three (3) are under the Science curriculum and the other three (3) are under regular curriculum in both public and private schools in Iligan city and Lanao del Norte, Philippines. The study utilized classroom discourses, concept maps, interpretative case-study method, bracketing method, and concept analysis for qualitative part; the quantitative part uses a nonparametric statistical tool, Kendall's tau Coefficient for determining relationship and congruency while measures of central tendencies and dispersion (mean, and standard deviation) for concept maps scores interpretation. Knowledge Base of Biology teachers were evaluated by experts in field of specialization having a doctorate program (e.g. PhD in Genetics) and PhD Biology candidates. The data collection entailed seven (7) months immersion: one (1) month for preliminary phase for the researcher to gain teachers' and students' confidence and the succeeding six (6) months for main observation and data collection. The evaluation of teachers' knowledge base by experts indicated that teachers' knowledge of (65%) is lower than the minimum (75%) recommended by ABD-el-Khalick and Boujaoude (1997). Thus, the experts believe that content knowledge of the teachers is hardly adequate for their teaching assignment. Moreover, the teachers in this study do not systematically use reallife situation to apply the concepts they teach. They can identify concepts too abstract for their student; however, they seldom use innovative ways to bring the discussion to their students' level of readiness and

Expanding the Bethe/Gauge dictionary

Science.gov (United States)

Bullimore, Mathew; Kim, Hee-Cheol; Lukowski, Tomasz

2017-11-01

We expand the Bethe/Gauge dictionary between the XXX Heisenberg spin chain and 2d N = (2, 2) supersymmetric gauge theories to include aspects of the algebraic Bethe ansatz. We construct the wave functions of off-shell Bethe states as orbifold defects in the A-twisted supersymmetric gauge theory and study their correlation functions. We also present an alternative description of off-shell Bethe states as boundary conditions in an effective N = 4 supersymmetric quantum mechanics. Finally, we interpret spin chain R-matrices as correlation functions of Janus interfaces for mass parameters in the supersymmetric quantum mechanics.

Progress in the biological function of alpha-enolase

Directory of Open Access Journals (Sweden)

Hong Ji

2016-03-01

Full Text Available Alpha-enolase (ENO1, also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid in the glycolytic pathway. It is a multifunctional glycolytic enzyme involved in cellular stress, bacterial and fungal infections, autoantigen activities, the occurrence and metastasis of cancer, parasitic infections, and the growth, development and reproduction of organisms. This article mainly reviews the basic characteristics and biological functions of ENO1.

Biological markers for kidney injury and renal function in the intensive care unit

NARCIS (Netherlands)

Royakkers, A.A.N.M.

2014-01-01

The purpose of the investigations described in this thesis was to seek for answers to two relevant questions in ICUs in resource-rich settings, i.e., can new biological markers play a role in early recognition of AKI, and can new biological markers predict recovery of renal function in patients who

Tissue expander infections in children: look beyond the expander pocket.

Science.gov (United States)

Mason, A C; Davison, S P; Manders, E K

1999-11-01

Infection of the expander pocket is the most common complication encountered with soft-tissue expansion. It is usually due to direct inoculation with skin flora either at the time of expander insertion or from extrusion of the device. The authors report two cases of infection of tissue expanders in which the children had concomitant infected sites distant from the prosthesis. Etiological bacteria of common pediatric infections like otitis media and pharyngitis were cultured from the infected expander pocket, raising suspicion that translocation of the organism to the expander had occurred. Aggressive antibiotic treatment, removal of the prosthesis, and flap advancement is advocated.

Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions.

Science.gov (United States)

Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Uversky, Vladimir N; Obradovic, Zoran

2007-05-01

Identifying relationships between function, amino acid sequence, and protein structure represents a major challenge. In this study, we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from the Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins, and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our

[Recent advances of synthetic biology for production of functional ingredients in Chinese materia medica].

Science.gov (United States)

Su, Xin-Yao; Xue, Jian-Ping; Wang, Cai-Xia

2016-11-01

The functional ingredients in Chinese materia medica are the main active substance for traditional Chinese medicine and most of them are secondary metabolites derivatives. Until now,the main method to obtain those functional ingredients is through direct extraction from the Chinese materia medica. However, the income is very low because of the high extraction costs and the decreased medicinal plants. Synthetic biology technology, as a new and microbial approach, can be able to carry out large-scale production of functional ingredients and greatly ease the shortage of traditional Chinese medicine ingredients. This review mainly focused on the recent advances in synthetic biology for the functional ingredients production. Copyright© by the Chinese Pharmaceutical Association.

Mediating objects: scientific and public functions of models in nineteenth-century biology.

Science.gov (United States)

Ludwig, David

2013-01-01

The aim of this article is to examine the scientific and public functions of two- and three-dimensional models in the context of three episodes from nineteenth-century biology. I argue that these models incorporate both data and theory by presenting theoretical assumptions in the light of concrete data or organizing data through theoretical assumptions. Despite their diverse roles in scientific practice, they all can be characterized as mediators between data and theory. Furthermore, I argue that these different mediating functions often reflect their different audiences that included specialized scientists, students, and the general public. In this sense, models in nineteenth-century biology can be understood as mediators between theory, data, and their diverse audiences.

Biomarkers of Aging: From Function to Molecular Biology

Directory of Open Access Journals (Sweden)

Karl-Heinz Wagner

2016-06-01

Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

Automated quantitative assessment of proteins' biological function in protein knowledge bases.

Science.gov (United States)

Mayr, Gabriele; Lepperdinger, Günter; Lackner, Peter

2008-01-01

Primary protein sequence data are archived in databases together with information regarding corresponding biological functions. In this respect, UniProt/Swiss-Prot is currently the most comprehensive collection and it is routinely cross-examined when trying to unravel the biological role of hypothetical proteins. Bioscientists frequently extract single entries and further evaluate those on a subjective basis. In lieu of a standardized procedure for scoring the existing knowledge regarding individual proteins, we here report about a computer-assisted method, which we applied to score the present knowledge about any given Swiss-Prot entry. Applying this quantitative score allows the comparison of proteins with respect to their sequence yet highlights the comprehension of functional data. pfs analysis may be also applied for quality control of individual entries or for database management in order to rank entry listings.

Automated Quantitative Assessment of Proteins' Biological Function in Protein Knowledge Bases

Directory of Open Access Journals (Sweden)

Gabriele Mayr

2008-01-01

Full Text Available Primary protein sequence data are archived in databases together with information regarding corresponding biological functions. In this respect, UniProt/Swiss-Prot is currently the most comprehensive collection and it is routinely cross-examined when trying to unravel the biological role of hypothetical proteins. Bioscientists frequently extract single entries and further evaluate those on a subjective basis. In lieu of a standardized procedure for scoring the existing knowledge regarding individual proteins, we here report about a computer-assisted method, which we applied to score the present knowledge about any given Swiss-Prot entry. Applying this quantitative score allows the comparison of proteins with respect to their sequence yet highlights the comprehension of functional data. pfs analysis may be also applied for quality control of individual entries or for database management in order to rank entry listings.

Exploring candidate biological functions by Boolean Function Networks for Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Maria Simak

Full Text Available The great amount of gene expression data has brought a big challenge for the discovery of Gene Regulatory Network (GRN. For network reconstruction and the investigation of regulatory relations, it is desirable to ensure directness of links between genes on a map, infer their directionality and explore candidate biological functions from high-throughput transcriptomic data. To address these problems, we introduce a Boolean Function Network (BFN model based on techniques of hidden Markov model (HMM, likelihood ratio test and Boolean logic functions. BFN consists of two consecutive tests to establish links between pairs of genes and check their directness. We evaluate the performance of BFN through the application to S. cerevisiae time course data. BFN produces regulatory relations which show consistency with succession of cell cycle phases. Furthermore, it also improves sensitivity and specificity when compared with alternative methods of genetic network reverse engineering. Moreover, we demonstrate that BFN can provide proper resolution for GO enrichment of gene sets. Finally, the Boolean functions discovered by BFN can provide useful insights for the identification of control mechanisms of regulatory processes, which is the special advantage of the proposed approach. In combination with low computational complexity, BFN can serve as an efficient screening tool to reconstruct genes relations on the whole genome level. In addition, the BFN approach is also feasible to a wide range of time course datasets.

Single amino acid substitution in important hemoglobinopathies does not disturb molecular function and biological process

Directory of Open Access Journals (Sweden)

Viroj Wiwanitkit

2008-06-01

Full Text Available Viroj WiwanitkitDepartment of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: Hemoglobin is an important protein found in the red cells of many animals. In humans, the hemoglobin is mainly distributed in the red blood cell. Single amino acid substitution is the main pathogenesis of most hemoglobin disorders. Here, the author used a new gene ontology technology to predict the molecular function and biological process of four important hemoglobin disorders with single substitution. The four studied important abnormal hemoglobins (Hb with single substitution included Hb S, Hb E, Hb C, and Hb J-Baltimore. Using the GoFigure server, the molecular function and biological process in normal and abnormal hemoglobins was predicted. Compared with normal hemoglobin, all studied abnormal hemoglobins had the same function and biological process. This indicated that the overall function of oxygen transportation is not disturbed in the studied hemoglobin disorders. Clinical findings of oxygen depletion in abnormal hemoglobin should therefore be due to the other processes rather than genomics, proteomics, and expression levels.Keywords: hemoglobin, amino acid, substitution, function

Expanded porphyrins as third order non-linear optical materials ...

Indian Academy of Sciences (India)

WINTEC

function correlations ... An understanding of the structure–function corre- lations of these expanded porphyrins is an important first step for ... where χ (2) and χ (3) are the quadratic χ (2) (first- order) and χ (3) cubic (second-order) susceptibilities.

Event-based text mining for biology and functional genomics

Science.gov (United States)

Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

2015-01-01

The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

Functional Anthology of Intrinsic Disorder. I. Biological Processes and Functions of Proteins with Long Disordered Regions

Science.gov (United States)

Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Uversky, Vladimir N.; Obradovic, Zoran

2008-01-01

Identifying relationships between function, amino acid sequence and protein structure represents a major challenge. In this study we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our statistical

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

Science.gov (United States)

Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

2016-11-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

Cell-free synthetic biology for in vitro prototype engineering.

Science.gov (United States)

Moore, Simon J; MacDonald, James T; Freemont, Paul S

2017-06-15

Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. © 2017 The Author(s).

Esophagorespiratory fistula: treatment with self-expanding covered stent

International Nuclear Information System (INIS)

Zang Jian; Dou Yongchong; Wang Zheng; Kong Jian

2002-01-01

Objective: To evaluate self-expanding covered stent in the management of esophagorespiratory fistula. Methods: A self-expanding esophageal covered stent was implanted under fluoroscopic guidance in 13 patients with esophagorespiratory fistula. In this series patients aged 31-73 years (60.2 years in average). All patients had a pre-procedure fast of 6-41 days (17.3 days in average), in which 12 patients had pulmonary infection. Results: All fistulas were excluded and swallowing function was restored. No stend-related complication was observed. Pulmonary infection was managed in 10 patients out of 13. The mean survived time was 33.3 wks (1-178 wks) in follow-up. Conclusion: Covered self-expanding stent implantation is a safe and effective treatment of ERF

Expandable Total Humeral Replacement in a Child with Osteosarcoma

Directory of Open Access Journals (Sweden)

Eric R. Henderson

2015-01-01

Full Text Available Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option.

The functional biology of human milk oligosaccharides.

Science.gov (United States)

Bode, Lars

2015-11-01

Human milk oligosaccharides (HMOs) are a group of complex sugars that are highly abundant in human milk, but currently not present in infant formula. More than a hundred different HMOs have been identified so far. The amount and composition of HMOs are highly variable between women, and each structurally defined HMO might have a distinct functionality. HMOs are not digested by the infant and serve as metabolic substrates for select microbes, contributing to shape the infant gut microbiome. HMOs act as soluble decoy receptors that block the attachment of viral, bacterial or protozoan parasite pathogens to epithelial cell surface sugars, which may help prevent infectious diseases in the gut and also the respiratory and urinary tracts. HMOs are also antimicrobials that act as bacteriostatic or bacteriocidal agents. In addition, HMOs alter host epithelial and immune cell responses with potential benefits for the neonate. The article reviews current knowledge as well as future challenges and opportunities related to the functional biology of HMOs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The 11S Proteasomal Activator REGγ Impacts Polyglutamine-Expanded Androgen Receptor Aggregation and Motor Neuron Viability through Distinct Mechanisms

Directory of Open Access Journals (Sweden)

Jill M. Yersak

2017-05-01

Full Text Available Spinal and bulbar muscular atrophy (SBMA is caused by expression of a polyglutamine (polyQ-expanded androgen receptor (AR. The inefficient nuclear proteasomal degradation of the mutant AR results in the formation of nuclear inclusions containing amino-terminal fragments of the mutant AR. PA28γ (also referred to as REGγ is a nuclear 11S-proteasomal activator with limited proteasome activation capabilities compared to its cytoplasmic 11S (PA28α, PA28β counterparts. To clarify the role of REGγ in polyQ-expanded AR metabolism, we carried out genetic and biochemical studies in cell models of SBMA. Overexpression of REGγ in a PC12 cell model of SBMA increased polyQ-expanded AR aggregation and contributed to polyQ-expanded AR toxicity in the presence of dihydrotestosterone (DHT. These effects of REGγ were independent of its association with the proteasome and may be due, in part, to the decreased binding of polyQ-expanded AR by the E3 ubiquitin-ligase MDM2. Unlike its effects in PC12 cells, REGγ overexpression rescued transgenic SBMA motor neurons from DHT-induced toxicity in a proteasome binding-dependent manner, suggesting that the degradation of a specific 11S proteasome substrate or substrates promotes motor neuron viability. One potential substrate that we found to play a role in mutant AR toxicity is the splicing factor SC35. These studies reveal that, depending on the cellular context, two biological roles for REGγ impact cell viability in the face of polyQ-expanded AR; a proteasome binding-independent mechanism directly promotes mutant AR aggregation while a proteasome binding-dependent mechanism promotes cell viability. The balance between these functions likely determines REGγ effects on polyQ-expanded AR-expressing cells.

Expandable stents.

Science.gov (United States)

Nesbitt, J C; Carrasco, H

1996-05-01

Expandable metallic stents are effective in selected patients with malignant or benign airway stenoses. When used for malignant lesions, the primary purpose of the stent is to improve the quality of life; stents are usually chosen for palliation of symptoms in recognition of the low likelihood of success for other therapy. For patients with benign stenoses, the stents provide a permanent source of structural support to alleviate the narrowed segment. The advantages of the expandable metallic stents are as follows: (1) they can be inserted through an endotracheal tube or under local anesthesia with relative simplicity under fluoroscopic guidance; (2) they do not impair the drainage of sputum because ciliary movement is not interrupted; (3) over a period of a few weeks, the meshwork is gradually covered with mucosa as the stent becomes incorporated into the airway wall; (4) ventilation usually is not impaired if the metallic mesh stent covers another nonstenosed bronchus, because the interstices of the stent are nonobstructive; and (5) they are dynamic and continue to expand over time, particularly if concurrent treatment achieves an effect on the lesion that caused stenosis. Disadvantages of the expandable stent include (1) they often are only temporarily effective for tracheobronchial stenosis due to intraluminal tumor or granulation tissue, both of which can grow between the wires; (2) they are considered permanent stents because removal is difficult; and (3) they can be poorly positioned during placement or can become displaced by progressive migration after placement, and they cannot be repositioned. A relative contraindication to insertion is an inflammatory process or infection that can predispose to granulation formation, particularly at the points of maximal contact pressure of the stent to the airway mucosa. In the presence of inflammation, it may be better to use a silicone prosthesis until the inflammatory process subsides and fibrosis occurs. Granulation

Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits

Directory of Open Access Journals (Sweden)

Laura Mandolesi

2018-04-01

Full Text Available Much evidence shows that physical exercise (PE is a strong gene modulator that induces structural and functional changes in the brain, determining enormous benefit on both cognitive functioning and wellbeing. PE is also a protective factor for neurodegeneration. However, it is unclear if such protection is granted through modifications to the biological mechanisms underlying neurodegeneration or through better compensation against attacks. This concise review addresses the biological and psychological positive effects of PE describing the results obtained on brain plasticity and epigenetic mechanisms in animal and human studies, in order to clarify how to maximize the positive effects of PE while avoiding negative consequences, as in the case of exercise addiction.

The nucleic acid revolution continues - will forensic biology become forensic molecular biology?

Science.gov (United States)

Gunn, Peter; Walsh, Simon; Roux, Claude

2014-01-01

Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to "forensic molecular biology." Aside from DNA's established role in identifying the "who" in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about "when" a crime took place and "what" took place. However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future.

Lattice expansion of carbon-stabilized expanded austenite

DEFF Research Database (Denmark)

Hummelshøj, Thomas Strabo; Christiansen, Thomas; Somers, Marcel A. J.

2010-01-01

The lattice parameter of expanded austenite was determined as a function of the content of interstitially dissolved carbon in homogeneous, carburized thin stainless steel foils. For the first time this expansion of the face-centered cubic lattice is determined on unstrained austenite. It is found...

Expanded functional diversity of shaker K(+ channels in cnidarians is driven by gene expansion.

Directory of Open Access Journals (Sweden)

Timothy Jegla

Full Text Available The genome of the cnidarian Nematostella vectensis (starlet sea anemone provides a molecular genetic view into the first nervous systems, which appeared in a late common ancestor of cnidarians and bilaterians. Nematostella has a surprisingly large and diverse set of neuronal signaling genes including paralogs of most neuronal signaling molecules found in higher metazoans. Several ion channel gene families are highly expanded in the sea anemone, including three subfamilies of the Shaker K(+ channel gene family: Shaker (Kv1, Shaw (Kv3 and Shal (Kv4. In order to better understand the physiological significance of these voltage-gated K(+ channel expansions, we analyzed the function of 18 members of the 20 gene Shaker subfamily in Nematostella. Six of the Nematostella Shaker genes express functional homotetrameric K(+ channels in vitro. These include functional orthologs of bilaterian Shakers and channels with an unusually high threshold for voltage activation. We identified 11 Nematostella Shaker genes with a distinct "silent" or "regulatory" phenotype; these encode subunits that function only in heteromeric channels and serve to further diversify Nematostella Shaker channel gating properties. Subunits with the regulatory phenotype have not previously been found in the Shaker subfamily, but have evolved independently in the Shab (Kv2 family in vertebrates and the Shal family in a cnidarian. Phylogenetic analysis indicates that regulatory subunits were present in ancestral cnidarians, but have continued to diversity at a high rate after the split between anthozoans and hydrozoans. Comparison of Shaker family gene complements from diverse metazoan species reveals frequent, large scale duplication has produced highly unique sets of Shaker channels in the major metazoan lineages.

What Expands in an Expanding Universe?

Science.gov (United States)

Pacheco, José A De Freitas

2015-01-01

In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative) of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM) all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

What Expands in an Expanding Universe?

Directory of Open Access Journals (Sweden)

JOSÉ A. DE FREITAS PACHECO

2015-12-01

Full Text Available ABSTRACT In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

Bank Directors’ Perceptions of Expanded Auditor's Reports

DEFF Research Database (Denmark)

Boolaky, Pran Krishansing; Quick, Reiner

2016-01-01

Subsequent to the financial crisis, standard setters developed suggestions for enhancing the audit function, in order to increase financial stability. One related idea is to expand the audit report disclosed to the public, to ensure that it is fit for purpose. This study investigates the impact o...

A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

Science.gov (United States)

Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.

2013-01-01

SUMMARY Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks. PMID:22863014

AFM imaging of functionalized carbon nanotubes on biological membranes

International Nuclear Information System (INIS)

Lamprecht, C; Danzberger, J; Rangl, M; Gruber, H J; Hinterdorfer, P; Kienberger, F; Ebner, A; Liashkovich, I; Neves, V; Heister, E; Coley, H M; McFadden, J; Flahaut, E

2009-01-01

Multifunctional carbon nanotubes are promising for biomedical applications as their nano-size, together with their physical stability, gives access into the cell and various cellular compartments including the nucleus. However, the direct and label-free detection of carbon nanotube uptake into cells is a challenging task. The atomic force microscope (AFM) is capable of resolving details of cellular surfaces at the nanometer scale and thus allows following of the docking of carbon nanotubes to biological membranes. Here we present topographical AFM images of non-covalently functionalized single walled (SWNT) and double walled carbon nanotubes (DWNT) immobilized on different biological membranes, such as plasma membranes and nuclear envelopes, as well as on a monolayer of avidin molecules. We were able to visualize DWNT on the nuclear membrane while at the same time resolving individual nuclear pore complexes. Furthermore, we succeeded in localizing individual SWNT at the border of incubated cells and in identifying bundles of DWNT on cell surfaces by AFM imaging.

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

Science.gov (United States)

Dewhurst, Henry; Sundararaman, Niveda

2016-01-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

[BIOLOGICAL ACTIVITY OF ANTIMICROBIAL PEPTIDES FROM CHICKENS THROMBOCYTES].

Science.gov (United States)

Sycheva, M V; Vasilchenko, A S; Rogozhin, E A; Pashkova, T M; Popova, L P; Kartashova, O L

2016-01-01

Isolation and study of biological activity of antimicrobial peptides from chickens thrombocytes. Peptides from chickens thrombocytes, obtained by reverse-phase high-performance liquid chromatography method with stepped and linear gradients of concentration increase of the organic solvent were used in the study. Their antimicrobial activity was determined by microtitration method in broth; mechanism of biological effect--by using fluorescent spectroscopy method with DNA-tropic dyes. Individual fractions of peptides were isolated from chickens thrombocytes, that possess antimicrobial activity against Staphylococcus aureus P209 and Escherichia coli K12. A disruption of integrity of barrier structures of microorganisms under the effect of thrombocyte antimicrobial peptides and predominance of cells with damaged membrane in the population of E. coli was established. The data obtained on antimicrobial activity and mechanism of bactericidal effect of the peptide fractions from chickens thrombocytes isolated for the first time expand the understanding of functional properties of chickens thrombocytes and open a perspective for their further study with the aim of use as antimicrobial means.

The expanding universe of ribonucleoproteins: of novel RNA-binding proteins and unconventional interactions.

Science.gov (United States)

Beckmann, Benedikt M; Castello, Alfredo; Medenbach, Jan

2016-06-01

Post-transcriptional regulation of gene expression plays a critical role in almost all cellular processes. Regulation occurs mostly by RNA-binding proteins (RBPs) that recognise RNA elements and form ribonucleoproteins (RNPs) to control RNA metabolism from synthesis to decay. Recently, the repertoire of RBPs was significantly expanded owing to methodological advances such as RNA interactome capture. The newly identified RNA binders are involved in diverse biological processes and belong to a broad spectrum of protein families, many of them exhibiting enzymatic activities. This suggests the existence of an extensive crosstalk between RNA biology and other, in principle unrelated, cell functions such as intermediary metabolism. Unexpectedly, hundreds of new RBPs do not contain identifiable RNA-binding domains (RBDs), raising the question of how they interact with RNA. Despite the many functions that have been attributed to RNA, our understanding of RNPs is still mostly governed by a rather protein-centric view, leading to the idea that proteins have evolved to bind to and regulate RNA and not vice versa. However, RNPs formed by an RNA-driven interaction mechanism (RNA-determined RNPs) are abundant and offer an alternative explanation for the surprising lack of classical RBDs in many RNA-interacting proteins. Moreover, RNAs can act as scaffolds to orchestrate and organise protein networks and directly control their activity, suggesting that nucleic acids might play an important regulatory role in many cellular processes, including metabolism.

Preparation, quantitative surface analysis, intercalation characteristics and industrial implications of low temperature expandable graphite

Science.gov (United States)

Peng, Tiefeng; Liu, Bin; Gao, Xuechao; Luo, Liqun; Sun, Hongjuan

2018-06-01

Expandable graphite is widely used as a new functional carbon material, especially as fire-retardant; however, its practical application is limited due to the high expansion temperature. In this work, preparation process of low temperature and highly expandable graphite was studied, using natural flake graphite as raw material and KMnO4/HClO4/NH4NO3 as oxidative intercalations. The structure, morphology, functional groups and thermal properties were characterized during expanding process by Fourier transform infrared spectroscopy (FTIR), Raman spectra, thermo-gravimetry differential scanning calorimetry (TG-DSC), X-ray diffraction (XRD), and scanning electron microscope (SEM). The analysis showed that by oxidation intercalation, some oxygen-containing groups were grafted on the edge and within the graphite layer. The intercalation reagent entered the graphite layer to increase the interlayer spacing. After expansion, the original flaky expandable graphite was completely transformed into worm-like expanded graphite. The order of graphite intercalation compounds (GICs) was proposed and determined to be 3 for the prepared expandable graphite, based on quantitative XRD peak analysis. Meanwhile, the detailed intercalation mechanisms were also proposed. The comprehensive investigation paved a benchmark for the industrial application of such sulfur-free expanded graphite.

Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

Directory of Open Access Journals (Sweden)

Nocerino N

2014-03-01

Full Text Available Nunzia Nocerino,1 Andrea Fulgione,1 Marco Iannaccone,1 Laura Tomasetta,1 Flora Ianniello,1 Francesca Martora,1 Marco Lelli,2 Norberto Roveri,2 Federico Capuano,3 Rosanna Capparelli1 1Department of Agriculture Special Biotechnology Center Federico II, CeBIOTEC Biotechnology, University of Naples Federico II, Naples, 2Department of Chemistry, G Ciamician, Alma Mater Studiorum, University of Bologna, Bologna, 3Department of Food Inspection IZS ME, Naples, Italy Abstract: The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA. We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. Keywords: lactoferrin, hydroxyapatite nanocrystals, biomimetism, biological activity, drug delivery

WebBio, a web-based management and analysis system for patient data of biological products in hospital.

Science.gov (United States)

Lu, Ying-Hao; Kuo, Chen-Chun; Huang, Yaw-Bin

2011-08-01

We selected HTML, PHP and JavaScript as the programming languages to build "WebBio", a web-based system for patient data of biological products and used MySQL as database. WebBio is based on the PHP-MySQL suite and is run by Apache server on Linux machine. WebBio provides the functions of data management, searching function and data analysis for 20 kinds of biological products (plasma expanders, human immunoglobulin and hematological products). There are two particular features in WebBio: (1) pharmacists can rapidly find out whose patients used contaminated products for medication safety, and (2) the statistics charts for a specific product can be automatically generated to reduce pharmacist's work loading. WebBio has successfully turned traditional paper work into web-based data management.

Leveraging a Relationship with Biology to Expand a Relationship with Physics

Science.gov (United States)

Sawtelle, Vashti; Turpen, Chandra

2016-01-01

This work examines how experiences in one disciplinary domain (biology) can impact the relationship a student builds with another domain (physics). We present a model for disciplinary relationships using the constructs of identity, affect, and epistemology. With these constructs we examine an ethnographic case study of a student who experienced a…

Clinical history and biologic age predicted falls better than objective functional tests.

Science.gov (United States)

Gerdhem, Paul; Ringsberg, Karin A M; Akesson, Kristina; Obrant, Karl J

2005-03-01

Fall risk assessment is important because the consequences, such as a fracture, may be devastating. The objective of this study was to find the test or tests that best predicted falls in a population-based sample of elderly women. The fall-predictive ability of a questionnaire, a subjective estimate of biologic age and objective functional tests (gait, balance [Romberg and sway test], thigh muscle strength, and visual acuity) were compared in 984 randomly selected women, all 75 years of age. A recalled fall was the most important predictor for future falls. Only recalled falls and intake of psycho-active drugs independently predicted future falls. Women with at least five of the most important fall predictors (previous falls, conditions affecting the balance, tendency to fall, intake of psychoactive medication, inability to stand on one leg, high biologic age) had an odds ratio of 11.27 (95% confidence interval 4.61-27.60) for a fall (sensitivity 70%, specificity 79%). The more time-consuming objective functional tests were of limited importance for fall prediction. A simple clinical history, the inability to stand on one leg, and a subjective estimate of biologic age were more important as part of the fall risk assessment.

Systems biology in critical-care nursing.

Science.gov (United States)

Schallom, Lynn; Thimmesch, Amanda R; Pierce, Janet D

2011-01-01

Systems biology applies advances in technology and new fields of study including genomics, transcriptomics, proteomics, and metabolomics to the development of new treatments and approaches of care for the critically ill and injured patient. An understanding of systems biology enhances a nurse's ability to implement evidence-based practice and to educate patients and families on novel testing and therapies. Systems biology is an integrated and holistic view of humans in relationship with the environment. Biomarkers are used to measure the presence and severity of disease and are rapidly expanding in systems biology endeavors. A systems biology approach using predictive, preventive, and participatory involvement is being utilized in a plethora of conditions of critical illness and injury including sepsis, cancer, pulmonary disease, and traumatic injuries.

The functional and biological properties of whey proteins: prospects for the development of functional foods

Directory of Open Access Journals (Sweden)

H. J. T. KORHONEN

2008-12-01

Full Text Available Advances in processing technologies and the accumulation of scientific data on the functional and biological properties of whey components have contributed to the growing commercial valuation of cheese whey over the last decade. New membrane separation and chromatographic techniques have made it possible to fractionate and enrich various components of whey more efficiently than before. The specific properties of these components can now be examined in greater detail and new applications developed accordingly. The utilisation of cheese whey is evolving into a new industry producing a multitude of purified ingredients for numerous purposes. The most significant areas of R&D related to whey proteins include functional foods, the rheological properties of foodstuffs, and biopharmaceuticals.

Development of cryogenic free-piston reciprocating expander utilizing phase controller

Energy Technology Data Exchange (ETDEWEB)

Cha, Jeong Min; Park, Ji Ho; Kim, Kyung Joong; Jeong, Sang Kwon [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2016-06-15

A free-piston reciprocating expander is a device which operates without any mechanical linkage to a stationary part. Since the motion of the floating piston is only controlled by the pressure difference at two ends of the piston, this kind of expander may indispensably require a sophisticated active control system equipped with multiple valves and reservoirs. In this paper, we have suggested a novel design that can further reduce complexity of the previously developed cryogenic free-piston expander configuration. It is a simple replacement of both multiple valves and reservoirs by a combination of an orifice valve and a reservoir. The functional characteristic of the integrated orifice-reservoir configuration is similar to that of a phase controller applied in a pulse tube refrigerator so that we designate the one as a phase controller. Depending on the orifice valve size in the phase controller, the different PV work which affects the expander performance is generated. The numerical model of this unique free-piston reciprocating expander utilizing a phase controller is established to understand and analyze quantitatively the performance variation of the expander under different valve timing and orifice valve size. The room temperature experiments are carried out to examine the performance of this newly developed cryogenic expander.

Development of cryogenic free-piston reciprocating expander utilizing phase controller

International Nuclear Information System (INIS)

Cha, Jeong Min; Park, Ji Ho; Kim, Kyung Joong; Jeong, Sang Kwon

2016-01-01

A free-piston reciprocating expander is a device which operates without any mechanical linkage to a stationary part. Since the motion of the floating piston is only controlled by the pressure difference at two ends of the piston, this kind of expander may indispensably require a sophisticated active control system equipped with multiple valves and reservoirs. In this paper, we have suggested a novel design that can further reduce complexity of the previously developed cryogenic free-piston expander configuration. It is a simple replacement of both multiple valves and reservoirs by a combination of an orifice valve and a reservoir. The functional characteristic of the integrated orifice-reservoir configuration is similar to that of a phase controller applied in a pulse tube refrigerator so that we designate the one as a phase controller. Depending on the orifice valve size in the phase controller, the different PV work which affects the expander performance is generated. The numerical model of this unique free-piston reciprocating expander utilizing a phase controller is established to understand and analyze quantitatively the performance variation of the expander under different valve timing and orifice valve size. The room temperature experiments are carried out to examine the performance of this newly developed cryogenic expander

Effect of biological factors during functional scintigraphy of the heart

Energy Technology Data Exchange (ETDEWEB)

Breuel, H P; Emrich, D; Luig, H [Goettingen Univ. (F.R. Germany). Abt. fuer Nuklearmedizin

1976-07-01

The parameters relating to functional scintigraphy of the heart (average circulation time, peak time) depend not only on the method (injection technique, radiopharmaceutical), but also on biological factors. Failure to take these into consideration may result in an erroneous interpretation of the findings. Circulation time in normal children aged 6 to 14 years, as determined by isotope methods is significantly shorter than in normal adults. Patients with compensated heart disease, as well trained athletes, show significant increase in all portions of the circulation time, when compared with normals of similar ages. This indicates that deviation in the haemodynamics of the circulation as shown by functional scintigraphy, can only be interpreted in the light of clinical findings.

Two Dogmas of Biology

Directory of Open Access Journals (Sweden)

Leonore Fleming

2017-01-01

Full Text Available The problem with reductionism in biology is not the reduction, but the implicit attitude of determinism that usually accompanies it. Methodological reductionism is supported by deterministic beliefs, but making such a connection is problematic when it is based on an idea of determinism as fixed predictability. Conflating determinism with predictability gives rise to inaccurate models that overlook the dynamic complexity of our world, as well as ignore our epistemic limitations when we try to model it. Furthermore, the assumption of a strictly deterministic framework is unnecessarily hindering to biology. By removing the dogma of determinism, biological methods, including reductive methods, can be expanded to include stochastic models and probabilistic interpretations. Thus, the dogma of reductionism can be saved once its ties with determinism are severed. In this paper, I analyze two problems that have faced molecular biology for the last 50 years—protein folding and cancer. Both cases demonstrate the long influence of reductionism and determinism on molecular biology, as well as how abandoning determinism has opened the door to more probabilistic and unconstrained reductive methods in biology.

Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.

Science.gov (United States)

Mistretta, Charlotte M; Kumari, Archana

2017-02-10

The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function. Activating or suppressing Hh signaling, with genetic models or pharmacological agents used in cancer treatments, disrupts taste papilla and taste bud integrity and can eliminate responses from taste nerves to chemical stimuli but not to touch or temperature. Understanding Hh regulation of taste organ homeostasis contributes knowledge about the basic biology underlying taste disruptions in patients treated with Hh pathway inhibitors.

PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.

Science.gov (United States)

van Oers, Johanna M M; Roa, Sergio; Werling, Uwe; Liu, Yiyong; Genschel, Jochen; Hou, Harry; Sellers, Rani S; Modrich, Paul; Scharff, Matthew D; Edelmann, Winfried

2010-07-27

The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease activity. To determine the biological functions of this activity in mammals, we generated endonuclease-deficient Pms2E702K knock-in mice. Pms2EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2-/- mice, Pms2EK/EK male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression.

Expanding subjectivities

DEFF Research Database (Denmark)

Lundgaard Andersen, Linda; Soldz, Stephen

2012-01-01

A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool......-Saxon and continental traditions, this special issue provides examples of the use of researcher subjectivity, informed by psychoanalytic thinking, in expanding research understanding....

Functions of MicroRNAs in Cardiovascular Biology and Disease

Science.gov (United States)

Hata, Akiko

2015-01-01

In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology. PMID:23157557

Crucible: A System for Space Synthetic Biology Experiments

Data.gov (United States)

National Aeronautics and Space Administration — The goal of this project is to expand the capability and methodologies in experimental extreme biology as a step towards Martian ecopoiesis. The objectives in...

Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy

Science.gov (United States)

Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J.; Rivière, Isabelle

2009-01-01

Summary Based on promising pre-clinical data demonstrating the eradication of systemic B cell malignancies by CD19-targeted T lymphocytes in vivo in SCID beige mouse models, we are launching Phase 1 clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). We present here the validation of the bioprocess we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads® CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semi-closed culture system using the Wave bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in SCID beige mice bearing disseminated tumors. The validation requirements in terms of T cell expansion, T cell transduction with the 1928z CAR, biological activity, quality control testing and release criteria were met for all four validation runs using apheresis products from patients with CLL. Additionally, following expansion of the T cells, the diversity of the skewed Vβ T cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemo-refractory CLL and in patients with relapsed ALL. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any chimeric antigen receptor or T cell receptor. PMID:19238016

Novel power MOSFET-based expander for high frequency ultrasound systems.

Science.gov (United States)

Choi, Hojong; Shung, K Kirk

2014-01-01

The function of an expander is to obstruct the noise signal transmitted by the pulser so that it does not pass into the transducer or receive electronics, where it can produce undesirable ring-down in an ultrasound imaging application. The most common type is a diode-based expander, which is essentially a simple diode-pair, is widely used in pulse-echo measurements and imaging applications because of its simple architecture. However, diode-based expanders may degrade the performance of ultrasonic transducers and electronic components on the receiving and transmitting sides of the ultrasound systems, respectively. Since they are non-linear devices, they cause excessive signal attenuation and noise at higher frequencies and voltages. In this paper, a new type of expander that utilizes power MOSFET components, which we call a power MOSFET-based expander, is introduced and evaluated for use in high frequency ultrasound imaging systems. The performance of a power MOSFET-based expander was evaluated relative to a diode-based expander by comparing the noise figure (NF), insertion loss (IL), total harmonic distortion (THD), response time (RT), electrical impedance (EI) and dynamic power consumption (DPC). The results showed that the power MOSFET-based expander provided better NF (0.76 dB), IL (-0.3 dB) and THD (-62.9 dB), and faster RT (82 ns) than did the diode-based expander (NF (2.6 dB), IL (-1.4 dB), THD (-56.0 dB) and RT (119 ns)) at 70 MHz. The -6 dB bandwidth and the peak-to-peak voltage of the echo signal received by the transducer using the power MOSFET-based expander improved by 17.4% and 240% compared to the diode-based expander, respectively. The new power MOSFET-based expander was shown to yield lower NF, IL and THD, faster RT and lower ring down than the diode-based expander at the expense of higher dynamic power consumption. Copyright © 2013 Elsevier B.V. All rights reserved.

Using cell structures to develop functional nanomaterials and nanostructures--case studies of actin filaments and microtubules.

Science.gov (United States)

Wu, Kevin Chia-Wen; Yang, Chung-Yao; Cheng, Chao-Min

2014-04-25

This article is based on the continued development of biologically relevant elements (i.e., actin filaments and microtubules in living cells) as building blocks to create functional nanomaterials and nanostructures that can then be used to manufacture nature-inspired small-scale devices or systems. Here, we summarize current progress in the field and focus specifically on processes characterized by (1) robustness and ease of use, (2) inexpensiveness, and (3) potential expandability to mass production. This article, we believe, will provide scientists and engineers with a more comprehensive understanding of how to mine biological materials and natural design features to construct functional materials and devices.

"A mission-driven discipline": the growth of conservation biology.

Science.gov (United States)

Meine, Curt; Soulé, Michael; Noss, Reed E

2006-06-01

Conservation biology emerged in the mid-1980s, drawing on established disciplines and integrating them in pursuit of a coherent goal: the protection and perpetuation of the Earth's biological diversity. Opportunistic in its borrowing and application of knowledge, conservation biology had its roots within the established biological sciences and resource management disciplines but has continually incorporated insights from the empirical experience of resource managers, from the social sciences and humanities, and from diverse cultural sources. The Society for Conservation Biology (SCB) has represented the field's core constituency, while expanding that constituency in keeping with the field's integrative spirit. Conservation Biology has served as SCB's flagship publication, promoting research, dialog, debate, and application of the field's essential concepts. Over the last 20 years the field, SCB, and the journal have evolved to meet changing conservation needs, to explore gaps in our knowledge base, to incorporate new information from related fields, to build professional capacity, and to provide expanded opportunities for international participation. In turn, the field, SCB, and journal have prompted change in related fields, organizations, and publications. In its dedication to advancing the scientific foundations of biodiversity conservation and placing that science at the service of society in a world whose variety, wildness, and beauty we care for conservation biology represents both a continuation and radical reconfiguration of the traditional relationship between science and conservation.

Conservation Biology and Traditional Ecological Knowledge: Integrating Academic Disciplines for Better Conservation Practice

Directory of Open Access Journals (Sweden)

Joshua A. Drew

2006-12-01

Full Text Available Conservation biology and environmental anthropology are disciplines that are both concerned with the identification and preservation of diversity, in one case biological and in the other cultural. Both conservation biology and the study of traditional ecoloigcal knowledge function at the nexus of the social and natural worlds, yet historically there have been major impediments to integrating the two. Here we identify linguistic, cultural, and epistemological barriers between the two disciplines. We argue that the two disciplines are uniquely positioned to inform each other and to provide critical insights and new perspectives on the way these sciences are practiced. We conclude by synthesizing common themes found in conservation success stories, and by making several suggestions on integration. These include cross-disciplinary publication, expanding memberships in professional societies and conducting multidisciplinary research based on similar interests in ecological process, taxonomy, or geography. Finally, we argue that extinction threats, be they biological or cultural/linguistic are imminent, and that by bringing these disciplines together we may be able to forge synergistic conservation programs capable of protecting the vivid splendor of life on Earth.

Frontiers of NMR in Molecular Biology

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-08-25

NMR spectroscopy is expanding the horizons of structural biology by determining the structures and describing the dynamics of blobular proteins in aqueous solution, as well as other classes of proteins including membrane proteins and the polypeptides that form the aggregates diagnostic of prion and amyloid diseases. Significant results are also emerging on DNA and RNA oligomers and their complexes with proteins. This meeting focused attention on key structural questions emanating from molecular biology and how NMR spectroscopy can be used to answer them.

Removal design report for the 108-F Biological Laboratory

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-09-01

Most of the 100-F facilities were deactivated with the reactor and have since been demolished. Of the dozen or so reactor-related structures, only the 105-F Reactor Building and the 108-F Biology Laboratory remain standing today. The 108-F Biology Laboratory was intended to be used as a facility for the mixing and addition of chemicals used in the treatment of the reactor cooling water. Shortly after F Reactor began operation, it was determined that the facility was not needed for this purpose. In 1949, the building was converted for use as a biological laboratory. In 1962, the lab was expanded by adding a three-story annex to the original four-story structure. The resulting lab had a floor area of approximately 2,883 m{sup 2} (main building and annex) that operated until 1973. The building contained 47 laboratories, a number of small offices, a conference room, administrative section, lunch and locker rooms, and a heavily shielded, high-energy exposure cell. The purpose of this removal design report is to establish the methods of decontamination and decommissioning and the supporting functions associated with facility removal and disposal.

Removal design report for the 108-F Biological Laboratory

International Nuclear Information System (INIS)

1997-09-01

Most of the 100-F facilities were deactivated with the reactor and have since been demolished. Of the dozen or so reactor-related structures, only the 105-F Reactor Building and the 108-F Biology Laboratory remain standing today. The 108-F Biology Laboratory was intended to be used as a facility for the mixing and addition of chemicals used in the treatment of the reactor cooling water. Shortly after F Reactor began operation, it was determined that the facility was not needed for this purpose. In 1949, the building was converted for use as a biological laboratory. In 1962, the lab was expanded by adding a three-story annex to the original four-story structure. The resulting lab had a floor area of approximately 2,883 m 2 (main building and annex) that operated until 1973. The building contained 47 laboratories, a number of small offices, a conference room, administrative section, lunch and locker rooms, and a heavily shielded, high-energy exposure cell. The purpose of this removal design report is to establish the methods of decontamination and decommissioning and the supporting functions associated with facility removal and disposal

A Gaussian mixture model based cost function for parameter estimation of chaotic biological systems

Science.gov (United States)

Shekofteh, Yasser; Jafari, Sajad; Sprott, Julien Clinton; Hashemi Golpayegani, S. Mohammad Reza; Almasganj, Farshad

2015-02-01

As we know, many biological systems such as neurons or the heart can exhibit chaotic behavior. Conventional methods for parameter estimation in models of these systems have some limitations caused by sensitivity to initial conditions. In this paper, a novel cost function is proposed to overcome those limitations by building a statistical model on the distribution of the real system attractor in state space. This cost function is defined by the use of a likelihood score in a Gaussian mixture model (GMM) which is fitted to the observed attractor generated by the real system. Using that learned GMM, a similarity score can be defined by the computed likelihood score of the model time series. We have applied the proposed method to the parameter estimation of two important biological systems, a neuron and a cardiac pacemaker, which show chaotic behavior. Some simulated experiments are given to verify the usefulness of the proposed approach in clean and noisy conditions. The results show the adequacy of the proposed cost function.

Molecular biology and its applications in orthodontics and oral and maxillofacial surgery

NARCIS (Netherlands)

Ren, Yjin

2005-01-01

: Molecular biology is an exciting, rapidly expanding field, which has enabled enormously greater understanding of the biology of diseases and malfunctions in many fields. It chiefly concerns itself with understanding the interactions between the various systems of a cell, including the

Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

Science.gov (United States)

Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica; Buch-Månson, Nina; Bovet, Nicolas; Nygård, Jesper; Martinez, Karen L; Meldal, Morten

2016-01-11

Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biophysics and systems biology.

Science.gov (United States)

Noble, Denis

2010-03-13

Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. Their approach has since been extended to other organs of the body, notably including the heart. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights.

Expanding Thurston maps

CERN Document Server

Bonk, Mario

2017-01-01

This monograph is devoted to the study of the dynamics of expanding Thurston maps under iteration. A Thurston map is a branched covering map on a two-dimensional topological sphere such that each critical point of the map has a finite orbit under iteration. It is called expanding if, roughly speaking, preimages of a fine open cover of the underlying sphere under iterates of the map become finer and finer as the order of the iterate increases. Every expanding Thurston map gives rise to a fractal space, called its visual sphere. Many dynamical properties of the map are encoded in the geometry of this visual sphere. For example, an expanding Thurston map is topologically conjugate to a rational map if and only if its visual sphere is quasisymmetrically equivalent to the Riemann sphere. This relation between dynamics and fractal geometry is the main focus for the investigations in this work.

Functional mining of transporters using synthetic selections

DEFF Research Database (Denmark)

Genee, Hans Jasper; Bali, Anne Pihl; Petersen, Søren Dalsgård

2016-01-01

transporters, PnuT, which is widely distributed across multiple bacterial phyla. We demonstrate that with modular replacement of the biosensor, we could expand our method to xanthine and identify xanthine permeases from gut and soil metagenomes. Our results demonstrate how synthetic-biology approaches can......-responsive biosensor systems that enable selective growth of cells only if they encode a ligand-specific importer. We developed such a synthetic selection system for thiamine pyrophosphate and mined soil and gut metagenomes for thiamine-uptake functions. We identified several members of a novel class of thiamine...

Integrating cell biology and proteomic approaches in plants.

Science.gov (United States)

Takáč, Tomáš; Šamajová, Olga; Šamaj, Jozef

2017-10-03

Significant improvements of protein extraction, separation, mass spectrometry and bioinformatics nurtured advancements of proteomics during the past years. The usefulness of proteomics in the investigation of biological problems can be enhanced by integration with other experimental methods from cell biology, genetics, biochemistry, pharmacology, molecular biology and other omics approaches including transcriptomics and metabolomics. This review aims to summarize current trends integrating cell biology and proteomics in plant science. Cell biology approaches are most frequently used in proteomic studies investigating subcellular and developmental proteomes, however, they were also employed in proteomic studies exploring abiotic and biotic stress responses, vesicular transport, cytoskeleton and protein posttranslational modifications. They are used either for detailed cellular or ultrastructural characterization of the object subjected to proteomic study, validation of proteomic results or to expand proteomic data. In this respect, a broad spectrum of methods is employed to support proteomic studies including ultrastructural electron microscopy studies, histochemical staining, immunochemical localization, in vivo imaging of fluorescently tagged proteins and visualization of protein-protein interactions. Thus, cell biological observations on fixed or living cell compartments, cells, tissues and organs are feasible, and in some cases fundamental for the validation and complementation of proteomic data. Validation of proteomic data by independent experimental methods requires development of new complementary approaches. Benefits of cell biology methods and techniques are not sufficiently highlighted in current proteomic studies. This encouraged us to review most popular cell biology methods used in proteomic studies and to evaluate their relevance and potential for proteomic data validation and enrichment of purely proteomic analyses. We also provide examples of

Good Manufacturing Practice-Compliant Production and Lot-Release of Ex Vivo Expanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders

Directory of Open Access Journals (Sweden)

Manuel Wiesinger

2017-10-01

Full Text Available In recent years, the exploration of regulatory T cell (Treg-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore, ex vivo expansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer. Here, we present a protocol for the GMP-compliant production, lot-release and validation of ex vivo expanded Tregs for treatment of patients with autoimmune and inflammatory disorders. In the presented production protocol, large numbers of Treg, previously enriched from a leukapheresis product by using the CliniMACS® system, are ex vivo expanded in the presence of anti-CD3/anti-CD28 expander beads, exogenous IL-2 and rapamycin during 21 days. The expanded Treg drug product passed predefined lot-release criteria. These criteria include (i sterility testing, (ii assessment of Treg phenotype, (iii assessment of non-Treg cellular impurities, (iv confirmation of successful anti-CD3/anti-CD28 expander bead removal after expansion, and (v confirmation of the biological function of the Treg product. Furthermore, the Treg drug product was shown to retain its stability and suppressive function for at least 1 year after freezing and thawing. Also, dilution of the Treg drug product in 0.9% physiological saline did not affect Treg phenotype and Treg function for up to 90 min. These data indicate that these cells are ready to use in a clinical setting in which a cell infusion time of up to 90 min can be expected. The presented production process has recently undergone on site GMP-conform evaluation and received GMP certification from the Bavarian authorities in Germany. This protocol can now be used for Treg-based therapy of various

Synthetic biology and its promises

Directory of Open Access Journals (Sweden)

José Manuel De Cózar Escalante

2016-12-01

Full Text Available Synthetic biology is a new science and emerging technology, or rather a technoscience, which converges with others such as nanotechnology, information technology, robotics, artificial intelligence and neuroscience. All have common features that could have highly concerning social and environmental impacts. With its ambitious goals of controlling complexity, redesigning and creating new living entities, synthetic biology perfectly exemplifies the new bioeconomic reality. This requires expanding the focus of the discussion beyond the limited comparative analysis of risks and benefits, to address uncertainties, reassign responsibilities and initiate a thorough social assessment of what is at stake.

[The hyperiricosuria as an indicator of derangement of biologic functions of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension].

Science.gov (United States)

Titov, V N; Oshchepkova, E V; Dmitriev, V A; Gushchina, O V; Shiriaeva, Iu K; Iashin, A Ia

2012-04-01

During millions years in all animals allantoine (oxidized by uricase uric acid) was catabolite of purines and ascorbic acid was an acceptor of active forms of oxygen. The proximal tubules of nephron reabsorbed the trace amounts of uric acid Then during phylogenesis the primates had a mutation of ascorbic acid gen minus. Later on occurred a second spontaneous mutation and uricase gen minus and uric acid became catabolites of purines. In absence of ascorbic acid synthesis ions of urates became a major capturers of active forms of oxygen and all uric acid as before underwent the reabsorption. Later the carriers were formed which began in epithelium of proximal tubules to secrete all uric acid into urine. At every incident of "littering" of intercellular medium with endogenic flogogens (impairment of biologic function of endoecology) under compensatory development of biologic reaction of inflammation the need in inactivation of active forms of oxygen increases. Hence later on in phylogenesis one more stage was formed--post secretory reabsorption of uric acid In the biologic reaction of inflammation epithelium of proximal tubules initiates retentional hyperiricosuria. The general antioxidant activity of human blood plasma in 60% is presented by urates' ions. The excretion of uric acid includes 4 stages: filtration, full reabsorption, secretion and post secretory reabsorption. In phylogenesis these stages formed in sequence. The mild hyperiricosuria is most frequently considered as a non-specific indicator of activation of biologic reaction of inflammation. The productive hyperiricosuria develops more infrequently under surplus of meat food and cytolysis syndrome (intensification of cell loss in vivo). Under concentration of uric acid more than 400 mkmol/l part of urates circulates in intercellular medium in the form of crystals. The microcrystals of uric acid (biologic "litter") initiate the syndrome of systemic inflammatory response as an endogenic flogogen

Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

Directory of Open Access Journals (Sweden)

Mathieu Angin

Full Text Available While modulation of regulatory T cell (Treg function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region, characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.

FUNCTION IN BIOLOGY: ETIOLOGICAL AND ORGANIZATIONAL PERSPECTIVES

Directory of Open Access Journals (Sweden)

Charbel Niño El-Hani

2009-10-01

Full Text Available ABSTRACT. In this paper, we argue for a taxonomy of approaches to function based on different epistemological perspectives assumed with regard to the treatment of this central concept in the life sciences. We distinguish between etiological and organizational perspectives on function, analyzing two distinct theories related to each perspective: Wright’s selectionist etiological approach and Godfrey-Smith’s modern history theory of functions, in the case of the etiological perspective; and Cummins’ functional analysis and Collier’s interactivist approach to function, among organizational accounts. We explain differences and similarities between these theories and the broader perspectives on function, arguing for a particular way of understanding the consensus without unity in debates about function. While explaining the accounts of function, we also deal with the relationship between this concept and other important biological concepts, such as adaptation, selection, complexity, and autonomy. We also advance an argument for the limits and prospects of the explanatory role of function in evolution. By arguing that changes in functionality are always grounded on changes in systems’ organization, we show that function can never explain the origins of traits. Nevertheless, it can explain the spread of traits in populations, but only when we are dealing with functionally novel traits. Finally, we stress that organizational accounts of function are needed to understand how new functions appear by means of changes in systems’ organization. KEYWORDS: Function; Teleology; Explanation; Etiology; Organization.   RESUMEN. En este artículo, argumentamos a favor de una taxonomía de abordajes sobre función basada en diferentes perspectivas epistemológicas a cerca del tratamiento de este concepto central en las ciencias de la vida. Distinguimos entre perspectivas etiológicas y organizacionales sobre función, analizando dos teorías distintas

Comparison of self-expandable and balloon-expanding stents for hybrid ductal stenting in hypoplastic left heart complex.

Science.gov (United States)

Goreczny, Sebastian; Qureshi, Shakeel A; Rosenthal, Eric; Krasemann, Thomas; Nassar, Mohamed S; Anderson, David R; Morgan, Gareth J

2017-07-01

We aimed to compare the procedural and mid-term performance of a specifically designed self-expanding stent with balloon-expandable stents in patients undergoing hybrid palliation for hypoplastic left heart syndrome and its variants. The lack of specifically designed stents has led to off-label use of coronary, biliary, or peripheral stents in the neonatal ductus arteriosus. Recently, a self-expanding stent, specifically designed for use in hypoplastic left heart syndrome, has become available. We carried out a retrospective cohort comparison of 69 neonates who underwent hybrid ductal stenting with balloon-expandable and self-expanding stents from December, 2005 to July, 2014. In total, 43 balloon-expandable stents were implanted in 41 neonates and more recently 47 self-expanding stents in 28 neonates. In the balloon-expandable stents group, stent-related complications occurred in nine patients (22%), compared with one patient in the self-expanding stent group (4%). During follow-up, percutaneous re-intervention related to the ductal stent was performed in five patients (17%) in the balloon-expandable stent group and seven patients (28%) in self-expanding stents group. Hybrid ductal stenting with self-expanding stents produced favourable results when compared with the results obtained with balloon-expandable stents. Immediate additional interventions and follow-up re-interventions were similar in both groups with complications more common in those with balloon-expandable stents.

Gravitational Clustering of Galaxies in an Expanding Universe ...

Indian Academy of Sciences (India)

2006-12-08

Dec 8, 2006 ... Abstract. We inquire the phenomena of clustering of galaxies in an expanding universe from a theoretical point of view on the basis of ther- modynamics and correlation functions. The partial differential equation is developed both for the point mass and extended mass structures of a two-point correlation ...

Enzymes for ecdysteroid biosynthesis: their biological functions in insects and beyond.

Science.gov (United States)

Niwa, Ryusuke; Niwa, Yuko S

2014-01-01

Steroid hormones are responsible for the coordinated regulation of many aspects of biological processes in multicellular organisms. Since the last century, many studies have identified and characterized steroidogenic enzymes in vertebrates, including mammals. However, much less is known about invertebrate steroidogenic enzymes. In the last 15 years, a number of steroidogenic enzymes and their functions have been characterized in ecdysozoan animals, especially in the fruit fly Drosophila melanogaster. In this review, we summarize the latest knowledge of enzymes crucial for synthesizing ecdysteroids, the principal insect steroid hormones. We also discuss the functional conservation and diversity of ecdysteroidogenic enzymes in other insects and even non-insect species, such as nematodes, vertebrates, and lower eukaryotes.

The functional biology and trophic role of krill (Thysanoessa raschii) in a Greenlandic fjord

DEFF Research Database (Denmark)

Agersted, Mette Dalgaard; Nielsen, Torkel Gissel; Munk, Peter

2011-01-01

Despite being a key zooplankton group, knowledge on krill biology from the Arctic is inadequate. The present study examine the functional biology and evaluate the trophic role of krill in the GodthAyenbsfjord (64 degrees N, 51 degrees W) SW Greenland, through a combination of fieldwork...... and laboratory experiments. Krill biomass was highest in the middle fjord and inner fjord, whereas no krill was found offshore. The dominating species Thysanoessa raschii revealed a type III functional response when fed with the diatom Thalassiosira weissflogii. At food saturation, T. raschii exhibited a daily...... ration of 1% body C d(-1). Furthermore, T. raschii was capable of exploiting plankton cells from 5 to 400 mu m, covering several trophic levels of the pelagic food web. The calculated grazing impact by T. raschii on the fjord plankton community was negligible. However, the schooling and migratory...

PreproVIP-derived peptides in the human female genital tract: expression and biological function

DEFF Research Database (Denmark)

Bredkjoer, H E; Palle, C; Ekblad, E

1997-01-01

The aim of the study was to elucidate the localization, distribution, colocalization and biological effect of preproVIP-derived peptides in the human female genital tract. Radioimmunoassays applying antisera against the five functional domains of the VIP precursor in combination with immunohistoc......The aim of the study was to elucidate the localization, distribution, colocalization and biological effect of preproVIP-derived peptides in the human female genital tract. Radioimmunoassays applying antisera against the five functional domains of the VIP precursor in combination...... with immunohistochemistry were used. The effect of preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170 on genital smooth muscle activity in the Fallopian tube was investigated in vitro and compared to that of VIP. All the preproVIP-derived peptides were expressed throughout the genital tract in neuronal elements...

Linking biological soil crust diversity to ecological functions

Science.gov (United States)

Glaser, Karin; Borchhardt, Nadine; Schulz, Karoline; Mikhailyuk, Tatiana; Baumann, Karen; Leinweber, Peter; Ulf, Karsten

2016-04-01

Biological soil crusts (BSCs) are an association of different microorganisms and soil particles in the top millimeters of the soil. They are formed by algae, cyanobacteria, microfungi, bacteria, bryophytes and lichens in various compositions. Our aim was to determine and compare the biodiversity of all occurring organisms in biogeographically different habitats, ranging from polar (both Arctic and Antarctic), subpolar (Scandinavia), temperate (Germany) to dry regions (Chile). The combination of microscopy and molecular techniques (next-generation sequencing) revealed highly diverse crust communities, whose composition clustered by region and correlates with habitat characteristics such as water content. The BSC biodiversity was then linked to the ecological function of the crusts. The functional role of the BSCs in the biogeochemical cycles of carbon, nitrogen and phosphorous is evaluated using an array of state of the art soil chemistry methods including Py-FIMS (pyrolysis field ionization mass spectrometry) and XANES (x-ray absorbance near edge structure). Total P as well as P fractions were quantified in all BSCs, adjacent soil underneath and comparable nearby soil of BSC-free areas revealing a remarkable accumulation of total phosphorous and a distinct pattern of P fractions in the crust. Further, we observed an indication of a different P-speciation composition in the crust compared with BSC-free soil. The data allow answering the question whether BSCs act as sink or source for these compounds, and how biodiversity controls the biogeochemical function of BSCs.

A Bayesian spatial model for neuroimaging data based on biologically informed basis functions.

Science.gov (United States)

Huertas, Ismael; Oldehinkel, Marianne; van Oort, Erik S B; Garcia-Solis, David; Mir, Pablo; Beckmann, Christian F; Marquand, Andre F

2017-11-01

The dominant approach to neuroimaging data analysis employs the voxel as the unit of computation. While convenient, voxels lack biological meaning and their size is arbitrarily determined by the resolution of the image. Here, we propose a multivariate spatial model in which neuroimaging data are characterised as a linearly weighted combination of multiscale basis functions which map onto underlying brain nuclei or networks or nuclei. In this model, the elementary building blocks are derived to reflect the functional anatomy of the brain during the resting state. This model is estimated using a Bayesian framework which accurately quantifies uncertainty and automatically finds the most accurate and parsimonious combination of basis functions describing the data. We demonstrate the utility of this framework by predicting quantitative SPECT images of striatal dopamine function and we compare a variety of basis sets including generic isotropic functions, anatomical representations of the striatum derived from structural MRI, and two different soft functional parcellations of the striatum derived from resting-state fMRI (rfMRI). We found that a combination of ∼50 multiscale functional basis functions accurately represented the striatal dopamine activity, and that functional basis functions derived from an advanced parcellation technique known as Instantaneous Connectivity Parcellation (ICP) provided the most parsimonious models of dopamine function. Importantly, functional basis functions derived from resting fMRI were more accurate than both structural and generic basis sets in representing dopamine function in the striatum for a fixed model order. We demonstrate the translational validity of our framework by constructing classification models for discriminating parkinsonian disorders and their subtypes. Here, we show that ICP approach is the only basis set that performs well across all comparisons and performs better overall than the classical voxel-based approach

Two Types of Expanding Lie Algebra and New Expanding Integrable Systems

International Nuclear Information System (INIS)

Dong Huanhe; Yang Jiming; Wang Hui

2010-01-01

From a new Lie algebra proposed by Zhang, two expanding Lie algebras and its corresponding loop algebras are obtained. Two expanding integrable systems are produced with the help of the generalized zero curvature equation. One of them has complex Hamiltion structure with the help of generalized Tu formula (GTM). (general)

Synthetic biology approaches to fluorinated polyketides.

Science.gov (United States)

Thuronyi, Benjamin W; Chang, Michelle C Y

2015-03-17

The catalytic diversity of living systems offers a broad range of opportunities for developing new methods to produce small molecule targets such as fuels, materials, and pharmaceuticals. In addition to providing cost-effective and renewable methods for large-scale commercial processes, the exploration of the unusual chemical phenotypes found in living organisms can also enable the expansion of chemical space for discovery of novel function by combining orthogonal attributes from both synthetic and biological chemistry. In this context, we have focused on the development of new fluorine chemistry using synthetic biology approaches. While fluorine has become an important feature in compounds of synthetic origin, the scope of biological fluorine chemistry in living systems is limited, with fewer than 20 organofluorine natural products identified to date. In order to expand the diversity of biosynthetically accessible organofluorines, we have begun to develop methods for the site-selective introduction of fluorine into complex natural products by engineering biosynthetic machinery to incorporate fluorinated building blocks. To gain insight into how both enzyme active sites and metabolic pathways can be evolved to manage and select for fluorinated compounds, we have studied one of the only characterized natural hosts for organofluorine biosynthesis, the soil microbe Streptomyces cattleya. This information provides a template for designing engineered organofluorine enzymes, pathways, and hosts and has allowed us to initiate construction of enzymatic and cellular pathways for the production of fluorinated polyketides.

Biological effects of simple changes in functionality on rhodium metalloinsertors

Science.gov (United States)

Weidmann, Alyson G.; Komor, Alexis C.; Barton, Jacqueline K.

2013-01-01

DNA mismatch repair (MMR) is crucial to ensuring the fidelity of the genome. The inability to correct single base mismatches leads to elevated mutation rates and carcinogenesis. Using metalloinsertors–bulky metal complexes that bind with high specificity to mismatched sites in the DNA duplex–our laboratory has adopted a new chemotherapeutic strategy through the selective targeting of MMR-deficient cells, that is, those that have a propensity for cancerous transformation. Rhodium metalloinsertors display inhibitory effects selectively in cells that are deficient in the MMR machinery, consistent with this strategy. However, a highly sensitive structure–function relationship is emerging with the development of new complexes that highlights the importance of subcellular localization. We have found that small structural modifications, for example a hydroxyl versus a methyl functional group, can yield profound differences in biological function. Despite similar binding affinities and selectivities for DNA mismatches, only one metalloinsertor shows selective inhibition of cellular proliferation in MMR-deficient versus -proficient cells. Studies of whole-cell, nuclear and mitochondrial uptake reveal that this selectivity depends upon targeting DNA mismatches in the cell nucleus. PMID:23776288

Structure, function, and behaviour of computational models in systems biology.

Science.gov (United States)

Knüpfer, Christian; Beckstein, Clemens; Dittrich, Peter; Le Novère, Nicolas

2013-05-31

Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such "bio-models" necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models themselves are represented precisely in terms of mathematical expressions their full meaning is not yet formally specified and only described in natural language. We present a conceptual framework - the meaning facets - which can be used to rigorously specify the semantics of bio-models. A bio-model has a dual interpretation: On the one hand it is a mathematical expression which can be used in computational simulations (intrinsic meaning). On the other hand the model is related to the biological reality (extrinsic meaning). We show that in both cases this interpretation should be performed from three perspectives: the meaning of the model's components (structure), the meaning of the model's intended use (function), and the meaning of the model's dynamics (behaviour). In order to demonstrate the strengths of the meaning facets framework we apply it to two semantically related models of the cell cycle. Thereby, we make use of existing approaches for computer representation of bio-models as much as possible and sketch the missing pieces. The meaning facets framework provides a systematic in-depth approach to the semantics of bio-models. It can serve two important purposes: First, it specifies and structures the information which biologists have to take into account if they build, use and exchange models. Secondly, because it can be formalised, the framework is a solid foundation for any sort of computer support in bio-modelling. The proposed conceptual framework establishes a new methodology for modelling in Systems Biology and constitutes a basis for computer-aided collaborative research.

Space Biology in the 21st century

Science.gov (United States)

Halstead, Thora W.; Krauss, Robert W.

1990-01-01

Space Biology is poised to make significant contributions to science in the next century. A carefully crafted, but largely ground-based, program in the United States has evolved major questions that require answers through experiments in space. Science, scientists, and the new long-term spacecrafts designed by NASA will be available for the first time to mount a serious Space Biology effort. The scientific challenge is of such importance that success will provide countless benefits to biologically dependent areas such as medicine, food, and commerce in the decades ahead. The international community is rapidly expanding its role in this field. The United States should generate the resources that will allow progress in Space Biology to match the recognized progress made in aeronautics and the other space sciences.

Dissipation and fluctuation of quantum fields in expanding universes

International Nuclear Information System (INIS)

Morikawa, M.

1990-01-01

A stochastic dynamics of a long-wavelength part of a scalar field in an expanding universe is derived by using the influence functional method. Dissipation as well as fluctuation are derived for general parameters: a mass, a coupling to the scalar curvature, and a cutoff scale parameter. A dissipation-fluctuation relation is found with a temperature which is proportional to the Hawking temperature, but system dependent. The method is further applied to an expanding universe with a power law and yields the dispersion which agrees with that obtained by the regularization method. The back reaction to the background de Sitter space itself is also obtained

TCA Cycle and Mitochondrial Membrane Potential Are Necessary for Diverse Biological Functions.

Science.gov (United States)

Martínez-Reyes, Inmaculada; Diebold, Lauren P; Kong, Hyewon; Schieber, Michael; Huang, He; Hensley, Christopher T; Mehta, Manan M; Wang, Tianyuan; Santos, Janine H; Woychik, Richard; Dufour, Eric; Spelbrink, Johannes N; Weinberg, Samuel E; Zhao, Yingming; DeBerardinis, Ralph J; Chandel, Navdeep S

2016-01-21

Mitochondrial metabolism is necessary for the maintenance of oxidative TCA cycle function and mitochondrial membrane potential. Previous attempts to decipher whether mitochondria are necessary for biological outcomes have been hampered by genetic and pharmacologic methods that simultaneously disrupt multiple functions linked to mitochondrial metabolism. Here, we report that inducible depletion of mitochondrial DNA (ρ(ο) cells) diminished respiration, oxidative TCA cycle function, and the mitochondrial membrane potential, resulting in diminished cell proliferation, hypoxic activation of HIF-1, and specific histone acetylation marks. Genetic reconstitution only of the oxidative TCA cycle function specifically in these inducible ρ(ο) cells restored metabolites, resulting in re-establishment of histone acetylation. In contrast, genetic reconstitution of the mitochondrial membrane potential restored ROS, which were necessary for hypoxic activation of HIF-1 and cell proliferation. These results indicate that distinct mitochondrial functions associated with respiration are necessary for cell proliferation, epigenetics, and HIF-1 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

Expanding the genetic heterogeneity of intellectual disability

KAUST Repository

Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T.; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E.; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M.; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M.; Alkuraya, Hisham; Salih, Mustafa A.; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W.; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T.; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S.

2017-01-01

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

Expanding the genetic heterogeneity of intellectual disability

KAUST Repository

Anazi, Shams

2017-09-22

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

Expanding the genetic heterogeneity of intellectual disability.

Science.gov (United States)

Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M; Alkuraya, Hisham; Salih, Mustafa A; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S

2017-11-01

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

Rapid evolution of parasite life history traits on an expanding range-edge.

Science.gov (United States)

Kelehear, Crystal; Brown, Gregory P; Shine, Richard

2012-04-01

Parasites of invading species undergoing range advance may be exposed to powerful new selective forces. Low host density in range-edge populations hampers parasite transmission, requiring the parasite to survive longer periods in the external environment before encountering a potential host. These conditions should favour evolutionary shifts in offspring size to maximise parasite transmission. We conducted a common-garden experiment to compare life history traits among seven populations of the nematode lungworm (Rhabdias pseudosphaerocephala) spanning from the parasite population core to the expanding range-edge in invasive cane toads (Rhinella marina) in tropical Australia. Compared to conspecifics from the population core, nematodes from the range-edge exhibited larger eggs, larger free-living adults and larger infective larvae, and reduced age at maturity in parasitic adults. These results support a priori predictions regarding adaptive changes in offspring size as a function of invasion history, and suggest that parasite life history traits can evolve rapidly in response to the selective forces exerted by a biological invasion. © 2012 Blackwell Publishing Ltd/CNRS.

IAEA biological reference materials

International Nuclear Information System (INIS)

Parr, R.M.; Schelenz, R.; Ballestra, S.

1988-01-01

The Analytical Quality Control Services programme of the IAEA encompasses a wide variety of intercomparisons and reference materials. This paper reviews only those aspects of the subject having to do with biological reference materials. The 1988 programme foresees 13 new intercomparison exercises, one for major, minor and trace elements, five for radionuclides, and seven for stable isotopes. Twenty-two natural matrix biological reference materials are available: twelve for major, minor and trace elements, six for radionuclides, and four for chlorinated hydrocarbons. Seven new intercomparisons and reference materials are in preparation or under active consideration. Guidelines on the correct use of reference materials are being prepared for publication in 1989 in consultation with other major international producers and users of biological reference materials. The IAEA database on available reference materials is being updated and expanded in scope, and a new publication is planned for 1989. (orig.)

A Few Integrable Dynamical Systems, Recurrence Operators, Expanding Integrable Models and Hamiltonian Structures by the r -Matrix Method

International Nuclear Information System (INIS)

Zhang Yu-Feng; Muhammad, Iqbal; Yue Chao

2017-01-01

We extend two known dynamical systems obtained by Blaszak, et al. via choosing Casimir functions and utilizing Novikov–Lax equation so that a series of novel dynamical systems including generalized Burgers dynamical system, heat equation, and so on, are followed to be generated. Then we expand some differential operators presented in the paper to deduce two types of expanding dynamical models. By taking the generalized Burgers dynamical system as an example, we deform its expanding model to get a half-expanding system, whose recurrence operator is derived from Lax representation, and its Hamiltonian structure is also obtained by adopting a new way. Finally, we expand the generalized Burgers dynamical system to the (2+1)-dimensional case whose Hamiltonian structure is derived by Poisson tensor and gradient of the Casimir function. Besides, a kind of (2+1)-dimensional expanding dynamical model of the (2+1)-dimensional dynamical system is generated as well. (paper)

Evaluated Rayleigh integrals for pulsed planar expanding ring sources

International Nuclear Information System (INIS)

Warshaw, S.I.

1985-01-01

Time-domain analytic and semianalytic pressure fields acoustically radiated from expanding pulsed ring sources imbedded in a planar rigid baffle have been calculated. The source functions are radially symmetric delta-function distributions whose amplitude and argument have simple functional dependencies on radius and time. Certain cases yield closed analytic results, while others result in elliptic integrals, which are evaluated to high accuracy by Gauss-Chebyshev and modified Gauss-Legendre quadrature. These results are of value for calibrating computer simulations and convolution procedures, and estimating fields from more complex planar radiators. 3 refs., 4 figs

Development of an Instrument for Measuring Self-Efficacy in Cell Biology

Science.gov (United States)

Reeve, Suzanne; Kitchen, Elizabeth; Sudweeks, Richard R.; Bell, John D.; Bradshaw, William S.

2011-01-01

This article describes the development of a ten-item scale to assess biology majors' self-efficacy towards the critical thinking and data analysis skills taught in an upper-division cell biology course. The original seven-item scale was expanded to include three additional items based on the results of item analysis. Evidence of reliability and…

Role of soil biology and soil functions in relation to land use intensity.

Science.gov (United States)

Bondi, Giulia; Wall, David; Bacher, Matthias; Emmet-Booth, Jeremy; Graça, Jessica; Marongiu, Irene; Creamer, Rachel

2017-04-01

The delivery of the ecosystem's functions is predominantly controlled by soil biology. The biology found in a gram of soil contains more than ten thousand individual species of bacteria and fungi (Torsvik et al., 1990). Understanding the role and the requirements of these organisms is essential for the protection and the sustainable use of soils. Soil biology represents the engine of all the processes occurring in the soil and it supports the ecosystem services such as: 1) nutrient mineralisation 2) plant production 3) water purification and regulation and 4) carbon cycling and storage. During the last years land management type and intensity have been identified as major drivers for microbial performance in soil. For this reason land management needs to be appropriately studied to understand the role of soil biology within this complex interplay of functions. We aimed to study whether and how land management drives soil biological processes and related functions. To reach this objective we built a land use intensity index (LUI) able to quantify the impact of the common farming practices carried out in Irish grassland soils. The LUI is derived from a detailed farmer questionnaire on grassland management practices at 38 farms distributed in the five major agro-climatic regions of Ireland defined by Holden and Brereton (2004). Soils were classified based on their drainage status according to the Irish Soil Information System by Creamer et al. (2014). This detailed questionnaire is then summarised into 3 management intensity components: (i) intensity of Fertilisation (Fi), (ii) frequency of Mowing (Mi) and (iii) intensity of Livestock Grazing (Gi). Sites were sampled to assess the impact of land management intensity on microbial community structure and enzyme behaviour in relation to nitrogen, phosphorus and carbon cycling. Preliminary results for enzymes linked to C and N cycles showed higher activity in relation to low grazing pressure (low Gi). Enzymes linked to P

Microstructure, mechanical properties, and biological response to functionally graded HA coatings

International Nuclear Information System (INIS)

Rabiei, Afsaneh; Blalock, Travis; Thomas, Brent; Cuomo, Jerry; Yang, Y.; Ong, Joo

2007-01-01

Hydroxyapatite (HA) [Ca 10 (PO 4 ) 6 (OH) 2 ] is the primary mineral content, representing 43% by weight, of bone. Applying a thin layer of HA, to the surface of a metal implant, can promote osseointegration and increase the mechanical stability of the implant. In this study, a biocompatible coating comprising an HA film with functionally graded crystallinity is being deposited on a heated substrate in an Ion Beam Assisted Deposition (IBAD) system. The microstructure of the film was studied using Transmission Electron Microscopy techniques. Finally, initial cell adhesion and cell differentiation on the coating was evaluated using ATCC CRL 1486 human embryonic palatal mesenchymal cell, an osteoblast precursor cell line. The results have shown superior mechanical properties and biological response to the functionally graded HA film

Expander for Thin-Wall Tubing

Science.gov (United States)

Pessin, R.

1983-01-01

Tool locally expands small-diameter tubes. Tube expander locally expands and deforms tube: Compressive lateral stress induced in elastomeric sleeve by squeezing axially between two metal tool parts. Adaptable to situations in which tube must have small bulge for mechanical support or flow control.

The Widespread Prevalence and Functional Significance of Silk-Like Structural Proteins in Metazoan Biological Materials.

Directory of Open Access Journals (Sweden)

Carmel McDougall

Full Text Available In nature, numerous mechanisms have evolved by which organisms fabricate biological structures with an impressive array of physical characteristics. Some examples of metazoan biological materials include the highly elastic byssal threads by which bivalves attach themselves to rocks, biomineralized structures that form the skeletons of various animals, and spider silks that are renowned for their exceptional strength and elasticity. The remarkable properties of silks, which are perhaps the best studied biological materials, are the result of the highly repetitive, modular, and biased amino acid composition of the proteins that compose them. Interestingly, similar levels of modularity/repetitiveness and similar bias in amino acid compositions have been reported in proteins that are components of structural materials in other organisms, however the exact nature and extent of this similarity, and its functional and evolutionary relevance, is unknown. Here, we investigate this similarity and use sequence features common to silks and other known structural proteins to develop a bioinformatics-based method to identify similar proteins from large-scale transcriptome and whole-genome datasets. We show that a large number of proteins identified using this method have roles in biological material formation throughout the animal kingdom. Despite the similarity in sequence characteristics, most of the silk-like structural proteins (SLSPs identified in this study appear to have evolved independently and are restricted to a particular animal lineage. Although the exact function of many of these SLSPs is unknown, the apparent independent evolution of proteins with similar sequence characteristics in divergent lineages suggests that these features are important for the assembly of biological materials. The identification of these characteristics enable the generation of testable hypotheses regarding the mechanisms by which these proteins assemble and direct the

In Vitro Comparison of Self-Expanding Versus Balloon-Expandable Stents in a Human Ex Vivo Model

International Nuclear Information System (INIS)

Grenacher, Lars; Rohde, Stefan; Gaenger, Ellen; Deutsch, Jochen; Kauffmann, Guenter W.; Richter, Goetz M.

2006-01-01

The objective was to compare the radial strength and expansile precision of self-expanding stents and balloon-expandable stents in a human cadaver bifurcation model. Seven different self-expanding (LUMINEXX, JOSTENT SelfX, JOSTENT SelfX hrf, Sinus-Repo, Sinus SuperFlex, Easy Wallstent, SMART) and four different balloon-expandable stent models (Palmaz, Sinus Stent, SAXX Medium, JOSTENT peripheral), each type 10 stents (total n = 110 stents) were implanted into the common iliac arteries of human cadaver corpses. The maximum stent diameter was 10 mm for all models. After stent implantation, the specimens were filled with silicone caoutchouc. After 24 h, the vascular walls including the stents were removed from the hardened casts. Diameters were taken and the weight of the cast cylinders was measured in air and in purified water to calculate the volume of the bodies (according to Archimedes Law) as a relative but precise degree for the radial strength of the implanted stents. The cylindrical casts of the self-expanding stents showed lower mean diameters (8.2 ± 1.0 mm) and mean volumes (0.60 ± 0.14 ml/cm) than in the balloon-expandable stent group (10.1 ± 0.3 mm and 0.71 ± 0.04 ml/cm, respectively; p < 0.01). The nominal maximum diameter of 10 mm was not achieved in any of the self-expanding stents, but this was achieved in more than 70% (29/40) of the balloon-expandable stent specimens (p < 0.05). The variation between achieved volumes was significantly larger in self-expanding (range: 0.23-0.78 ml/cm) than in balloon-expandable stents (range: 0.66-0.81 ml/cm; p < 0.05). Self-expanding stents presented considerably lower radial expansion force and lower degree of precision than balloon-expandable stents

The Structure and Function of Biological Networks

Science.gov (United States)

Wu, Daniel Duanqing

2010-01-01

Biology has been revolutionized in recent years by an explosion in the availability of data. Transforming this new wealth of data into meaningful biological insights and clinical breakthroughs requires a complete overhaul both in the questions being asked and the methodologies used to answer them. A major challenge in organizing and understanding…

Pectin: cell biology and prospects for functional analysis.

Science.gov (United States)

Willats, W G; McCartney, L; Mackie, W; Knox, J P

2001-09-01

Pectin is a major component of primary cell walls of all land plants and encompasses a range of galacturonic acid-rich polysaccharides. Three major pectic polysaccharides (homogalacturonan, rhamnogalacturonan-I and rhamnogalacturonan-II) are thought to occur in all primary cell walls. This review surveys what is known about the structure and function of these pectin domains. The high degree of structural complexity and heterogeneity of the pectic matrix is produced both during biosynthesis in the endomembrane system and as a result of the action of an array of wall-based pectin-modifying enzymes. Recent developments in analytical techniques and in the generation of anti-pectin probes have begun to place the structural complexity of pectin in cell biological and developmental contexts. The in muro de-methyl-esterification of homogalacturonan by pectin methyl esterases is emerging as a key process for the local modulation of matrix properties. Rhamnogalacturonan-I comprises a highly diverse population of spatially and developmentally regulated polymers, whereas rhamnogalacturonan-II appears to be a highly conserved and stable pectic domain. Current knowledge of biosynthetic enzymes, plant and microbial pectinases and the interactions of pectin with other cell wall components and the impact of molecular genetic approaches are reviewed in terms of the functional analysis of pectic polysaccharides in plant growth and development.

3S - Systematic, systemic, and systems biology and toxicology.

Science.gov (United States)

Smirnova, Lena; Kleinstreuer, Nicole; Corvi, Raffaella; Levchenko, Andre; Fitzpatrick, Suzanne C; Hartung, Thomas

2018-01-01

A biological system is more than the sum of its parts - it accomplishes many functions via synergy. Deconstructing the system down to the molecular mechanism level necessitates the complement of reconstructing functions on all levels, i.e., in our conceptualization of biology and its perturbations, our experimental models and computer modelling. Toxicology contains the somewhat arbitrary subclass "systemic toxicities"; however, there is no relevant toxic insult or general disease that is not systemic. At least inflammation and repair are involved that require coordinated signaling mechanisms across the organism. However, the more body components involved, the greater the challenge to reca-pitulate such toxicities using non-animal models. Here, the shortcomings of current systemic testing and the development of alternative approaches are summarized. We argue that we need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modelling these systems using bioengineering and virtual computer models, i.e., via systems biology or systems toxicology approaches. Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities, i.e., the perturbation on organism level, without using substitute organisms (animals). The next challenge is to establish disease models, i.e., micropathophysiological systems (MPPS), to expand their utility to encompass biomedicine. Combining computational and experimental systems approaches and the chal-lenges of validating them are discussed. The suggested 3S approach promises to leverage 21st century technology and systematic thinking to achieve a paradigm change in studying systemic effects.

Biological adaptations for functional features of language in the face of cultural evolution.

Science.gov (United States)

Christiansen, Morten H; Reali, Florencia; Chater, Nick

2011-04-01

Although there may be no true language universals, it is nonetheless possible to discern several family resemblance patterns across the languages of the world. Recent work on the cultural evolution of language indicates the source of these patterns is unlikely to be an innate universal grammar evolved through biological adaptations for arbitrary linguistic features. Instead, it has been suggested that the patterns of resemblance emerge because language has been shaped by the brain, with individual languages representing different but partially overlapping solutions to the same set of nonlinguistic constraints. Here, we use computational simulations to investigate whether biological adaptation for functional features of language, deriving from cognitive and communicative constraints, may nonetheless be possible alongside rapid cultural evolution. Specifically, we focus on the Baldwin effect as an evolutionary mechanism by which previously learned linguistic features might become innate through natural selection across many generations of language users. The results indicate that cultural evolution of language does not necessarily prevent functional features of language from becoming genetically fixed, thus potentially providing a particularly informative source of constraints on cross-linguistic resemblance patterns.

General method to find the attractors of discrete dynamic models of biological systems

Science.gov (United States)

Gan, Xiao; Albert, Réka

2018-04-01

Analyzing the long-term behaviors (attractors) of dynamic models of biological networks can provide valuable insight. We propose a general method that can find the attractors of multilevel discrete dynamical systems by extending a method that finds the attractors of a Boolean network model. The previous method is based on finding stable motifs, subgraphs whose nodes' states can stabilize on their own. We extend the framework from binary states to any finite discrete levels by creating a virtual node for each level of a multilevel node, and describing each virtual node with a quasi-Boolean function. We then create an expanded representation of the multilevel network, find multilevel stable motifs and oscillating motifs, and identify attractors by successive network reduction. In this way, we find both fixed point attractors and complex attractors. We implemented an algorithm, which we test and validate on representative synthetic networks and on published multilevel models of biological networks. Despite its primary motivation to analyze biological networks, our motif-based method is general and can be applied to any finite discrete dynamical system.

General method to find the attractors of discrete dynamic models of biological systems.

Science.gov (United States)

Gan, Xiao; Albert, Réka

2018-04-01

Analyzing the long-term behaviors (attractors) of dynamic models of biological networks can provide valuable insight. We propose a general method that can find the attractors of multilevel discrete dynamical systems by extending a method that finds the attractors of a Boolean network model. The previous method is based on finding stable motifs, subgraphs whose nodes' states can stabilize on their own. We extend the framework from binary states to any finite discrete levels by creating a virtual node for each level of a multilevel node, and describing each virtual node with a quasi-Boolean function. We then create an expanded representation of the multilevel network, find multilevel stable motifs and oscillating motifs, and identify attractors by successive network reduction. In this way, we find both fixed point attractors and complex attractors. We implemented an algorithm, which we test and validate on representative synthetic networks and on published multilevel models of biological networks. Despite its primary motivation to analyze biological networks, our motif-based method is general and can be applied to any finite discrete dynamical system.

BioCore Guide: A Tool for Interpreting the Core Concepts of Vision and Change for Biology Majors

Science.gov (United States)

Freeman, Scott; Wenderoth, Mary Pat; Crowe, Alison J.

2014-01-01

Vision and Change in Undergraduate Biology Education outlined five core concepts intended to guide undergraduate biology education: 1) evolution; 2) structure and function; 3) information flow, exchange, and storage; 4) pathways and transformations of energy and matter; and 5) systems. We have taken these general recommendations and created a Vision and Change BioCore Guide—a set of general principles and specific statements that expand upon the core concepts, creating a framework that biology departments can use to align with the goals of Vision and Change. We used a grassroots approach to generate the BioCore Guide, beginning with faculty ideas as the basis for an iterative process that incorporated feedback from more than 240 biologists and biology educators at a diverse range of academic institutions throughout the United States. The final validation step in this process demonstrated strong national consensus, with more than 90% of respondents agreeing with the importance and scientific accuracy of the statements. It is our hope that the BioCore Guide will serve as an agent of change for biology departments as we move toward transforming undergraduate biology education. PMID:26086653

An expandable prosthesis with dual cage-and-plate function in a single device for vertebral body replacement: the clinical experience on 14 consecutive cases with vertebral tumors.

Science.gov (United States)

Ramírez, J J; Ramírez, J J; Chiquete, E; Gómez-Limón, E

2011-09-01

The aim of this paper was to test the hypothesis that an expandable prosthesis with dual cage-and-plate function can provide immediate and durable spine stabilization after corpectomy. We designed an expandable vertebral body prosthesis with dual cage-and-plate function in a single device (JR-prosthesis). Anatomical studies were performed to design a titanium-made prosthesis. Cadaver assays were done with a stainless steal device to test fixation and adequacy to the human spine anatomy. Then, 14 patients with vertebral tumors (8 metastatic) underwent corpectomy and vertebral body replacement with the JR-prosthesis. All patients had neurological deficit, severe pain and spine instability (mean follow-up: 25.4 months). Mean pain score before surgery in a visual analog scale improved from 7.6 to 3.0 points after operation (P=0.002). All patients achieved at least one grade of improvement in the Frankel score (P=0.003), excepting the 3 patients with Frankel grade A presurgery. Two patients with renal cell carcinoma died during the following 4 days after surgery (renal failure and massive bleeding), the rest attained a painless and stable spine immediately and maintained for long periods. No significant infections or implant failures were registered. A non-fatal case of inferior vena cava surgical injury was observed (repaired during surgery without further complications). The JR-prosthesis stabilizes the spine immediately after surgery and for the rest of the patients' life. To our knowledge, this is the first report on the clinical experience of any expandable vertebral body prosthesis with dual cage-and-plate function in a single device. These observations await confirmation in different scenarios.

Heterocyclic Naphthalimides as New Skeleton Structure of Compounds with Increasingly Expanding Relational Medicinal Applications.

Science.gov (United States)

Gong, Huo-Hui; Addla, Dinesh; Lv, Jing-Song; Zhou, Cheng-He

2016-01-01

Naphthalimide compounds are an important type of nitrogen-containing aromatic heterocycles with cyclic double imides and the naphthalene framework. This π-deficient large conjugated planar structure enables naphthalimide derivatives to readily interact with various biological cations, anions, small molecules and macromolecules such as DNAs, enzymes and recetors in living organism via noncovalent bonds, therefore exhibiting extensive potentiality in relatively medicinal applications. Currently, some naphthalimides as anticancer agents have entered into clinical trials and other naphthalimide-based medicinal developments as potential drugs for treatment of various diseases are actively and unprecedentedly expanding. Naphthalimide-derived artificial ion receptors, fluorescent probes and cell imaging agents are being overwhelmingly investigated and have a diversity of potential applications in real-time detecting ions and biomolecules, understanding biological processes and determining pharmacological and pharmacokinetic properties. All the above mentions have strongly implied that naphthalimide-based derivatives as new skeleton structure of compounds possess increasingly expanding relational medicinal applications, and the related research is becoming a quite attractive active topic and newly rising highlight. Combining with our research and referring other works from literature, this work systematically reviews the current research and development of heterocyclic naphthalimides as anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antidepressant agents as well as artificial cation and anion receptors, diagnostic agents and pathologic probes, and cell imaging agents for biologically important species. Some rational design strategies, structure-activity relationships and action mechanisms are discussed. The perspectives of the future development of naphthalimide-based medicinal chemistry are also presented.

Importance of N-Glycosylation on CD147 for Its Biological Functions

Science.gov (United States)

Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian-Li; Chen, Zhi-Nan

2014-01-01

Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation. PMID:24739808

Importance of N-Glycosylation on CD147 for Its Biological Functions

Directory of Open Access Journals (Sweden)

Yang Bai

2014-04-01

Full Text Available Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

AR42J-B-13 cell: An expandable progenitor to generate an unlimited supply of functional hepatocytes

International Nuclear Information System (INIS)

Wallace, Karen; Fairhall, Emma A.; Charlton, Keith A.; Wright, Matthew C.

2010-01-01

Hepatocytes are the preparation of choice for Toxicological research in vitro. However, despite the fact that hepatocytes proliferate in vivo during liver regeneration, they are resistant to proliferation in vitro, do not tolerate sub-culture and tend to enter a de-differentiation program that results in a loss of hepatic function. These limitations have resulted in the search for expandable rodent and human cells capable of being directed to differentiate into functional hepatocytes. Research with stem cells suggests that it may be possible to provide the research community with hepatocytes in vitro although to date, significant challenges remain, notably generating a sufficiently pure population of hepatocytes with a quantitative functionality comparable with hepatocytes. This paper reviews work with the AR42J-B-13 (B-13) cell line. The B-13 cell was cloned from the rodent AR42J pancreatic cell line, express genes associated with pancreatic acinar cells and readily proliferates in simple culture media. When exposed to glucocorticoid, 75-85% of the cells trans-differentiate into hepatocyte-like (B-13/H) cells functioning at a level quantitatively similar to freshly isolated rat hepatocytes (with the remaining cells retaining the B-13 phenotype). Trans-differentiation of pancreatic acinar cells also appears to occur in vivo in rats treated with glucocorticoid; in mice with elevated circulating glucocorticoid and in humans treated for long periods with glucocorticoid. The B-13 response to glucocorticoid therefore appears to be related to a real pathophysiological response of a pancreatic cell to glucocorticoid. An understanding of how this process occurs and if it can be generated or engineered in human cells would result in a cell line with the ability to generate an unlimited supply of functional human hepatocytes in a cost effective manner.

Functionalized gold nanoparticle supported sensory mechanisms applied in detection of chemical and biological threat agents: A review

International Nuclear Information System (INIS)

Upadhyayula, Venkata K.K.

2012-01-01

Highlights: ► Smart sensors are needed for detection of chemical and biological threat agents. ► Smart sensors detect analytes with rapid speed, high sensitivity and selectivity. ► Functionalized gold nanoparticles (GNPs) can potentially smart sense threat agents. ► Functionalized GNPs support multiple analytical methods for sensing threat agents. ► Threat agents of all types can be detected using functionalized GNPs. - Abstract: There is a great necessity for development of novel sensory concepts supportive of smart sensing capabilities in defense and homeland security applications for detection of chemical and biological threat agents. A smart sensor is a detection device that can exhibit important features such as speed, sensitivity, selectivity, portability, and more importantly, simplicity in identifying a target analyte. Emerging nanomaterial based sensors, particularly those developed by utilizing functionalized gold nanoparticles (GNPs) as a sensing component potentially offer many desirable features needed for threat agent detection. The sensitiveness of physical properties expressed by GNPs, e.g. color, surface plasmon resonance, electrical conductivity and binding affinity are significantly enhanced when they are subjected to functionalization with an appropriate metal, organic or biomolecular functional groups. This sensitive nature of functionalized GNPs can be potentially exploited in the design of threat agent detection devices with smart sensing capabilities. In the presence of a target analyte (i.e., a chemical or biological threat agent) a change proportional to concentration of the analyte is observed, which can be measured either by colorimetric, fluorimetric, electrochemical or spectroscopic means. This article provides a review of how functionally modified gold colloids are applied in the detection of a broad range of threat agents, including radioactive substances, explosive compounds, chemical warfare agents, biotoxins, and

Functionalized gold nanoparticle supported sensory mechanisms applied in detection of chemical and biological threat agents: A review

Energy Technology Data Exchange (ETDEWEB)

Upadhyayula, Venkata K.K., E-mail: Upadhyayula.Venkata@epa.gov [Oak Ridge Institute of Science and Education (ORISE), MC-100-44, PO Box 117, Oak Ridge, TN 37831 (United States)

2012-02-17

Highlights: Black-Right-Pointing-Pointer Smart sensors are needed for detection of chemical and biological threat agents. Black-Right-Pointing-Pointer Smart sensors detect analytes with rapid speed, high sensitivity and selectivity. Black-Right-Pointing-Pointer Functionalized gold nanoparticles (GNPs) can potentially smart sense threat agents. Black-Right-Pointing-Pointer Functionalized GNPs support multiple analytical methods for sensing threat agents. Black-Right-Pointing-Pointer Threat agents of all types can be detected using functionalized GNPs. - Abstract: There is a great necessity for development of novel sensory concepts supportive of smart sensing capabilities in defense and homeland security applications for detection of chemical and biological threat agents. A smart sensor is a detection device that can exhibit important features such as speed, sensitivity, selectivity, portability, and more importantly, simplicity in identifying a target analyte. Emerging nanomaterial based sensors, particularly those developed by utilizing functionalized gold nanoparticles (GNPs) as a sensing component potentially offer many desirable features needed for threat agent detection. The sensitiveness of physical properties expressed by GNPs, e.g. color, surface plasmon resonance, electrical conductivity and binding affinity are significantly enhanced when they are subjected to functionalization with an appropriate metal, organic or biomolecular functional groups. This sensitive nature of functionalized GNPs can be potentially exploited in the design of threat agent detection devices with smart sensing capabilities. In the presence of a target analyte (i.e., a chemical or biological threat agent) a change proportional to concentration of the analyte is observed, which can be measured either by colorimetric, fluorimetric, electrochemical or spectroscopic means. This article provides a review of how functionally modified gold colloids are applied in the detection of a broad

Biological response to purification and acid functionalization of carbon nanotubes

Science.gov (United States)

Figarol, Agathe; Pourchez, Jérémie; Boudard, Delphine; Forest, Valérie; Tulliani, Jean-Marc; Lecompte, Jean-Pierre; Cottier, Michèle; Bernache-Assollant, Didier; Grosseau, Philippe

2014-07-01

Acid functionalization has been considered as an easy way to enhance the dispersion and biodegradation of carbon nanotubes (CNT). However, inconsistencies between toxicity studies of acid functionalized CNT remain unexplained. This could be due to a joint effect of the main physicochemical modifications resulting from an acid functionalization: addition of surface acid groups and purification from catalytic metallic impurities. In this study, the impact on CNT biotoxicity of these two physiochemical features was assessed separately. The in vitro biological response of RAW 264.7 macrophages was evaluated after exposure to 15-240 µg mL-1 of two types of multi-walled CNT. For each type of CNT (small: 20 nm diameter, and big: 90 nm diameter), three different surface chemical properties were studied (total of six CNT samples): pristine, acid functionalized and desorbed. Desorbed CNT were purified by the acid functionalization but presented a very low amount of surface acid groups due to a thermal treatment under vacuum. A Janus effect of acid functionalization with two opposite impacts is highlighted. The CNT purification decreased the overall toxicity, while the surface acid groups intensified it when present at a specific threshold. These acid groups especially amplified the pro-inflammatory response. The threshold mechanism which seemed to regulate the impact of acid groups should be further studied to determine its value and potential link to the other physicochemical state of the CNT. The results suggest that, for a safer-design approach, the benefit-risk balance of an acid functionalization has to be considered, depending on the CNT primary state of purification. Further research should be conducted in this direction.

STAT6: its role in interleukin 4-mediated biological functions.

Science.gov (United States)

Takeda, K; Kishimoto, T; Akira, S

1997-05-01

Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

Steric restrictions of RISC in RNA interference identified with size-expanded RNA nucleobases.

Science.gov (United States)

Hernández, Armando R; Peterson, Larryn W; Kool, Eric T

2012-08-17

Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modified siRNAs have been reported, relatively few studies with modified nucleobases exist. Here we describe the synthesis and hybridization properties of siRNAs bearing size-expanded RNA (xRNA) nucleobases and their use as a novel and systematic set of steric probes in RNAi. xRNA nucleobases are expanded by 2.4 Å using benzo-homologation and retain canonical Watson-Crick base-pairing groups. Our data show that the modified siRNA duplexes display small changes in melting temperature (+1.4 to -5.0 °C); substitutions near the center are somewhat destabilizing to the RNA duplex, while substitutions near the ends are stabilizing. RNAi studies in a dual-reporter luciferase assay in HeLa cells revealed that xRNA nucleobases in the antisense strand reduce activity at some central positions near the seed region but are generally well tolerated near the ends. Most importantly, we observed that xRNA substitutions near the 3'-end increased activity over that of wild-type siRNAs. The data are analyzed in terms of site-dependent steric effects in RISC. Circular dichroism experiments show that single xRNA substitutions do not significantly distort the native A-form helical structure of the siRNA duplex, and serum stability studies demonstrated that xRNA substitutions protect siRNAs against nuclease degradation.

Microbial Biofilms and Breast Tissue Expanders

Directory of Open Access Journals (Sweden)

Melissa J. Karau

2013-01-01

Full Text Available We previously developed and validated a vortexing-sonication technique for detection of biofilm bacteria on the surface of explanted prosthetic joints. Herein, we evaluated this technique for diagnosis of infected breast tissue expanders and used it to assess colonization of breast tissue expanders. From April 2008 to December 2011, we studied 328 breast tissue expanders at Mayo Clinic, Rochester, MN, USA. Of seven clinically infected breast tissue expanders, six (85.7% had positive cultures, one of which grew Propionibacterium species. Fifty-two of 321 breast tissue expanders (16.2%, 95% CI, 12.3–20.7% without clinical evidence of infection also had positive cultures, 45 growing Propionibacterium species and ten coagulase-negative staphylococci. While vortexing-sonication can detect clinically infected breast tissue expanders, 16 percent of breast tissue expanders appear to be asymptomatically colonized with normal skin flora, most commonly, Propionibacterium species.

The functionality of biological knowledge in the workplace. Integrating school and workplace learning about reproduction

NARCIS (Netherlands)

Mazereeuw, M.

2013-01-01

This thesis reports on a design research project about a learning, supervising and teaching strategy to enable students in agricultural preparatory vocational secondary education (VMBO) to recognize the functionality of biological knowledge of reproduction in work placement sites. Although

Synthetic biology to access and expand nature’s chemical diversity

Science.gov (United States)

Smanski, Michael J.; Zhou, Hui; Claesen, Jan; Shen, Ben; Fischbach, Michael; Voigt, Christopher A.

2016-01-01

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Economically accessing the potential encoded within sequenced genomes promises to reinvigorate waning drug discovery pipelines and provide novel routes to intricate chemicals. This is a tremendous undertaking, as the pathways often comprise dozens of genes spanning as much as 100+ kiliobases of DNA, are controlled by complex regulatory networks, and the most interesting molecules are made by non-model organisms. Advances in synthetic biology address these issues, including DNA construction technologies, genetic parts for precision expression control, synthetic regulatory circuits, computer aided design, and multiplexed genome engineering. Collectively, these technologies are moving towards an era when chemicals can be accessed en mass based on sequence information alone. This will enable the harnessing of metagenomic data and massive strain banks for high-throughput molecular discovery and, ultimately, the ability to forward design pathways to complex chemicals not found in nature. PMID:26876034

Data Transformation Functions for Expanded Search Spaces in Geographic Sample Supervised Segment Generation

OpenAIRE

Christoff Fourie; Elisabeth Schoepfer

2014-01-01

Sample supervised image analysis, in particular sample supervised segment generation, shows promise as a methodological avenue applicable within Geographic Object-Based Image Analysis (GEOBIA). Segmentation is acknowledged as a constituent component within typically expansive image analysis processes. A general extension to the basic formulation of an empirical discrepancy measure directed segmentation algorithm parameter tuning approach is proposed. An expanded search landscape is defined, c...

Growing functional modules from a seed protein via integration of protein interaction and gene expression data

Directory of Open Access Journals (Sweden)

Dimitrakopoulou Konstantina

2007-10-01

Full Text Available Abstract Background Nowadays modern biology aims at unravelling the strands of complex biological structures such as the protein-protein interaction (PPI networks. A key concept in the organization of PPI networks is the existence of dense subnetworks (functional modules in them. In recent approaches clustering algorithms were applied at these networks and the resulting subnetworks were evaluated by estimating the coverage of well-established protein complexes they contained. However, most of these algorithms elaborate on an unweighted graph structure which in turn fails to elevate those interactions that would contribute to the construction of biologically more valid and coherent functional modules. Results In the current study, we present a method that corroborates the integration of protein interaction and microarray data via the discovery of biologically valid functional modules. Initially the gene expression information is overlaid as weights onto the PPI network and the enriched PPI graph allows us to exploit its topological aspects, while simultaneously highlights enhanced functional association in specific pairs of proteins. Then we present an algorithm that unveils the functional modules of the weighted graph by expanding a kernel protein set, which originates from a given 'seed' protein used as starting-point. Conclusion The integrated data and the concept of our approach provide reliable functional modules. We give proofs based on yeast data that our method manages to give accurate results in terms both of structural coherency, as well as functional consistency.

Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology.

Science.gov (United States)

Sudhir, Putty-Reddy; Chen, Chung-Hsuan

2016-03-22

A protein complex consists of two or more proteins that are linked together through protein-protein interactions. The proteins show stable/transient and direct/indirect interactions within the protein complex or between the protein complexes. Protein complexes are involved in regulation of most of the cellular processes and molecular functions. The delineation of protein complexes is important to expand our knowledge on proteins functional roles in physiological and pathological conditions. The genetic yeast-2-hybrid method has been extensively used to characterize protein-protein interactions. Alternatively, a biochemical-based affinity purification coupled with mass spectrometry (AP-MS) approach has been widely used to characterize the protein complexes. In the AP-MS method, a protein complex of a target protein of interest is purified using a specific antibody or an affinity tag (e.g., DYKDDDDK peptide (FLAG) and polyhistidine (His)) and is subsequently analyzed by means of MS. Tandem affinity purification, a two-step purification system, coupled with MS has been widely used mainly to reduce the contaminants. We review here a general principle for AP-MS-based characterization of protein complexes and we explore several protein complexes identified in pluripotent stem cell biology and cancer biology as examples.

Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

Science.gov (United States)

Wagner, James M; Alper, Hal S

2016-04-01

Coupling the tools of synthetic biology with traditional molecular genetic techniques can enable the rapid prototyping and optimization of yeast strains. While the era of yeast synthetic biology began in the well-characterized model organism Saccharomyces cerevisiae, it is swiftly expanding to include non-conventional yeast production systems such as Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. These yeasts already have roles in the manufacture of vaccines, therapeutic proteins, food additives, and biorenewable chemicals, but recent synthetic biology advances have the potential to greatly expand and diversify their impact on biotechnology. In this review, we summarize the development of synthetic biological tools (including promoters and terminators) and enabling molecular genetics approaches that have been applied in these four promising alternative biomanufacturing platforms. An emphasis is placed on synthetic parts and genome editing tools. Finally, we discuss examples of synthetic tools developed in other organisms that can be adapted or optimized for these hosts in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering.

Science.gov (United States)

Marcucio, Ralph S; Qin, Ling; Alsberg, Eben; Boerckel, Joel D

2017-11-01

The fields of developmental biology and tissue engineering have been revolutionized in recent years by technological advancements, expanded understanding, and biomaterials design, leading to the emerging paradigm of "developmental" or "biomimetic" tissue engineering. While developmental biology and tissue engineering have long overlapping histories, the fields have largely diverged in recent years at the same time that crosstalk opportunities for mutual benefit are more salient than ever. In this perspective article, we will use musculoskeletal development and tissue engineering as a platform on which to discuss these emerging crosstalk opportunities and will present our opinions on the bright future of these overlapping spheres of influence. The multicellular programs that control musculoskeletal development are rapidly becoming clarified, represented by shifting paradigms in our understanding of cellular function, identity, and lineage specification during development. Simultaneously, advancements in bioartificial matrices that replicate the biochemical, microstructural, and mechanical properties of developing tissues present new tools and approaches for recapitulating development in tissue engineering. Here, we introduce concepts and experimental approaches in musculoskeletal developmental biology and biomaterials design and discuss applications in tissue engineering as well as opportunities for tissue engineering approaches to inform our understanding of fundamental biology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2356-2368, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Phase-preserving beam expander for biomedical X-ray imaging

International Nuclear Information System (INIS)

Martinson, Mercedes; Samadi, Nazanin; Bassey, Bassey; Gomez, Ariel; Chapman, Dean

2015-01-01

Building on previous work, a phase-preserving bent Laue beam-expanding monochromator was developed with the capability of performing live animal phase contrast dynamic imaging at the Biomedical Imaging and Therapy beamline at the Canadian Light Source. The BioMedical Imaging and Therapy beamlines at the Canadian Light Source are used by many researchers to capture phase-based imaging data. These experiments have so far been limited by the small vertical beam size, requiring vertical scanning of biological samples in order to image their full vertical extent. Previous work has been carried out to develop a bent Laue beam-expanding monochromator for use at these beamlines. However, the first attempts exhibited significant distortion in the diffraction plane, increasing the beam divergence and eliminating the usefulness of the monochromator for phase-related imaging techniques. Recent work has been carried out to more carefully match the polychromatic and geometric focal lengths in a so-called ‘magic condition’ that preserves the divergence of the beam and enables full-field phase-based imaging techniques. The new experimental parameters, namely asymmetry and Bragg angles, were evaluated by analysing knife-edge and in-line phase images to determine the effect on beam divergence in both vertical and horizontal directions, using the flat Bragg double-crystal monochromator at the beamline as a baseline. The results show that by using the magic condition, the difference between the two monochromator types is less than 10% in the diffraction plane. Phase fringes visible in test images of a biological sample demonstrate that this difference is small enough to enable in-line phase imaging, despite operating at a sub-optimal energy for the wafer and asymmetry angle that was used

Antibiotic resistance shaping multi-level population biology of bacteria.

Science.gov (United States)

Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

2013-01-01

Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

Structure and function in biology

International Nuclear Information System (INIS)

Hirs, C.H.W.

1976-01-01

A summary is given of the history of the developments of structural chemistry in biology beginning with the work of the bacteriologist Ehrlich leading to a comprehensive examination of the influence of size and configuration on the interaction between specific antibodies and side-chain determinants. Recent developments include the recognition of a higher order of specificity in the interaction of proteins with one another

Extending and expanding the Darwinian synthesis: the role of complex systems dynamics.

Science.gov (United States)

Weber, Bruce H

2011-03-01

Darwinism is defined here as an evolving research tradition based upon the concepts of natural selection acting upon heritable variation articulated via background assumptions about systems dynamics. Darwin's theory of evolution was developed within a context of the background assumptions of Newtonian systems dynamics. The Modern Evolutionary Synthesis, or neo-Darwinism, successfully joined Darwinian selection and Mendelian genetics by developing population genetics informed by background assumptions of Boltzmannian systems dynamics. Currently the Darwinian Research Tradition is changing as it incorporates new information and ideas from molecular biology, paleontology, developmental biology, and systems ecology. This putative expanded and extended synthesis is most perspicuously deployed using background assumptions from complex systems dynamics. Such attempts seek to not only broaden the range of phenomena encompassed by the Darwinian Research Tradition, such as neutral molecular evolution, punctuated equilibrium, as well as developmental biology, and systems ecology more generally, but to also address issues of the emergence of evolutionary novelties as well as of life itself. Copyright © 2010 Elsevier Ltd. All rights reserved.

The expanding universe of mass analyzer configurations for biological analysis.

Science.gov (United States)

Calvete, Juan J

2014-01-01

Mass spectrometry (MS) is an analytical technique that measures the mass-to-charge ratio of electrically charged gas-phase particles. All mass spectrometers combine ion formation, mass analysis, and ion detection. Although mass analyzers can be regarded as sophisticated devices that manipulate ions in space and time, the rich diversity of possible ways to combine ion separation, focusing, and detection in dynamic mass spectrometers accounts for the large number of instrument designs. A historical perspective of the progress in mass spectrometry that since 1965 until today have contributed to position this technique as an indispensable tool for biological research has been recently addressed by a privileged witness of this golden age of MS (Gelpí J. Mass Spectrom 43:419-435, 2008; Gelpí J. Mass Spectrom 44:1137-1161, 2008). The aim of this chapter is to highlight the view that the operational principles of mass spectrometry can be understood by a simple mathematical language, and that an understanding of the basic concepts of mass spectrometry is necessary to take the most out of this versatile technique.

Silicon microfabricated beam expander

Science.gov (United States)

Othman, A.; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A.; Ain, M. F.

2015-03-01

The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

Bigelow Expandable Activity Module Project

Data.gov (United States)

National Aeronautics and Space Administration — The Bigelow Expandable Activity Module (BEAM) project is a NASA-industry partnership with Bigelow Aerospace (BA) that has developing the first human-rated expandable...

Functional connectomics from a "big data" perspective.

Science.gov (United States)

Xia, Mingrui; He, Yong

2017-10-15

In the last decade, explosive growth regarding functional connectome studies has been observed. Accumulating knowledge has significantly contributed to our understanding of the brain's functional network architectures in health and disease. With the development of innovative neuroimaging techniques, the establishment of large brain datasets and the increasing accumulation of published findings, functional connectomic research has begun to move into the era of "big data", which generates unprecedented opportunities for discovery in brain science and simultaneously encounters various challenging issues, such as data acquisition, management and analyses. Big data on the functional connectome exhibits several critical features: high spatial and/or temporal precision, large sample sizes, long-term recording of brain activity, multidimensional biological variables (e.g., imaging, genetic, demographic, cognitive and clinic) and/or vast quantities of existing findings. We review studies regarding functional connectomics from a big data perspective, with a focus on recent methodological advances in state-of-the-art image acquisition (e.g., multiband imaging), analysis approaches and statistical strategies (e.g., graph theoretical analysis, dynamic network analysis, independent component analysis, multivariate pattern analysis and machine learning), as well as reliability and reproducibility validations. We highlight the novel findings in the application of functional connectomic big data to the exploration of the biological mechanisms of cognitive functions, normal development and aging and of neurological and psychiatric disorders. We advocate the urgent need to expand efforts directed at the methodological challenges and discuss the direction of applications in this field. Copyright © 2017 Elsevier Inc. All rights reserved.

Late-stage diversification of biologically active pyridazinones via a direct C-H functionalization strategy.

Science.gov (United States)

Li, Wei; Fan, Zhoulong; Geng, Kaijun; Xu, Youjun; Zhang, Ao

2015-01-14

Divergent C-H functionalization reactions (arylation, carboxylation, olefination, thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone moiety as an internal directing group were successfully established. This approach offers a late-stage, ortho-selective diversification of a biologically active pyridazinone scaffold. Seven series of novel pyridazinone analogues were synthesized conveniently as the synthetic precursors of potential sortase A (SrtA) inhibitors.

Helium turbo-expander with an alternator

International Nuclear Information System (INIS)

Akiyama, Yoshitane

1980-01-01

Study was made on a helium turbo-expander, the heart of helium refrigerator systems, in order to develop a system which satisfies the required conditions. A helium turbo-expander with externally pressurized helium gas bearings at the temperature of liquid nitrogen and an alternator as a brake have been employed. The essential difference between a helium turbo-expander and a nitrogen turbo-expander was clarified. The gas bearing lubricated with nitrogen at room temperature and the gas bearing lubricated with helium at low temperature were tested. The flow rate of helium in a helium refrigerator for a large superconducting magnet is comparatively small, therefore a helium turbine must be small, but the standard for large turbine design can be applied to such small turbine. Using the alternator as a brake, the turbo-expander was easily controllable electrically. The prototype turbo-expander was made, and the liquefaction test with it and MHD power generation test were carried out. (Kako, I.)

Expanding Role of T Cells in Human Autoimmune Diseases of the Central Nervous System

Directory of Open Access Journals (Sweden)

Deepti Pilli

2017-06-01

Full Text Available It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS autoimmune disorders that are currently postulated to be primarily T cell driven. We also explore the autoreactive T cell response in a recently emerging group of syndromes characterized by autoantibodies against neuronal cell-surface proteins. Common methodology implemented in T cell biology is further considered as it is an important determinant in their detection and characterization. An improved understanding of the contribution of autoreactive T cells expands our knowledge of the autoimmune response in CNS disorders and can offer novel methods of therapeutic intervention.

Use of inverse spatial conservation prioritization to avoid biological diversity loss outside protected areas.

Science.gov (United States)

Kareksela, Santtu; Moilanen, Atte; Tuominen, Seppo; Kotiaho, Janne S

2013-12-01

Globally expanding human land use sets constantly increasing pressure for maintenance of biological diversity and functioning ecosystems. To fight the decline of biological diversity, conservation science has broken ground with methods such as the operational model of systematic conservation planning (SCP), which focuses on design and on-the-ground implementation of conservation areas. The most commonly used method in SCP is reserve selection that focuses on the spatial design of reserve networks and their expansion. We expanded these methods by introducing another form of spatial allocation of conservation effort relevant for land-use zoning at the landscape scale that avoids negative ecological effects of human land use outside protected areas. We call our method inverse spatial conservation prioritization. It can be used to identify areas suitable for economic development while simultaneously limiting total ecological and environmental effects of that development at the landscape level by identifying areas with highest economic but lowest ecological value. Our method is not based on a priori targets, and as such it is applicable to cases where the effects of land use on, for example, individual species or ecosystem types are relatively small and would not lead to violation of regional or national conservation targets. We applied our method to land-use allocation to peat mining. Our method identified a combination of profitable production areas that provides the needed area for peat production while retaining most of the landscape-level ecological value of the ecosystem. The results of this inverse spatial conservation prioritization are being used in land-use zoning in the province of Central Finland. © 2013 Society for Conservation Biology.

Beyond the numbers: expanding the boundaries of neuropsychology.

Science.gov (United States)

Perry, William

2009-02-01

Beyond the Numbers: Expanding the Boundaries of Neuropsychology was Dr Perry's 2007 presidential address in the annual conference of the National Academy of Neuropsychology. In his address he discussed the achievements of the science of neuropsychology and highlighted some areas that exemplified the expansion of the boundaries of neuropsychology. These areas are: (i) the study of neuropsychological functioning in new or non-traditional populations, particularly seemingly healthy people and people with non-brain diseases; (ii) the interface of cognition and genetics; (iii) the use of the process approach as a means of understanding brain functioning; and (iv) a translational application to the science of neuropsychology.

Beyond the Numbers: Expanding the Boundaries of Neuropsychology†

Science.gov (United States)

Perry, William

2009-01-01

Beyond the Numbers: Expanding the Boundaries of Neuropsychology was Dr Perry's 2007 presidential address in the annual conference of the National Academy of Neuropsychology. In his address he discussed the achievements of the science of neuropsychology and highlighted some areas that exemplified the expansion of the boundaries of neuropsychology. These areas are: (i) the study of neuropsychological functioning in new or non-traditional populations, particularly seemingly healthy people and people with non-brain diseases; (ii) the interface of cognition and genetics; (iii) the use of the process approach as a means of understanding brain functioning; and (iv) a translational application to the science of neuropsychology. PMID:19395354

Characterization of pore-expanded amino-functionalized mesoporous silicas directly synthesized with dimethyldecylamine and its application for decolorization of sulphonated azo dyes

International Nuclear Information System (INIS)

Yang Hong; Feng Qiyan

2010-01-01

With dimethyldecylamine (DMDA) as the expander, a new kind of pore-expanded amino-functionalized mesoporous silicas (PEAFMS) was directly synthesized under mild alkali condition. The characteristics of PEAFMS sample demonstrated that the presence of DMDA markedly augmented the average pore diameter (19.04 nm) and strongly enhanced its decolorization ability. Subsequently, acid mordant dark yellow GG (YGG) and reactive red violet X-2R (RVX) were chosen to assess its adsorption capacity for sulphonated azo dyes. The effect of initial pH was investigated and the decolorization mechanism was illuminated. Three isotherms were conducted and the goodness of fit increased as the following order: Freundlich < Langmuir < Redlich-Peterson. The maximum adsorption capacities of YGG and RVX onto PEAFMS were 1.967 and 0.957 mmol/g, respectively. Adsorption kinetic processes were better predicted by the pseudo-second-order rate equation than the pseudo-first-order one. Adsorption thermodynamic results suggested that the adsorption behavior of both dyes onto PEAFMS was spontaneous with the chemical nature. In addition, the regeneration of PEAFMS was proved to be feasible using NaOH as the strippant. After five cycles, PEAFMS still possessed a favorable adsorption capacity for dyes. It is safely concluded that PEAFMS could be a potential adsorbent for the dye removal from wastewater.

Silicon microfabricated beam expander

International Nuclear Information System (INIS)

Othman, A.; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A.; Ain, M. F.

2015-01-01

The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed

Silicon microfabricated beam expander

Energy Technology Data Exchange (ETDEWEB)

Othman, A., E-mail: aliman@ppinang.uitm.edu.my; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A. [Faculty of Electrical Engineering, Universiti Teknologi MARA Malaysia, 40450, Shah Alam, Selangor (Malaysia); Ain, M. F. [School of Electrical and Electronic Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300,Nibong Tebal, Pulau Pinang (Malaysia)

2015-03-30

The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

CRISPR Editing in Biological and Biomedical Investigation.

Science.gov (United States)

Ju, Xing-Da; Xu, Jing; Sun, Zhong Sheng

2018-01-01

The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine. In biological research area, CRISPR has been widely adopted in both fundamental and applied research fields, such as genomic and epigenomic modification, genome-wide screening, cell and animal research, agriculture transforming, livestock breeding, food manufacture, industrial biotechnology, and gene drives in disease agents control. In biomedical research area, CRISPR has also shown its extensive applicability in the establishment of animal models for genetic disorders, generation of tissue donors, implementation of antimicrobial and antiviral studies, identification and assessment of new drugs, and even treatment for clinical diseases. However, there are still several problems to consider, and the biggest concerns are the off-target effects and ethical issues of this technology. In this prospect article, after highlighting recent development of CRISPR systems, we outline different applications and current limitations of CRISPR in biological and biomedical investigation. Finally, we provide a perspective on future development and potential risks of this multifunctional technology. J. Cell. Biochem. 119: 52-61, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Functional soil microbial diversity across Europe estimated by EEA, MicroResp and BIOLOG

DEFF Research Database (Denmark)

Winding, Anne; Rutgers, Michiel; Creamer, Rachel

consisting of 81 soil samples covering five Biogeograhical Zones and three land-uses in order to test the sensitivity, ease and cost of performance and biological significance of the data output. The techniques vary in how close they are to in situ functions; dependency on growth during incubation......Soil microorganisms are abundant and essential for the bio-geochemical processes of soil, soil quality and soil ecosystem services. All this is dependent on the actual functions the microbial communities are performing in the soil. Measuring soil respiration has for many years been the basis...... of estimating soil microbial activity. However, today several techniques are in use for determining microbial functional diversity and assessing soil biodiversity: Methods based on CO2 development by the microbes such as substrate induced respiration (SIR) on specific substrates have lead to the development...

Treatment of Benign Tracheal Stenosis Utilizing Self-Expanding Nitinol Stents

International Nuclear Information System (INIS)

Sesterhenn, Andreas M.; Wagner, Hans-Joachim; Alfke, Heiko; Werner, Jochen A.; Lippert, Burkard M.

2004-01-01

We assessed the results of self-expanding metallic stent insertion into benign proximal tracheal stenosis in patients not appropriate or unfit for surgical repair. Proximal benign tracheal stenoses had occurred in 11 patients (7 men, 4 women, mean age 68.8 years) after long-time intubation (n = 6), tracheostomy (n = 4), or chondropathia (n = 1). Fourteen self-expanding nitinol stents were placed in the patients under general anesthesia with endoscopical and fluoroscopical guidance. Stent insertion was successful in all cases and led to immediate relief of the morphological and functional airway obstruction. No immediate complications were noted. During the mean follow-up period of 67.5 weeks we observed one recurrent dyspnea 3 months after implantation and granuloma formation at the stent insertion site in another patient. Both complications were successfully treated with additional stent insertion in one case and laser resection of granulomas in the other. Self-expanding nitinol stents should be considered for the treatment of benign proximal tracheal obstruction in selected patients for whom surgical repair is contraindicated

Gross Motor Function Classification System Expanded & Revised (GMFCS E & R: reliability between therapists and parents in Brazil

Directory of Open Access Journals (Sweden)

Daniela B. R. Silva

2013-10-01

Full Text Available BACKGROUND: Several studies have demonstrated the importance of using the Gross Motor Function Classification System (GMFCS to classify gross motor function in children with cerebral palsy, but the reliability of the expanded and revised version has not been examined in Brazil (GMFCS E & R. OBJECTIVE:: To determine the intra- and inter-rater reliability of the Portuguese-Brazil version of the GMFCS E & R applied by therapists and compare to classification provided by parents of children with cerebral palsy. METHOD: Data were obtained from 90 children with cerebral palsy, aged 4 to 18 years old, attending the neurology or rehabilitation service of a Brazilian hospital. Therapists classified the children's motor function using the GMFCS E & R and parents used the Brazilian Portuguese version of the GMFCS Family Report Questionnaire. Intra- and inter-rater reliability was obtained through percentage agreement and Cohen's unweighted Kappa statistics (k. The Chi-square test was used to identify significant differences in the classification of parents and therapists. RESULTS: Almost perfect agreement was reached between the therapists [K=0.90 (95% confidence interval 0.83-0.97] and intra-raters (therapists with K=1.00 [95% confidence interval (1.00-1.00], p<0.001. Agreement between therapists and parents was substantial (k=0.716, confidence interval 0.596-0.836, though parents classify gross motor impairment more severely than therapists (p=0.04. CONCLUSIONS: The Portuguese version of the GMFCS E & R is reliable for use by parents and therapists. Parents tend to classify their children's limitations more severely, because they know their performance in different environments.

Expanding perspectives on cognition in humans, animals, and machines.

Science.gov (United States)

Gomez-Marin, Alex; Mainen, Zachary F

2016-04-01

Over the past decade neuroscience has been attacking the problem of cognition with increasing vigor. Yet, what exactly is cognition, beyond a general signifier of anything seemingly complex the brain does? Here, we briefly review attempts to define, describe, explain, build, enhance and experience cognition. We highlight perspectives including psychology, molecular biology, computation, dynamical systems, machine learning, behavior and phenomenology. This survey of the landscape reveals not a clear target for explanation but a pluralistic and evolving scene with diverse opportunities for grounding future research. We argue that rather than getting to the bottom of it, over the next century, by deconstructing and redefining cognition, neuroscience will and should expand rather than merely reduce our concept of the mind. Copyright © 2016 Elsevier Ltd. All rights reserved.

The emerging molecular biology toolbox for the study of long noncoding RNA biology.

Science.gov (United States)

Fok, Ezio T; Scholefield, Janine; Fanucchi, Stephanie; Mhlanga, Musa M

2017-10-01

Long noncoding RNAs (lncRNAs) have been implicated in many biological processes. However, due to the unique nature of lncRNAs and the consequential difficulties associated with their characterization, there is a growing disparity between the rate at which lncRNAs are being discovered and the assignment of biological function to these transcripts. Here we present a molecular biology toolbox equipped to help dissect aspects of lncRNA biology and reveal functionality. We outline an approach that begins with a broad survey of genome-wide, high-throughput datasets to identify potential lncRNA candidates and then narrow the focus on specific methods that are well suited to interrogate the transcripts of interest more closely. This involves the use of imaging-based strategies to validate these candidates and observe the behaviors of these transcripts at single molecule resolution in individual cells. We also describe the use of gene editing tools and interactome capture techniques to interrogate functionality and infer mechanism, respectively. With the emergence of lncRNAs as important molecules in healthy and diseased cellular function, it remains crucial to deepen our understanding of their biology.

Reduction of shock induced noise in imperfectly expanded supersonic jets using convex optimization

Science.gov (United States)

Adhikari, Sam

2007-11-01

Imperfectly expanded jets generate screech noise. The imbalance between the backpressure and the exit pressure of the imperfectly expanded jets produce shock cells and expansion or compression waves from the nozzle. The instability waves and the shock cells interact to generate the screech sound. The mathematical model consists of cylindrical coordinate based full Navier-Stokes equations and large-eddy-simulation turbulence modeling. Analytical and computational analysis of the three-dimensional helical effects provide a model that relates several parameters with shock cell patterns, screech frequency and distribution of shock generation locations. Convex optimization techniques minimize the shock cell patterns and the instability waves. The objective functions are (convex) quadratic and the constraint functions are affine. In the quadratic optimization programs, minimization of the quadratic functions over a set of polyhedrons provides the optimal result. Various industry standard methods like regression analysis, distance between polyhedra, bounding variance, Markowitz optimization, and second order cone programming is used for Quadratic Optimization.

A Tricky Trait: Applying the Fruits of the "Function Debate" in the Philosophy of Biology to the "Venom Debate" in the Science of Toxinology.

Science.gov (United States)

Jackson, Timothy N W; Fry, Bryan G

2016-09-07

The "function debate" in the philosophy of biology and the "venom debate" in the science of toxinology are conceptually related. Venom systems are complex multifunctional traits that have evolved independently numerous times throughout the animal kingdom. No single concept of function, amongst those popularly defended, appears adequate to describe these systems in all their evolutionary contexts and extant variations. As such, a pluralistic view of function, previously defended by some philosophers of biology, is most appropriate. Venom systems, like many other functional traits, exist in nature as points on a continuum and the boundaries between "venomous" and "non-venomous" species may not always be clearly defined. This paper includes a brief overview of the concept of function, followed by in-depth discussion of its application to venom systems. A sound understanding of function may aid in moving the venom debate forward. Similarly, consideration of a complex functional trait such as venom may be of interest to philosophers of biology.

Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects

Science.gov (United States)

Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects Schreinemachers DM, Ghio AJ, Cascio WE, Sobus JR. U.S. EPA, RTP, NC, USA Perchlorate (ClO4-), an environmental pollutant, is a known thyroid toxicant and...

Particle creation and particle number in an expanding universe

International Nuclear Information System (INIS)

Parker, Leonard

2012-01-01

I describe the logical basis of the method that I developed in 1962 and 1963 to define a quantum operator corresponding to the observable particle number of a quantized free scalar field in a spatially-flat isotropically expanding (and/or contracting) universe. This work also showed for the first time that particles were created from the vacuum by the curved spacetime of an expanding spatially-flat Friedmann–Lemaître–Robertson–Walker (FLRW) universe. The same process is responsible for creating the nearly scale-invariant spectrum of quantized perturbations of the inflaton scalar field during the inflationary stage of the expansion of the universe. I explain how the method that I used to obtain the observable particle number operator involved adiabatic invariance of the particle number (hence, the name adiabatic regularization) and the quantum theory of measurement of particle number in an expanding universe. I also show how I was led in a surprising way, to the discovery in 1964 that there would be no particle creation by these spatially-flat FLRW universes for free fields of any integer or half-integer spin satisfying field equations that are invariant under conformal transformations of the metric. The methods I used to define adiabatic regularization for particle number were based on generally-covariant concepts like adiabatic invariance and measurement that were fundamental and determined results that were unique to each given adiabatic order. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical in honour of Stuart Dowker's 75th birthday devoted to ‘Applications of zeta functions and other spectral functions in mathematics and physics’. (paper)

A growing family: the expanding universe of the bacterial cytoskeleton.

Science.gov (United States)

Ingerson-Mahar, Michael; Gitai, Zemer

2012-01-01

Cytoskeletal proteins are important mediators of cellular organization in both eukaryotes and bacteria. In the past, cytoskeletal studies have largely focused on three major cytoskeletal families, namely the eukaryotic actin, tubulin, and intermediate filament (IF) proteins and their bacterial homologs MreB, FtsZ, and crescentin. However, mounting evidence suggests that these proteins represent only the tip of the iceberg, as the cellular cytoskeletal network is far more complex. In bacteria, each of MreB, FtsZ, and crescentin represents only one member of large families of diverse homologs. There are also newly identified bacterial cytoskeletal proteins with no eukaryotic homologs, such as WACA proteins and bactofilins. Furthermore, there are universally conserved proteins, such as the metabolic enzyme CtpS, that assemble into filamentous structures that can be repurposed for structural cytoskeletal functions. Recent studies have also identified an increasing number of eukaryotic cytoskeletal proteins that are unrelated to actin, tubulin, and IFs, such that expanding our understanding of cytoskeletal proteins is advancing the understanding of the cell biology of all organisms. Here, we summarize the recent explosion in the identification of new members of the bacterial cytoskeleton and describe a hypothesis for the evolution of the cytoskeleton from self-assembling enzymes. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Expanded Mixed Multiscale Finite Element Methods and Their Applications for Flows in Porous Media

KAUST Repository

Jiang, L.

2012-01-01

We develop a family of expanded mixed multiscale finite element methods (MsFEMs) and their hybridizations for second-order elliptic equations. This formulation expands the standard mixed multiscale finite element formulation in the sense that four unknowns (hybrid formulation) are solved simultaneously: pressure, gradient of pressure, velocity, and Lagrange multipliers. We use multiscale basis functions for both the velocity and the gradient of pressure. In the expanded mixed MsFEM framework, we consider both separable and nonseparable spatial scales. Specifically, we analyze the methods in three categories: periodic separable scales, G-convergent separable scales, and a continuum of scales. When there is no scale separation, using some global information can significantly improve the accuracy of the expanded mixed MsFEMs. We present a rigorous convergence analysis of these methods that includes both conforming and nonconforming formulations. Numerical results are presented for various multiscale models of flow in porous media with shale barriers that illustrate the efficacy of the proposed family of expanded mixed MsFEMs. © 2012 Society for Industrial and Applied Mathematics.

Biology of bone and how it orchestrates the form and function of the skeleton

Science.gov (United States)

Sommerfeldt, D. W.; Rubin, C. T.

2001-01-01

The principal role of the skeleton is to provide structural support for the body. While the skeleton also serves as the body's mineral reservoir, the mineralized structure is the very basis of posture, opposes muscular contraction resulting in motion, withstands functional load bearing, and protects internal organs. Although the mass and morphology of the skeleton is defined, to some extent, by genetic determinants, it is the tissue's ability to remodel--the local resorption and formation of bone--which is responsible for achieving this intricate balance between competing responsibilities. The aim of this review is to address bone's form-function relationship, beginning with extensive research in the musculoskeletal disciplines, and focusing on several recent cellular and molecular discoveries which help understand the complex interdependence of bone cells, growth factors, physical stimuli, metabolic demands, and structural responsibilities. With a clinical and spine-oriented audience in mind, the principles of bone cell and molecular biology and physiology are presented, and an attempt has been made to incorporate epidemiologic data and therapeutic implications. Bone research remains interdisciplinary by nature, and a deeper understanding of bone biology will ultimately lead to advances in the treatment of diseases and injuries to bone itself.

US Competitiveness in Synthetic Biology.

Science.gov (United States)

Gronvall, Gigi Kwik

2015-01-01

Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

Science.gov (United States)

Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

2016-02-01

The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

From transcriptome to biological function: environmental stress in an ectothermic vertebrate, the coral reef fish Pomacentrus moluccensis

Directory of Open Access Journals (Sweden)

Ward Alister C

2007-10-01

Full Text Available Abstract Background Our understanding of the importance of transcriptional regulation for biological function is continuously improving. We still know, however, comparatively little about how environmentally induced stress affects gene expression in vertebrates, and the consistency of transcriptional stress responses to different types of environmental stress. In this study, we used a multi-stressor approach to identify components of a common stress response as well as components unique to different types of environmental stress. We exposed individuals of the coral reef fish Pomacentrus moluccensis to hypoxic, hyposmotic, cold and heat shock and measured the responses of approximately 16,000 genes in liver. We also compared winter and summer responses to heat shock to examine the capacity for such responses to vary with acclimation to different ambient temperatures. Results We identified a series of gene functions that were involved in all stress responses examined here, suggesting some common effects of stress on biological function. These common responses were achieved by the regulation of largely independent sets of genes; the responses of individual genes varied greatly across different stress types. In response to heat exposure over five days, a total of 324 gene loci were differentially expressed. Many heat-responsive genes had functions associated with protein turnover, metabolism, and the response to oxidative stress. We were also able to identify groups of co-regulated genes, the genes within which shared similar functions. Conclusion This is the first environmental genomic study to measure gene regulation in response to different environmental stressors in a natural population of a warm-adapted ectothermic vertebrate. We have shown that different types of environmental stress induce expression changes in genes with similar gene functions, but that the responses of individual genes vary between stress types. The functions of heat

Expander Codes

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 1. Expander Codes - The Sipser–Spielman Construction. Priti Shankar. General Article Volume 10 ... Author Affiliations. Priti Shankar1. Department of Computer Science and Automation, Indian Institute of Science Bangalore 560 012, India.

Continuous-time random-walk model for anomalous diffusion in expanding media

Science.gov (United States)

Le Vot, F.; Abad, E.; Yuste, S. B.

2017-09-01

Expanding media are typical in many different fields, e.g., in biology and cosmology. In general, a medium expansion (contraction) brings about dramatic changes in the behavior of diffusive transport properties such as the set of positional moments and the Green's function. Here, we focus on the characterization of such effects when the diffusion process is described by the continuous-time random-walk (CTRW) model. As is well known, when the medium is static this model yields anomalous diffusion for a proper choice of the probability density function (pdf) for the jump length and the waiting time, but the behavior may change drastically if a medium expansion is superimposed on the intrinsic random motion of the diffusing particle. For the case where the jump length and the waiting time pdfs are long-tailed, we derive a general bifractional diffusion equation which reduces to a normal diffusion equation in the appropriate limit. We then study some particular cases of interest, including Lévy flights and subdiffusive CTRWs. In the former case, we find an analytical exact solution for the Green's function (propagator). When the expansion is sufficiently fast, the contribution of the diffusive transport becomes irrelevant at long times and the propagator tends to a stationary profile in the comoving reference frame. In contrast, for a contracting medium a competition between the spreading effect of diffusion and the concentrating effect of contraction arises. In the specific case of a subdiffusive CTRW in an exponentially contracting medium, the latter effect prevails for sufficiently long times, and all the particles are eventually localized at a single point in physical space. This "big crunch" effect, totally absent in the case of normal diffusion, stems from inefficient particle spreading due to subdiffusion. We also derive a hierarchy of differential equations for the moments of the transport process described by the subdiffusive CTRW model in an expanding medium

Continuous-time random-walk model for anomalous diffusion in expanding media.

Science.gov (United States)

Le Vot, F; Abad, E; Yuste, S B

2017-09-01

Expanding media are typical in many different fields, e.g., in biology and cosmology. In general, a medium expansion (contraction) brings about dramatic changes in the behavior of diffusive transport properties such as the set of positional moments and the Green's function. Here, we focus on the characterization of such effects when the diffusion process is described by the continuous-time random-walk (CTRW) model. As is well known, when the medium is static this model yields anomalous diffusion for a proper choice of the probability density function (pdf) for the jump length and the waiting time, but the behavior may change drastically if a medium expansion is superimposed on the intrinsic random motion of the diffusing particle. For the case where the jump length and the waiting time pdfs are long-tailed, we derive a general bifractional diffusion equation which reduces to a normal diffusion equation in the appropriate limit. We then study some particular cases of interest, including Lévy flights and subdiffusive CTRWs. In the former case, we find an analytical exact solution for the Green's function (propagator). When the expansion is sufficiently fast, the contribution of the diffusive transport becomes irrelevant at long times and the propagator tends to a stationary profile in the comoving reference frame. In contrast, for a contracting medium a competition between the spreading effect of diffusion and the concentrating effect of contraction arises. In the specific case of a subdiffusive CTRW in an exponentially contracting medium, the latter effect prevails for sufficiently long times, and all the particles are eventually localized at a single point in physical space. This "big crunch" effect, totally absent in the case of normal diffusion, stems from inefficient particle spreading due to subdiffusion. We also derive a hierarchy of differential equations for the moments of the transport process described by the subdiffusive CTRW model in an expanding medium

Functional profiles reveal unique ecological roles of various biological soil crust organisms

Science.gov (United States)

Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

2011-01-01

1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

Function-Based Algorithms for Biological Sequences

Science.gov (United States)

Mohanty, Pragyan Sheela P.

2015-01-01

Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

After the Greeting: Realizing the Potential of Physical Models in Cell Biology.

Science.gov (United States)

Paluch, Ewa K

2015-12-01

Biophysics is increasingly taking center stage in cell biology as the tools for precise quantifications of cellular behaviors expand. Interdisciplinary approaches, combining quantitative physical modeling with cell biology, are of growing interest to journal editors, funding agencies, and hiring committees. However, despite an ever-increasing emphasis on the importance of interdisciplinary research, the student trained in biology may still be at a loss as to what it actually means. I discuss here some considerations on how to achieve meaningful and high-quality interdisciplinary work. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of a bent Laue beam-expanding double-crystal monochromator for biomedical X-ray imaging

International Nuclear Information System (INIS)

Martinson, Mercedes; Samadi, Nazanin; Belev, George; Bassey, Bassey; Lewis, Rob; Aulakh, Gurpreet; Chapman, Dean

2014-01-01

A bent Laue beam-expanding double-crystal monochromator was developed and tested at the Biomedical Imaging and Therapy beamline at the Canadian Light Source. The expander will reduce scanning time for micro-computed tomography and allow dynamic imaging that has not previously been possible at this beamline. The Biomedical Imaging and Therapy (BMIT) beamline at the Canadian Light Source has produced some excellent biological imaging data. However, the disadvantage of a small vertical beam limits its usability in some applications. Micro-computed tomography (micro-CT) imaging requires multiple scans to produce a full projection, and certain dynamic imaging experiments are not possible. A larger vertical beam is desirable. It was cost-prohibitive to build a longer beamline that would have produced a large vertical beam. Instead, it was proposed to develop a beam expander that would create a beam appearing to originate at a source much farther away. This was accomplished using a bent Laue double-crystal monochromator in a non-dispersive divergent geometry. The design and implementation of this beam expander is presented along with results from the micro-CT and dynamic imaging tests conducted with this beam. Flux (photons per unit area per unit time) has been measured and found to be comparable with the existing flat Bragg double-crystal monochromator in use at BMIT. This increase in overall photon count is due to the enhanced bandwidth of the bent Laue configuration. Whilst the expanded beam quality is suitable for dynamic imaging and micro-CT, further work is required to improve its phase and coherence properties

Determining the impacts of trawling on benthic function in European waters : a biological traits approach

DEFF Research Database (Denmark)

Bolam, Stefan; Kenny, Andrew; Garcia, Clement

characteristics, have allowed us to better understand the interactions between the benthic fauna and their environment at a functional level. We present the initial findings of work conducted under the auspices of the EU-funded project ‘BENTHIS’ which aims to improve our understanding of the impacts of trawling...... on benthic ecosystem functioning over much larger spatial scales than previously undertaken. Biological traits information from 887 stations across European waters (Norwegian, UK, Belgian, Dutch, Danish waters, the Mediterranean and Black Sea) were analysed to: i) quantify the relationships between infaunal...

The role of ontologies in biological and biomedical research: a functional perspective

KAUST Repository

Hoehndorf, Robert

2015-04-10

Ontologies are widely used in biological and biomedical research. Their success lies in their combination of four main features present in almost all ontologies: provision of standard identifiers for classes and relations that represent the phenomena within a domain; provision of a vocabulary for a domain; provision of metadata that describes the intended meaning of the classes and relations in ontologies; and the provision of machine-readable axioms and definitions that enable computational access to some aspects of the meaning of classes and relations. While each of these features enables applications that facilitate data integration, data access and analysis, a great potential lies in the possibility of combining these four features to support integrative analysis and interpretation of multimodal data. Here, we provide a functional perspective on ontologies in biology and biomedicine, focusing on what ontologies can do and describing how they can be used in support of integrative research. We also outline perspectives for using ontologies in data-driven science, in particular their application in structured data mining and machine learning applications.

The role of ontologies in biological and biomedical research: a functional perspective

KAUST Repository

Hoehndorf, Robert; Schofield, P. N.; Gkoutos, G. V.

2015-01-01

Ontologies are widely used in biological and biomedical research. Their success lies in their combination of four main features present in almost all ontologies: provision of standard identifiers for classes and relations that represent the phenomena within a domain; provision of a vocabulary for a domain; provision of metadata that describes the intended meaning of the classes and relations in ontologies; and the provision of machine-readable axioms and definitions that enable computational access to some aspects of the meaning of classes and relations. While each of these features enables applications that facilitate data integration, data access and analysis, a great potential lies in the possibility of combining these four features to support integrative analysis and interpretation of multimodal data. Here, we provide a functional perspective on ontologies in biology and biomedicine, focusing on what ontologies can do and describing how they can be used in support of integrative research. We also outline perspectives for using ontologies in data-driven science, in particular their application in structured data mining and machine learning applications.

Withdrawal: Expanding a Key Addiction Construct.

Science.gov (United States)

Piper, Megan E

2015-12-01

Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The expanding universe: an introduction

OpenAIRE

Pössel, Markus

2017-01-01

An introduction to the physics and mathematics of the expanding universe, using no more than high-school level / undergraduate mathematics. Covered are the basics of scale factor expansion, the dynamics of the expanding universe, various distance concepts and the generalized redshift-luminosity relation, among other topics.

Bio-templated CdSe quantum dots green synthesis in the functional protein, lysozyme, and biological activity investigation

International Nuclear Information System (INIS)

Wang, Qisui; Li, Song; Liu, Peng; Min, Xinmin

2012-01-01

Bifunctional fluorescence (CdSe Quantum Dots) – protein (Lysozyme) nanocomposites were synthesized at room temperature by a protein-directed, solution-phase, green-synthetic method. Fluorescence (FL) and absorption spectra showed that CdSe QDs were prepared successfully with Lyz. The average particle size and crystalline structure of QDs were investigated by high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD), respectively. With attenuated total reflection-fourier transform infrared (ATR-FTIR) spectra and thermogravimetric (TG) analysis, it was confirmed that there is interaction between QDs and amide I, amide II groups in Lyz. FL polarization was measured and FL imaging was done to monitor whether QDs could be responsible for possible changes in the conformation and activity of Lyz. Interestingly, the results showed Lyz still retain the biological activity after formation of QDs, but the secondary structure of the Lyz was changed. And the advantage of this synthesis method is producing excellent fluorescent QDs with specifically biological function. -- Highlights: ► Lysozyme-directed green synthesis of CdSe quantum dots. ► Lysozyme still retain the biological activity after formation of CdSe. ► The method is the production of fluorescent QDs with highly specific and functions.

Embryonic stem cell interactomics: the beginning of a long road to biological function.

Science.gov (United States)

Yousefi, Maram; Hajihoseini, Vahid; Jung, Woojin; Hosseinpour, Batol; Rassouli, Hassan; Lee, Bonghee; Baharvand, Hossein; Lee, KiYoung; Salekdeh, Ghasem Hosseini

2012-12-01

Embryonic stem cells (ESCs) are capable of unlimited self-renewal while maintaining pluripotency. They are of great interest in regenerative medicine due to their ability to differentiate into all cell types of the three embryonic germ layers. Recently, induced pluripotent stem cells (iPSCs) have shown similarities to ESCs and thus promise great therapeutic potential in regenerative medicine. Despite progress in stem cell biology, our understanding of the exact mechanisms by which pluripotency and self-renewal are established and maintained is largely unknown. A better understanding of these processes may lead to discovery of alternative ways for reprogramming, differentiation and more reliable applications of stem cells in therapies. It has become evident that proteins generally function as members of large complexes that are part of a more complex network. Therefore, the identification of protein-protein interactions (PPI) is an efficient strategy for understanding protein function and regulation. Systematic genome-wide and pathway-specific PPI analysis of ESCs has generated a network of ESC proteins, including major transcription factors. These PPI networks of ESCs may contribute to a mechanistic understanding of self-renewal and pluripotency. In this review we describe different experimental approaches for the identification of PPIs along with various databases. We discuss biological findings and technical challenges encountered with interactome studies of pluripotent stem cells, and provide insight into how interactomics is likely to develop.

Biological mechanisms, one molecule at a time

Science.gov (United States)

Tinoco, Ignacio; Gonzalez, Ruben L.

2011-01-01

The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

Minimal information: an urgent need to assess the functional reliability of recombinant proteins used in biological experiments

Directory of Open Access Journals (Sweden)

de Marco Ario

2008-07-01

Full Text Available Abstract Structural characterization of proteins used in biological experiments is largely neglected. In most publications, the information available is totally insufficient to judge the functionality of the proteins used and, therefore, the significance of identified protein-protein interactions (was the interaction specific or due to unspecific binding of misfolded protein regions? or reliability of kinetic and thermodynamic data (how much protein was in its native form?. As a consequence, the results of single experiments might not only become questionable, but the whole reliability of systems biology, built on these fundaments, would be weakened. The introduction of Minimal Information concerning purified proteins to add as metadata to the main body of a manuscript would render straightforward the assessment of their functional and structural qualities and, consequently, of results obtained using these proteins. Furthermore, accepted standards for protein annotation would simplify data comparison and exchange. This article has been envisaged as a proposal for aggregating scientists who share the opinion that the scientific community needs a platform for Minimum Information for Protein Functionality Evaluation (MIPFE.

A Rapidly Expanding Bose-Einstein Condensate: An Expanding Universe in the Lab

Science.gov (United States)

Eckel, S.; Kumar, A.; Jacobson, T.; Spielman, I. B.; Campbell, G. K.

2018-04-01

We study the dynamics of a supersonically expanding, ring-shaped Bose-Einstein condensate both experimentally and theoretically. The expansion redshifts long-wavelength excitations, as in an expanding universe. After expansion, energy in the radial mode leads to the production of bulk topological excitations—solitons and vortices—driving the production of a large number of azimuthal phonons and, at late times, causing stochastic persistent currents. These complex nonlinear dynamics, fueled by the energy stored coherently in one mode, are reminiscent of a type of "preheating" that may have taken place at the end of inflation.

Making United States Integrated Ocean Observing System (U.S. IOOS) inclusive of marine biological resources

Science.gov (United States)

Moustahfid, H.; Potemra, J.; Goldstein, P.; Mendelssohn, R.; Desrochers, A.

2011-01-01

An important Data Management and Communication (DMAC) goal is to enable a multi-disciplinary view of the ocean environment by facilitating discovery and integration of data from various sources, projects and scientific domains. United States Integrated Ocean Observing System (U.S. IOOS) DMAC functional requirements are based upon guidelines for standardized data access services, data formats, metadata, controlled vocabularies, and other conventions. So far, the data integration effort has focused on geophysical U.S. IOOS core variables such as temperature, salinity, ocean currents, etc. The IOOS Biological Observations Project is addressing the DMAC requirements that pertain to biological observations standards and interoperability applicable to U.S. IOOS and to various observing systems. Biological observations are highly heterogeneous and the variety of formats, logical structures, and sampling methods create significant challenges. Here we describe an informatics framework for biological observing data (e.g. species presence/absence and abundance data) that will expand information content and reconcile standards for the representation and integration of these biological observations for users to maximize the value of these observing data. We further propose that the approach described can be applied to other datasets generated in scientific observing surveys and will provide a vehicle for wider dissemination of biological observing data. We propose to employ data definition conventions that are well understood in U.S. IOOS and to combine these with ratified terminologies, policies and guidelines. ?? 2011 MTS.

Synthetic Biology: Putting Synthesis into Biology

Science.gov (United States)

Liang, Jing; Luo, Yunzi; Zhao, Huimin

2010-01-01

The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

Molecular Sociology: Further Insights from Biological and Environmental Aspects

Directory of Open Access Journals (Sweden)

Ahed Jumah Mahmoud Al-Khatib

2015-11-01

Full Text Available The present study expanded our previous study in which features of molecular sociology were mentioned. In this study, we added the microbial dimensions in which it is thought that religiosity may be impacted by microbes that manipulate brains to create better conditions for their existence. This hypothesis is called “biomeme hypothesis”. We talked about other environmental impacts on human behaviors through three studies in which exposure to lead caused violent behaviors ending with arresting in prisons. By conclusion, the present study has expanded our horizon about interferences on various levels including biological and environmental impacts with our behaviors. Although we are convinced that behavior is a very diverse and complex phenomenon and cannot be understood within certain frame as either biologically or environmentally, but further new insights are possible to participate in better understanding of human behaviors. Many behaviors have their roots in religion, and we showed how religious rituals may be affected by some microbes that make to form a microenvironment within the host for microbial benefits.

Where Synthetic Biology Meets ET

Science.gov (United States)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

Directory of Open Access Journals (Sweden)

For Yue Tso

Full Text Available A better understanding of how the biological functions of the HIV-1 envelope (Env changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

The development of peptide-based interfacial biomaterials for generating biological functionality on the surface of bioinert materials.

Science.gov (United States)

Meyers, Steven R; Khoo, Xiaojuan; Huang, Xin; Walsh, Elisabeth B; Grinstaff, Mark W; Kenan, Daniel J

2009-01-01

Biomaterials used in implants have traditionally been selected based on their mechanical properties, chemical stability, and biocompatibility. However, the durability and clinical efficacy of implantable biomedical devices remain limited in part due to the absence of appropriate biological interactions at the implant interface and the lack of integration into adjacent tissues. Herein, we describe a robust peptide-based coating technology capable of modifying the surface of existing biomaterials and medical devices through the non-covalent binding of modular biofunctional peptides. These peptides contain at least one material binding sequence and at least one biologically active sequence and thus are termed, "Interfacial Biomaterials" (IFBMs). IFBMs can simultaneously bind the biomaterial surface while endowing it with desired biological functionalities at the interface between the material and biological realms. We demonstrate the capabilities of model IFBMs to convert native polystyrene, a bioinert surface, into a bioactive surface that can support a range of cell activities. We further distinguish between simple cell attachment with insufficient integrin interactions, which in some cases can adversely impact downstream biology, versus biologically appropriate adhesion, cell spreading, and cell survival mediated by IFBMs. Moreover, we show that we can use the coating technology to create spatially resolved patterns of fluorophores and cells on substrates and that these patterns retain their borders in culture.

On the limitations of standard statistical modeling in biological systems: a full Bayesian approach for biology.

Science.gov (United States)

Gomez-Ramirez, Jaime; Sanz, Ricardo

2013-09-01

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist. Copyright © 2013 Elsevier Ltd. All rights reserved.

Myostatin: expanding horizons.

Science.gov (United States)

Sharma, Mridula; McFarlane, Craig; Kambadur, Ravi; Kukreti, Himani; Bonala, Sabeera; Srinivasan, Shruti

2015-08-01

Myostatin is a secreted growth and differentiation factor that belongs to the TGF-β superfamily. Myostatin is predominantly synthesized and expressed in skeletal muscle and thus exerts a huge impact on muscle growth and function. In keeping with its negative role in myogenesis, myostatin expression is tightly regulated at several levels including epigenetic, transcriptional, post-transcriptional, and post-translational. New revelations regarding myostatin regulation also offer mechanisms that could be exploited for developing myostatin antagonists. Increasingly, it is becoming clearer that besides its conventional role in muscle, myostatin plays a critical role in metabolism. Hence, molecular mechanisms by which myostatin regulates several key metabolic processes need to be further explored. © 2015 International Union of Biochemistry and Molecular Biology.

Synthetic biological networks

International Nuclear Information System (INIS)

Archer, Eric; Süel, Gürol M

2013-01-01

Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

The Stellar Populations Inside Expanding HI Shells in the Spiral Galaxy M33

Science.gov (United States)

Walterbos, Rene

1997-07-01

Because of its vigorous star formation activity, favorable inclination, and relative proximity, M33 is an ideal laboratory for the study of expanding HI shells in spiral galaxies. Theoretical models show that the energy deposited into the ISM by high mass stars in OB associations is capable of creating HI superbubbles. However, sparse observational evidence exists to test these models in detail. One essential ingredient of such a test is an improved census of stellar populations inside expanding HI shells. Using multi-color archival HST images of M33, we will {1} verify that association ages are consistent with dynamical ages of related shells and with ages from model predictions for bubbles of matching size and kinematics; {2} Constrain the IMF for each association by combining integrated ground-based HAlpha fluxes with the population age, present day mass function, and luminosity function derived from WFPC2 data; {3} Use this information to infer which fraction of the integrated stellar mechanical luminosity is transferred to a shell over its lifetime. Ground-based observations of associations inside expanding shells lack the UV-sensitivity and spatial resolution to adequately address these issues. Our sample of expanding neutral shells in M33 was selected using a new automated method for analysis of HI datacubes. From this robust catalog we have identified more than 30 HI supershells in M33 already imaged with WFPC2 in suitable broadband filters {F160BW, F170W, F336W, F439W, F555W, and F814W}.

Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.

Science.gov (United States)

Howard, Rebecca J; Carnevale, Vincenzo; Delemotte, Lucie; Hellmich, Ute A; Rothberg, Brad S

2018-04-01

Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process-for example with neuroactive drugs-demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data management and conceptual alignment. Here, we seek to provide contemporary context, concrete examples, and a look to the future for bridging disciplinary gaps in biological ion transport. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain. Copyright © 2017 Elsevier B.V. All rights reserved.

An expanded framework for the advanced computational testing and simulation toolkit

Energy Technology Data Exchange (ETDEWEB)

Marques, Osni A.; Drummond, Leroy A.

2003-11-09

The Advanced Computational Testing and Simulation (ACTS) Toolkit is a set of computational tools developed primarily at DOE laboratories and is aimed at simplifying the solution of common and important computational problems. The use of the tools reduces the development time for new codes and the tools provide functionality that might not otherwise be available. This document outlines an agenda for expanding the scope of the ACTS Project based on lessons learned from current activities. Highlights of this agenda include peer-reviewed certification of new tools; finding tools to solve problems that are not currently addressed by the Toolkit; working in collaboration with other software initiatives and DOE computer facilities; expanding outreach efforts; promoting interoperability, further development of the tools; and improving functionality of the ACTS Information Center, among other tasks. The ultimate goal is to make the ACTS tools more widely used and more effective in solving DOE's and the nation's scientific problems through the creation of a reliable software infrastructure for scientific computing.

A Rapidly Expanding Bose-Einstein Condensate: An Expanding Universe in the Lab

Directory of Open Access Journals (Sweden)

S. Eckel

2018-04-01

Full Text Available We study the dynamics of a supersonically expanding, ring-shaped Bose-Einstein condensate both experimentally and theoretically. The expansion redshifts long-wavelength excitations, as in an expanding universe. After expansion, energy in the radial mode leads to the production of bulk topological excitations—solitons and vortices—driving the production of a large number of azimuthal phonons and, at late times, causing stochastic persistent currents. These complex nonlinear dynamics, fueled by the energy stored coherently in one mode, are reminiscent of a type of “preheating” that may have taken place at the end of inflation.

Surface functionalization of bioactive glasses with natural molecules of biological significance, Part I: Gallic acid as model molecule

Science.gov (United States)

Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

2013-12-01

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) and its derivatives are a group of biomolecules (polyphenols) obtained from plants. They have effects which are potentially beneficial to heath, for example they are antioxidant, anticarcinogenic and antibacterial, as recently investigated in many fields such as medicine, food and plant sciences. The main drawbacks of these molecules are both low stability and bioavailability. In this research work the opportunity to graft GA to bioactive glasses is investigated, in order to deliver the undamaged biological molecule into the body, using the biomaterial surfaces as a localized carrier. GA was considered for functionalization since it is a good model molecule for polyphenols and presents several interesting biological activities, like antibacterial, antioxidant and anticarcinogenic properties. Two different silica based bioactive glasses (SCNA and CEL2), with different reactivity, were employed as substrates. UV photometry combined with the Folin&Ciocalteu reagent was adopted to test the concentration of GA in uptake solution after functionalization. This test verified how much GA consumption occurred with surface modification and it was also used on solid samples to test the presence of GA on functionalized glasses. XPS and SEM-EDS techniques were employed to characterize the modification of material surface properties and functional group composition before and after functionalization.

On Beyond Star Trek, the Role of Synthetic Biology in Nasa's Missions

Science.gov (United States)

Rothschild, Lynn J.

2016-01-01

The time has come to for NASA to exploit the nascent field of synthetic biology in pursuit of its mission, including aeronautics, earth science, astrobiology and notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particularly space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement and the 2012 team has expanded the use of synthetic biology to estimate the potential for life in the clouds of other planets (http://2012.igem.org/Team:Stanford-Brown; http://www.calacademy.org/sciencetoday/igem-competition/). More recent projects from the Stanford-Brown team have expanded our ideas of how synthetic biology can aid NASA's missions from "Synthetic BioCommunication" (http://2013.igem.org/Team:Stanford-Brown) to a "Biodegradable UAS (drone)" in collaboration with Spelman College (http://2014.igem.org/Team:StanfordBrownSpelman#SBS%20iGEM) and most recently, "Self-Folding Origami" (http://2015.igem.org/Team:Stanford-Brown), the winner of the 2015 award for Manufacturing.

FUSE: a profit maximization approach for functional summarization of biological networks.

Science.gov (United States)

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes; Yu, Hanry

2012-03-21

The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

Understanding the Biological Roles of Pectins in Plants through Physiological and Functional Characterizations of Plant and Fungal Mutants

DEFF Research Database (Denmark)

Stranne, Maria

The plant cell wall is a dynamic structure and it is involved in regulating a number of physiological features of plants such as physical strength, growth, cell differentiation, intercellular communication, water movement and defense responses. Pectins constitute a major class of plant cell wall...... polysaccharides and consist of backbones rich in galacturonic acids, which are decorated with a range of functional groups including acetyl esters and arabinan sidechains. Although much effort has been made to uncover biological functions of pectins in plants and remarkable progresses have taken place, many...... aspects remain elusive. Studies described in this thesis aimed at gaining new insights into the biological roles of pectin acetylation and arabinosylation in the model plant Arabidopsis thaliana. The thesis consists of four chapters: physiological characterization of cell wall mutants affected in cell...

Synthetic Biology: Applications in the Food Sector.

Science.gov (United States)

Tyagi, Ashish; Kumar, Ashwani; Aparna, S V; Mallappa, Rashmi H; Grover, Sunita; Batish, Virender Kumar

2016-08-17

Synthetic biology also termed as "genomic alchemy" represents a powerful area of science that is based on the convergence of biological sciences with systems engineering. It has been fittingly described as "moving from reading the genetic code to writing it" as it focuses on building, modeling, designing and fabricating novel biological systems using customized gene components that result in artificially created genetic circuitry. The scientifically compelling idea of the technological manipulation of life has been advocated since long time. Realization of this idea has gained momentum with development of high speed automation and the falling cost of gene sequencing and synthesis following the completion of the human genome project. Synthetic biology will certainly be instrumental in shaping the development of varying areas ranging from biomedicine, biopharmaceuticals, chemical production, food and dairy quality monitoring, packaging, and storage of food and dairy products, bioremediation and bioenergy production, etc. However, potential dangers of using synthetic life forms have to be acknowledged and adoption of policies by the scientific community to ensure safe practice while making important advancements in the ever expanding field of synthetic biology is to be fully supported and implemented.

History of chemical and biological warfare agents

International Nuclear Information System (INIS)

Szinicz, L.

2005-01-01

Chemical and biological warfare agents constitute a low-probability, but high-impact risk both to the military and to the civilian population. The use of hazardous materials of chemical or biological origin as weapons and for homicide has been documented since ancient times. The first use of chemicals in terms of weapons of mass destruction goes back to World War I, when on April 22, 1915 large amounts of chlorine were released by German military forces at Ypres, Belgium. Until around the 1970s of the 20th century, the awareness of the threat by chemical and biological agents had been mainly confined to the military sector. In the following time, the development of increasing range delivery systems by chemical and biological agents possessors sensitised public attention to the threat emanating from these agents. Their proliferation to the terrorists field during the 1990s with the expanding scale and globalisation of terrorist attacks suggested that these agents are becoming an increasing threat to the whole world community. The following article gives a condensed overview on the history of use and development of the more prominent chemical and biological warfare agents

History of chemical and biological warfare agents.

Science.gov (United States)

Szinicz, L

2005-10-30

Chemical and biological warfare agents constitute a low-probability, but high-impact risk both to the military and to the civilian population. The use of hazardous materials of chemical or biological origin as weapons and for homicide has been documented since ancient times. The first use of chemicals in terms of weapons of mass destruction goes back to World War I, when on April 22, 1915 large amounts of chlorine were released by German military forces at Ypres, Belgium. Until around the 1970s of the 20th century, the awareness of the threat by chemical and biological agents had been mainly confined to the military sector. In the following time, the development of increasing range delivery systems by chemical and biological agents possessors sensitised public attention to the threat emanating from these agents. Their proliferation to the terrorists field during the 1990s with the expanding scale and globalisation of terrorist attacks suggested that these agents are becoming an increasing threat to the whole world community. The following article gives a condensed overview on the history of use and development of the more prominent chemical and biological warfare agents.

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

Science.gov (United States)

Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

2015-07-06

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.

Science.gov (United States)

Gunetti, Monica; Noghero, Alessio; Molla, Fabiola; Staszewsky, Lidia Irene; de Angelis, Noeleen; Soldo, Annarita; Russo, Ilaria; Errichiello, Edoardo; Frasson, Chiara; Rustichelli, Deborah; Ferrero, Ivana; Gualandris, Anna; Berger, Massimo; Geuna, Massimo; Scacciatella, Paolo; Basso, Giuseppe; Marra, Sebastiano; Bussolino, Federico; Latini, Roberto; Fagioli, Franca

2011-10-01

Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34(+)-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34(+) cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34(+) cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14(+) subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Our data suggest that combining basal and expanded BM-derived CD34(+) cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

How biological soil crusts became recognized as a functional unit: a selective history

Science.gov (United States)

Lange, Otto L.; Belnap, Jayne

2016-01-01

It is surprising that despite the world-wide distribution and general importance of biological soil crusts (biocrusts), scientific recognition and functional analysis of these communities is a relatively young field of science. In this chapter, we sketch the historical lines that led to the recognition of biocrusts as a community with important ecosystem functions. The idea of biocrusts as a functional ecological community has come from two main scientific branches: botany and soil science. For centuries, botanists have long recognized that multiple organisms colonize the soil surface in the open and often dry areas occurring between vascular plants. Much later, after the initial taxonomic and phyto-sociological descriptions were made, soil scientists and agronomists observed that these surface organisms interacted with soils in ways that changed the soil structure. In the 1970’s, research on these communities as ecological units that played an important functional role in drylands began in earnest, and these studies have continued to this day. Here, we trace the history of these studies from the distant past until 1990, when biocrusts became well-known to scientists and the public.

Optimization of polysaccharides extraction from watermelon rinds: Structure, functional and biological activities.

Science.gov (United States)

Romdhane, Molka Ben; Haddar, Anissa; Ghazala, Imen; Jeddou, Khawla Ben; Helbert, Claire Boisset; Ellouz-Chaabouni, Semia

2017-02-01

In the present work, optimization of hot water extraction, structural characteristics, functional properties, and biological activities of polysaccharides extracted from watermelon rinds (WMRP) were investigated. The physicochemical characteristics and the monosaccharide composition of these polysaccharides were then determined using chemical composition analysis, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and gas chromatography-flame ionization detection (GC-FID). SEM images showed that extracted polysaccharides had a rough surface with many cavities. GC-FID results proved that galactose was the dominant sugar in the extracted polysaccharides, followed by arabinose, glucose, galacturonic acid, rhamnose, mannose, xylose and traces of glucuronic acid. The findings revealed that WMRP displayed excellent antihypertensive and antioxidant activities. Those polysaccharides had also a protection effect against hydroxyl radical-induced DNA damage. Functional properties of extracted polysaccharides were also evaluated. WMRP showed good interfacial dose-dependent proprieties. Overall, the results suggested that WMRP presents a promising natural source of antioxidants and antihypertensive agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Expanding Universe: Dark Energy

Energy Technology Data Exchange (ETDEWEB)

Lincoln, Don [Fermilab; Nord, Brian [Fermilab

2014-09-01

In 1998, observations of distant supernovae led physicists that not only was the universe expanding, but the expansion was speeding up. In this article, we describe the evidence for an expanding universe and describe what physicists and cosmologists have learned in the intervening years. The target audience for this article is high school physics teachers and college physics professors at teaching institutions.

Connecting Structure-Property and Structure-Function Relationships across the Disciplines of Chemistry and Biology: Exploring Student Perceptions

Science.gov (United States)

Kohn, Kathryn P.; Underwood, Sonia M.; Cooper, Melanie M.

2018-01-01

While many university students take science courses in multiple disciplines, little is known about how they perceive common concepts from different disciplinary perspectives. Structure-property and structure-function relationships have long been considered important explanatory concepts in the disciplines of chemistry and biology, respectively.…

Chorusing, synchrony and the evolutionary functions of rhythm

Directory of Open Access Journals (Sweden)

Andrea eRavignani

2014-10-01

Full Text Available A central goal of biomusicology is to understand the biological basis of human musicality. One approach to this problem has been to compare core components of human musicality (relative pitch perception, entrainment, etc. with similar capacities in other animal species. Here we extend and clarify this comparative approach with respect to rhythm. First, whereas most comparisons between human music and animal acoustic behavior have focused on spectral properties (melody and harmony, we argue for the central importance of temporal properties, and propose that this domain is ripe for further comparative research. Second, whereas most rhythm research in non-human animals has examined animal timing in isolation, we consider how chorusing dynamics can shape individual timing, as in human music and dance, making group behavior key to understand the adaptive functions of rhythm. To illustrate the interdependence between individual and chorusing dynamics, we present a computational model of chorusing agents relating individual call timing with synchronous group behavior. Third, we distinguish and clarify mechanistic and functional explanations of rhythmic phenomena, often conflated in the literature, arguing that this distinction is key for understanding the evolution of musicality. Fourth, we expand biomusicological discussions beyond the species typically considered, providing an overview of chorusing and rhythmic behavior across a broad range of taxa (orthopterans, fireflies, frogs, birds, and primates. Finally, we propose an Evolving Signal Timing hypothesis, suggesting that similarities between timing abilities in biological species will be based on comparable chorusing behaviors. We conclude that the comparative study of chorusing species can provide important insights into the adaptive function(s of rhythmic behavior in our proto-musical primate ancestors, and thus inform our understanding of the biology and evolution of rhythm in human music and

Chorusing, synchrony, and the evolutionary functions of rhythm.

Science.gov (United States)

Ravignani, Andrea; Bowling, Daniel L; Fitch, W Tecumseh

2014-01-01

A central goal of biomusicology is to understand the biological basis of human musicality. One approach to this problem has been to compare core components of human musicality (relative pitch perception, entrainment, etc.) with similar capacities in other animal species. Here we extend and clarify this comparative approach with respect to rhythm. First, whereas most comparisons between human music and animal acoustic behavior have focused on spectral properties (melody and harmony), we argue for the central importance of temporal properties, and propose that this domain is ripe for further comparative research. Second, whereas most rhythm research in non-human animals has examined animal timing in isolation, we consider how chorusing dynamics can shape individual timing, as in human music and dance, arguing that group behavior is key to understanding the adaptive functions of rhythm. To illustrate the interdependence between individual and chorusing dynamics, we present a computational model of chorusing agents relating individual call timing with synchronous group behavior. Third, we distinguish and clarify mechanistic and functional explanations of rhythmic phenomena, often conflated in the literature, arguing that this distinction is key for understanding the evolution of musicality. Fourth, we expand biomusicological discussions beyond the species typically considered, providing an overview of chorusing and rhythmic behavior across a broad range of taxa (orthopterans, fireflies, frogs, birds, and primates). Finally, we propose an "Evolving Signal Timing" hypothesis, suggesting that similarities between timing abilities in biological species will be based on comparable chorusing behaviors. We conclude that the comparative study of chorusing species can provide important insights into the adaptive function(s) of rhythmic behavior in our "proto-musical" primate ancestors, and thus inform our understanding of the biology and evolution of rhythm in human music and

Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.

Science.gov (United States)

Davydyan, Garri

2015-12-01

The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements ( TrA  > 0) and also positive values of matrix determinant ( detA  > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what

Antibiotic resistance shaping multilevel population biology of bacteria

Directory of Open Access Journals (Sweden)

Fernando eBaquero

2013-03-01

Full Text Available Antibiotics have natural functions, mostly involving cell-to-cell signalling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent population biologies. Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of clinical antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge

The nuclear envelope from basic biology to therapy.

Science.gov (United States)

Worman, Howard J; Foisner, Roland

2010-02-01

The nuclear envelope has long been a focus of basic research for a highly specialized group of cell biologists. More recently, an expanding group of scientists and physicians have developed a keen interest in the nuclear envelope since mutations in the genes encoding lamins and associated proteins have been shown to cause a diverse range of human diseases often called laminopathies or nuclear envelopathies. Most of these diseases have tissue-selective phenotypes, suggesting that the nuclear envelope must function in cell-type- and developmental-stage-specific processes such as chromatin organization, regulation of gene expression, controlled nucleocytoplasmic transport and response to stress in metazoans. On 22-23 April 2009, Professor Christopher Hutchison organized the 4th British Nuclear Envelope Disease and Chromatin Organization meeting at the College of St Hild and St Bede at Durham University, sponsored by the Biochemical Society. In attendance were investigators with one common interest, the nuclear envelope, but with diverse expertise and training in animal and plant cell biology, genetics, developmental biology and medicine. We were each honoured to be keynote speakers. This issue of Biochemical Society Transactions contains papers written by some of the presenters at this scientifically exciting meeting, held in a bucolic setting where the food was tasty and the wine flowed freely. Perhaps at the end of this excellent meeting more questions were raised than answered, which will stimulate future research. However, what became clear is that the nuclear envelope is a cellular structure with critical functions in addition to its traditional role as a barrier separating the nuclear and cytoplasmic compartments in interphase eukaryotic cells.

A Tricky Trait: Applying the Fruits of the “Function Debate” in the Philosophy of Biology to the “Venom Debate” in the Science of Toxinology

Science.gov (United States)

Jackson, Timothy N. W.; Fry, Bryan G.

2016-01-01

The “function debate” in the philosophy of biology and the “venom debate” in the science of toxinology are conceptually related. Venom systems are complex multifunctional traits that have evolved independently numerous times throughout the animal kingdom. No single concept of function, amongst those popularly defended, appears adequate to describe these systems in all their evolutionary contexts and extant variations. As such, a pluralistic view of function, previously defended by some philosophers of biology, is most appropriate. Venom systems, like many other functional traits, exist in nature as points on a continuum and the boundaries between “venomous” and “non-venomous” species may not always be clearly defined. This paper includes a brief overview of the concept of function, followed by in-depth discussion of its application to venom systems. A sound understanding of function may aid in moving the venom debate forward. Similarly, consideration of a complex functional trait such as venom may be of interest to philosophers of biology. PMID:27618098

A Tricky Trait: Applying the Fruits of the “Function Debate” in the Philosophy of Biology to the “Venom Debate” in the Science of Toxinology

Directory of Open Access Journals (Sweden)

Timothy N. W. Jackson

2016-09-01

Full Text Available The “function debate” in the philosophy of biology and the “venom debate” in the science of toxinology are conceptually related. Venom systems are complex multifunctional traits that have evolved independently numerous times throughout the animal kingdom. No single concept of function, amongst those popularly defended, appears adequate to describe these systems in all their evolutionary contexts and extant variations. As such, a pluralistic view of function, previously defended by some philosophers of biology, is most appropriate. Venom systems, like many other functional traits, exist in nature as points on a continuum and the boundaries between “venomous” and “non-venomous” species may not always be clearly defined. This paper includes a brief overview of the concept of function, followed by in-depth discussion of its application to venom systems. A sound understanding of function may aid in moving the venom debate forward. Similarly, consideration of a complex functional trait such as venom may be of interest to philosophers of biology.

Functional transferred DNA within extracellular vesicles

Energy Technology Data Exchange (ETDEWEB)

Cai, Jin [Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province (China); Wu, Gengze [Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Jose, Pedro A. [Division of Nephrology, Department of Medicine and Physiology, University of Maryland, School of Medicine, Baltimore, MD 21201 (United States); Zeng, Chunyu, E-mail: Chunyuzeng01@163.com [Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China)

2016-11-15

Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs. Specific interaction of EVs with susceptible recipients performs the uptake of EVs into the target cells, discharging their cargo including nuclear and cytoplasmic macromolecules into the cytosol. These findings expand the nucleic acid content of EVs to include increased levels of specific DNA. Thus, EVs contain a repertoire of genetic information available for horizontal gene transfer and potential use as blood biomarkers for cancer and atherosclerosis. In this review, the focus is on the characteristics, biological functions, and roles in diseases of DNA within EVs. - Highlights: • This review is focused on the DNA within EVs including its characteristics, biological functions, and roles in diseases. • It is clear that DNA within EVs might have important physiological and pathological roles in various diseases. • Knowledge in this area may provides us alternative methods for disease diagnosis or therapy in the future.

Functional transferred DNA within extracellular vesicles

International Nuclear Information System (INIS)

Cai, Jin; Wu, Gengze; Jose, Pedro A.; Zeng, Chunyu

2016-01-01

Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs. Specific interaction of EVs with susceptible recipients performs the uptake of EVs into the target cells, discharging their cargo including nuclear and cytoplasmic macromolecules into the cytosol. These findings expand the nucleic acid content of EVs to include increased levels of specific DNA. Thus, EVs contain a repertoire of genetic information available for horizontal gene transfer and potential use as blood biomarkers for cancer and atherosclerosis. In this review, the focus is on the characteristics, biological functions, and roles in diseases of DNA within EVs. - Highlights: • This review is focused on the DNA within EVs including its characteristics, biological functions, and roles in diseases. • It is clear that DNA within EVs might have important physiological and pathological roles in various diseases. • Knowledge in this area may provides us alternative methods for disease diagnosis or therapy in the future.

Screw expander for light duty diesel engines

Science.gov (United States)

1983-01-01

Preliminary selection and sizing of a positive displacement screw compressor-expander subsystem for a light-duty adiabatic diesel engine; development of a mathematical model to describe overall efficiencies for the screw compressor and expander; simulation of operation to establish overall efficiency for a range of design parameters and at given engine operating points; simulation to establish potential net power output at light-duty diesel operating points; analytical determination of mass moments of inertia for the rotors and inertia of the compressor-expander subsystem; and preparation of engineering layout drawings of the compressor and expander are discussed. As a result of this work, it was concluded that the screw compressor and expander designed for light-duty diesel engine applications are viable alternatives to turbo-compound systems, with acceptable efficiencies for both units, and only a moderate effect on the transient response.

Green leaf volatiles: biosynthesis, biological functions and their applications in biotechnology.

Science.gov (United States)

ul Hassan, Muhammad Naeem; Zainal, Zamri; Ismail, Ismanizan

2015-08-01

Plants have evolved numerous constitutive and inducible defence mechanisms to cope with biotic and abiotic stresses. These stresses induce the expression of various genes to activate defence-related pathways that result in the release of defence chemicals. One of these defence mechanisms is the oxylipin pathway, which produces jasmonates, divinylethers and green leaf volatiles (GLVs) through the peroxidation of polyunsaturated fatty acids (PUFAs). GLVs have recently emerged as key players in plant defence, plant-plant interactions and plant-insect interactions. Some GLVs inhibit the growth and propagation of plant pathogens, including bacteria, viruses and fungi. In certain cases, GLVs released from plants under herbivore attack can serve as aerial messengers to neighbouring plants and to attract parasitic or parasitoid enemies of the herbivores. The plants that perceive these volatile signals are primed and can then adapt in preparation for the upcoming challenges. Due to their 'green note' odour, GLVs impart aromas and flavours to many natural foods, such as vegetables and fruits, and therefore, they can be exploited in industrial biotechnology. The aim of this study was to review the progress and recent developments in research on the oxylipin pathway, with a specific focus on the biosynthesis and biological functions of GLVs and their applications in industrial biotechnology. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

BioCore Guide: A Tool for Interpreting the Core Concepts of Vision and Change for Biology Majors.

Science.gov (United States)

Brownell, Sara E; Freeman, Scott; Wenderoth, Mary Pat; Crowe, Alison J

2014-01-01

Vision and Change in Undergraduate Biology Education outlined five core concepts intended to guide undergraduate biology education: 1) evolution; 2) structure and function; 3) information flow, exchange, and storage; 4) pathways and transformations of energy and matter; and 5) systems. We have taken these general recommendations and created a Vision and Change BioCore Guide-a set of general principles and specific statements that expand upon the core concepts, creating a framework that biology departments can use to align with the goals of Vision and Change. We used a grassroots approach to generate the BioCore Guide, beginning with faculty ideas as the basis for an iterative process that incorporated feedback from more than 240 biologists and biology educators at a diverse range of academic institutions throughout the United States. The final validation step in this process demonstrated strong national consensus, with more than 90% of respondents agreeing with the importance and scientific accuracy of the statements. It is our hope that the BioCore Guide will serve as an agent of change for biology departments as we move toward transforming undergraduate biology education. © 2014 S. E. Brownell et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Oversight of High-Containment Biological Laboratories: Issues for Congress

Science.gov (United States)

2009-05-04

Laboratories: Issues for Congress Congressional Research Service 14 Industry and Non-Profit Laboratories Private sector companies and non-profit...resources for these endeavors. Whether public or private sector , high-containment laboratories are planned and designed to minimize the possibility of... equine encephalitis, and yellow fever. Some of the pathogens that cause these diseases have been considered as biological weapons.104 Expanding the number

Marine Carotenoids: Biological Functions and Commercial Applications

NARCIS (Netherlands)

Vilchez, C.; Forján, E.; Cuaresma, M.; Bédmar, F.; Garbayo, I.; Vega, J.M.

2011-01-01

Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological

Expanding the toolbox for studying the biological responses of individual fish to hydropower infrastructure and operating strategies

International Nuclear Information System (INIS)

Hasler, C.T.; Cooke, S.J.; Patterson, D.A.

2009-01-01

Hydropower infrastructure and the operational strategies used by power utilities have the potential to change local aquatic environments. However, few studies have evaluated sub-organismal responses such as physiological consequences of individual fish to fluctuating flows or hydropower infrastructure such as fishways or turbines. Rather than review the impacts of hydropower on fish, this paper detailed the behavioural, energetic, genomic, molecular, forensic, isotopic, and physiological tools available for studying sub-organismal responses of fish to hydropower infrastructure and operating procedures with a critical assessment of their benefits and limitations. A brief summary of the current state of knowledge regarding the 12 types of tools was provided along with their usefulness in fisheries science and environmental management. The benefits and limitations of using these techniques for evaluating hydropower impacts on fish and fish habitat were discussed. Two case studies were presented to demonstrate how the inclusion of individual-based information into hydropower research has helped to improve the understanding of complex fish and hydropower issues. Practitioners can use the expanded toolbox to assess fishway performance, migration delays, and fish responses to fluctuating flows through a mechanistic approach. These tools are also relevant for evaluating other anthropogenic impacts such as water withdrawal for irrigation or drinking water, habitat alteration, and fisheries interactions. The expanded toolbox can contribute to a more sustainable hydropower industry by providing regulators with tools for making informed decisions and evaluating compliance issues. 150 refs., 1 tab., 4 figs

Recent advances of molecular toolbox construction expand Pichia pastoris in synthetic biology applications.

Science.gov (United States)

Kang, Zhen; Huang, Hao; Zhang, Yunfeng; Du, Guocheng; Chen, Jian

2017-01-01

Pichia pastoris: (reclassified as Komagataella phaffii), a methylotrophic yeast strain has been widely used for heterologous protein production because of its unique advantages, such as readily achievable high-density fermentation, tractable genetic modifications and typical eukaryotic post-translational modifications. More recently, P. pastoris as a metabolic pathway engineering platform has also gained much attention. In this mini-review, we addressed recent advances of molecular toolboxes, including synthetic promoters, signal peptides, and genome engineering tools that established for P. pastoris. Furthermore, the applications of P. pastoris towards synthetic biology were also discussed and prospected especially in the context of genome-scale metabolic pathway analysis.

Coral Reef Health Indices versus the Biological, Ecological and Functional Diversity of Fish and Coral Assemblages in the Caribbean Sea.

Science.gov (United States)

Díaz-Pérez, Leopoldo; Rodríguez-Zaragoza, Fabián Alejandro; Ortiz, Marco; Cupul-Magaña, Amílcar Leví; Carriquiry, Jose D; Ríos-Jara, Eduardo; Rodríguez-Troncoso, Alma Paola; García-Rivas, María Del Carmen

2016-01-01

This study evaluated the relationship between the indices known as the Reef Health Index (RHI) and two-dimensional Coral Health Index (2D-CHI) and different representative metrics of biological, ecological and functional diversity of fish and corals in 101 reef sites located across seven zones in the western Caribbean Sea. Species richness and average taxonomic distinctness were used to asses biological estimation; while ecological diversity was evaluated with the indices of Shannon diversity and Pielou´s evenness, as well as by taxonomic diversity and distinctness. Functional diversity considered the number of functional groups, the Shannon diversity and the functional Pielou´s evenness. According to the RHI, 57.15% of the zones were classified as presenting a "poor" health grade, while 42.85% were in "critical" grade. Based on the 2D-CHI, 28.5% of the zones were in "degraded" condition and 71.5% were "very degraded". Differences in fish and coral diversity among sites and zones were demonstrated using permutational ANOVAs. Differences between the two health indices (RHI and 2D-CHI) and some indices of biological, ecological and functional diversity of fish and corals were observed; however, only the RHI showed a correlation between the health grades and the species and functional group richness of fish at the scale of sites, and with the species and functional group richness and Shannon diversity of the fish assemblages at the scale of zones. None of the health indices were related to the metrics analyzed for the coral diversity. In general, our study suggests that the estimation of health indices should be complemented with classic community indices, or should at least include diversity indices of fish and corals, in order to improve the accuracy of the estimated health status of coral reefs in the western Caribbean Sea.

Aminotryptophan-containing barstar: structure--function tradeoff in protein design and engineering with an expanded genetic code.

Science.gov (United States)

Rubini, Marina; Lepthien, Sandra; Golbik, Ralph; Budisa, Nediljko

2006-07-01

The indole ring of the canonical amino acid tryptophan (Trp) possesses distinguished features, such as sterical bulk, hydrophobicity and the nitrogen atom which is capable of acting as a hydrogen bond donor. The introduction of an amino group into the indole moiety of Trp yields the structural analogs 4-aminotryptophan ((4-NH(2))Trp) and 5-aminotryptophan ((5-NH(2))Trp). Their hydrophobicity and spectral properties are substantially different when compared to those of Trp. They resemble the purine bases of DNA and share their capacity for pH-sensitive intramolecular charge transfer. The Trp --> aminotryptophan substitution in proteins during ribosomal translation is expected to result in related protein variants that acquire these features. These expectations have been fulfilled by incorporating (4-NH(2))Trp and (5-NH(2))Trp into barstar, an intracellular inhibitor of the ribonuclease barnase from Bacillus amyloliquefaciens. The crystal structure of (4-NH(2))Trp-barstar is similar to that of the parent protein, whereas its spectral and thermodynamic behavior is found to be remarkably different. The T(m) value of (4-NH(2))Trp- and (5-NH(2))Trp-barstar is lowered by about 20 degrees Celsius, and they exhibit a strongly reduced unfolding cooperativity and substantial loss of free energy in folding. Furthermore, folding kinetic study of (4-NH(2))Trp-barstar revealed that the denatured state is even preferred over native one. The combination of structural and thermodynamic analyses clearly shows how structures of substituted barstar display a typical structure-function tradeoff: the acquirement of unique pH-sensitive charge transfer as a novel function is achieved at the expense of protein stability. These findings provide a new insight into the evolution of the amino acid repertoire of the universal genetic code and highlight possible problems regarding protein engineering and design by using an expanded genetic code.

FUSE: a profit maximization approach for functional summarization of biological networks

Directory of Open Access Journals (Sweden)

Seah Boon-Siew

2012-03-01

Full Text Available Abstract Background The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL principle to maximize information gain of the summary graph while satisfying the level of detail constraint. Results We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. Conclusion By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

Fostering synergy between cell biology and systems biology.

Science.gov (United States)

Eddy, James A; Funk, Cory C; Price, Nathan D

2015-08-01

In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Flame Speed and Self-Similar Propagation of Expanding Turbulent Premixed Flames

Science.gov (United States)

Chaudhuri, Swetaprovo; Wu, Fujia; Zhu, Delin; Law, Chung K.

2012-01-01

In this Letter we present turbulent flame speeds and their scaling from experimental measurements on constant-pressure, unity Lewis number expanding turbulent flames, propagating in nearly homogeneous isotropic turbulence in a dual-chamber, fan-stirred vessel. It is found that the normalized turbulent flame speed as a function of the average radius scales as a turbulent Reynolds number to the one-half power, where the average radius is the length scale and the thermal diffusivity is the transport property, thus showing self-similar propagation. Utilizing this dependence it is found that the turbulent flame speeds from the present expanding flames and those from the Bunsen geometry in the literature can be unified by a turbulent Reynolds number based on flame length scales using recent theoretical results obtained by spectral closure of the transformed G equation.

Double-layer ion acceleration triggered by ion magnetization in expanding radiofrequency plasma sources

International Nuclear Information System (INIS)

Takahashi, Kazunori; Charles, Christine; Boswell, Rod W.; Fujiwara, Tamiya

2010-01-01

Ion energy distribution functions downstream of the source exit in magnetically expanding low-pressure plasmas are experimentally investigated for four source tube diameters ranging from about 5 to 15 cm. The magnetic-field threshold corresponding to a transition from a simple expanding plasma to a double layer-containing plasma is observed to increase with a decrease in the source tube diameter. The results demonstrate that for the four geometries, the double layer and the accelerated ion beam form when the ion Larmour radius in the source becomes smaller than the source tube radius, i.e., when the ions become magnetized in the source tube.

Michael Levitt and Computational Biology

Science.gov (United States)

dropdown arrow Site Map A-Z Index Menu Synopsis Michael Levitt and Computational Biology Resources with Michael Levitt, PhD, professor of structural biology at the Stanford University School of Medicine, has function. ... Levitt's early work pioneered computational structural biology, which helped to predict

A-coupled-expanding and distributional chaos

International Nuclear Information System (INIS)

Kim, Cholsan; Ju, Hyonhui; Chen, Minghao; Raith, Peter

2015-01-01

The concept of A-coupled-expanding maps is one of the more natural and useful ideas generalized from the horseshoe map which is commonly known as a criterion of chaos. It is well known that distributional chaos is one of the concepts which reflect strong chaotic behavior. In this paper, we focus on the relationship between A-coupled-expanding and distributional chaos. We prove two theorems which give sufficient conditions for a strictly A-coupled-expanding map to be distributionally chaotic in the senses of two kinds, where A is an m × m irreducible transition matrix

Flame surface statistics of constant-pressure turbulent expanding premixed flames

Science.gov (United States)

Saha, Abhishek; Chaudhuri, Swetaprovo; Law, Chung K.

2014-04-01

In this paper we investigate the local flame surface statistics of constant-pressure turbulent expanding flames. First the statistics of local length ratio is experimentally determined from high-speed planar Mie scattering images of spherically expanding flames, with the length ratio on the measurement plane, at predefined equiangular sectors, defined as the ratio of the actual flame length to the length of a circular-arc of radius equal to the average radius of the flame. Assuming isotropic distribution of such flame segments we then convolute suitable forms of the length-ratio probability distribution functions (pdfs) to arrive at the corresponding area-ratio pdfs. It is found that both the length ratio and area ratio pdfs are near log-normally distributed and shows self-similar behavior with increasing radius. Near log-normality and rather intermittent behavior of the flame-length ratio suggests similarity with dissipation rate quantities which stimulates multifractal analysis.

Characterization of the stability and bio-functionality of tethered proteins on bioengineered scaffolds: implications for stem cell biology and tissue repair.

Science.gov (United States)

Wang, Ting-Yi; Bruggeman, Kiara A F; Sheean, Rebecca K; Turner, Bradley J; Nisbet, David R; Parish, Clare L

2014-05-23

Various engineering applications have been utilized to deliver molecules and compounds in both innate and biological settings. In the context of biological applications, the timely delivery of molecules can be critical for cellular and organ function. As such, previous studies have demonstrated the superiority of long-term protein delivery, by way of protein tethering onto bioengineered scaffolds, compared with conventional delivery of soluble protein in vitro and in vivo. Despite such benefits little knowledge exists regarding the stability, release kinetics, longevity, activation of intracellular pathway, and functionality of these proteins over time. By way of example, here we examined the stability, degradation and functionality of a protein, glial-derived neurotrophic factor (GDNF), which is known to influence neuronal survival, differentiation, and neurite morphogenesis. Enzyme-linked immunosorbent assays (ELISA) revealed that GDNF, covalently tethered onto polycaprolactone (PCL) electrospun nanofibrous scaffolds, remained present on the scaffold surface for 120 days, with no evidence of protein leaching or degradation. The tethered GDNF protein remained functional and capable of activating downstream signaling cascades, as revealed by its capacity to phosphorylate intracellular Erk in a neural cell line. Furthermore, immobilization of GDNF protein promoted cell survival and differentiation in culture at both 3 and 7 days, further validating prolonged functionality of the protein, well beyond the minutes to hours timeframe observed for soluble proteins under the same culture conditions. This study provides important evidence of the stability and functionality kinetics of tethered molecules. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Feasibility of using bulk metallic glass for self-expandable stent applications.

Science.gov (United States)

Praveen Kumar, Gideon; Jafary-Zadeh, Mehdi; Tavakoli, Rouhollah; Cui, Fangsen

2017-10-01

Self-expandable stents are widely used to restore blood flow in a diseased artery segment by keeping the artery open after angioplasty. Despite the prevalent use of conventional crystalline metallic alloys, for example, nitinol, to construct self-expandable stents, new biomaterials such as bulk metallic glasses (BMGs) are being actively pursued to improve stent performance. Here, we conducted a series of analyses including finite element analysis and molecular dynamics simulations to investigate the feasibility of using a prototypical Zr-based BMG for self-expandable stent applications. We model stent crimping of several designs for different percutaneous applications. Our results indicate that BMG-based stents with diamond-shaped crowns suffer from severe localization of plastic deformation and abrupt failure during crimping. As a possible solution, we further illustrate that such abrupt failure could be avoided in BMG-based stents without diamond shape crowns. This work would open a new horizon for a quest toward exploiting superior mechanical and functional properties of metallic glasses to design future stents. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1874-1882, 2017. © 2016 Wiley Periodicals, Inc.

Biological functioning of PAH-polluted and thermal desorption-treated soils assessed by fauna and microbial bioindicators.

Science.gov (United States)

Cébron, Aurélie; Cortet, Jérôme; Criquet, Stéven; Biaz, Asmaa; Calvert, Virgile; Caupert, Cécile; Pernin, Céline; Leyval, Corinne

2011-11-01

A large number of soil bioindicators were used to assess biological diversity and activity in soil polluted with polycyclic aromatic hydrocarbons (PAHs) and the same soil after thermal desorption (TD) treatment. Abundance and biodiversity of bacteria, fungi, protozoa, nematodes and microarthropods, as well as functional parameters such as enzymatic activities and soil respiration, were assessed during a two year period of in situ monitoring. We investigated the influence of vegetation (spontaneous vegetation and Medicago sativa) and TD treatment on biological functioning. Multivariate analysis was performed to analyze the whole data set. A principal response curve (PRC) technique was used to evaluate the different treatments (various vegetation and contaminated vs. TD soil) contrasted with control (bare) soil over time. Our results indicated the value of using a number of complementary bioindicators, describing both diversity and functions, to assess the influence of vegetation on soil and discriminate polluted from thermal desorption (TD)-treated soil. Plants had an influence on the abundance and activity of all organisms examined in our study, favoring the whole trophic chain development. However, although TD-treated soil had a high abundance and diversity of microorganisms and fauna, enzymatic activities were weak because of the strong physical and chemical modifications of this soil. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

BiologicalNetworks 2.0 - an integrative view of genome biology data

Directory of Open Access Journals (Sweden)

Ponomarenko Julia

2010-12-01

Full Text Available Abstract Background A significant problem in the study of mechanisms of an organism's development is the elucidation of interrelated factors which are making an impact on the different levels of the organism, such as genes, biological molecules, cells, and cell systems. Numerous sources of heterogeneous data which exist for these subsystems are still not integrated sufficiently enough to give researchers a straightforward opportunity to analyze them together in the same frame of study. Systematic application of data integration methods is also hampered by a multitude of such factors as the orthogonal nature of the integrated data and naming problems. Results Here we report on a new version of BiologicalNetworks, a research environment for the integral visualization and analysis of heterogeneous biological data. BiologicalNetworks can be queried for properties of thousands of different types of biological entities (genes/proteins, promoters, COGs, pathways, binding sites, and other and their relations (interactions, co-expression, co-citations, and other. The system includes the build-pathways infrastructure for molecular interactions/relations and module discovery in high-throughput experiments. Also implemented in BiologicalNetworks are the Integrated Genome Viewer and Comparative Genomics Browser applications, which allow for the search and analysis of gene regulatory regions and their conservation in multiple species in conjunction with molecular pathways/networks, experimental data and functional annotations. Conclusions The new release of BiologicalNetworks together with its back-end database introduces extensive functionality for a more efficient integrated multi-level analysis of microarray, sequence, regulatory, and other data. BiologicalNetworks is freely available at http://www.biologicalnetworks.org.

Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors.

Science.gov (United States)

Chandran, Priya; Le, Yevgeniya; Li, Yuhua; Sabloff, Mitchell; Mehic, Jelica; Rosu-Myles, Michael; Allan, David S

2015-04-01

The bone marrow microenvironment may be permissive to the emergence and progression of acute myeloid leukemia (AML). Studying interactions between the microenvironment and leukemia cells should provide new insight for therapeutic advances. Mesenchymal stromal cells (MSCs) are central to the maintenance of the hematopoietic niche. Here we compared the functions and gene expression patterns of MSCs derived from bone marrow aspirates of healthy donors and patients with AML. MSCs expanded from AML patients had heterogeneous morphology and displayed a wide range of proliferation capacity compared to MSCs from healthy controls. The ability of AML-MSCs to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired while the expression of genes associated with maintaining hematopoietic quiescence appeared to be increased in AML-MSCs compared to healthy donors. These results highlight important potential differences in the biologic profile of MSCs from AML patients compared to healthy donors that may contribute to the emergence or progression of leukemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional biology and ecological role of krill in Northern marine ecosystems

DEFF Research Database (Denmark)

Agersted, Mette Dalgaard

Krill is an understudied key group of zooplankton, which transfers energy through the food web by linking lower and higher trophic levels. Furthermore, krill play an important role in the biological pump by transporting carbon out of the euphotic zone to depth by diel vertical migration (DVM...... to be the key factor determining the trophic position of a species, where the largest species had the highest trophic position. The species were feeding on the same food items, which could lead to competition for food. However, there is a difference between the two functional groups, represented by M. norvegica...... for the two dominating species within the fjord, T. inermis and T. raschii. The krill grazed community at this time of year. Yet, the grazing impact was similar to the copepods’, which are normally...

A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

Science.gov (United States)

Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

2016-06-17

Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

Stability of expanded plasma focus

International Nuclear Information System (INIS)

Soliman, H.M.

1994-01-01

In this study, the stabilization of the expanded plasma focus formed by 4.5 kJ plasma focus device of Mather type by magnetic field is presented. The experimental results of the induced axial magnetic field and electric probe measurements of the expanded plasma focus show that, the plasma consists of three plasmoids, electron temperature measurements off the plasmoids at a point close to the muzzle are 26 eV, 30 eV and 27 eV respectively and the electron densities are 6.6 x 10 14 , 6.1 x 10 14 / cm 3 respectively. The presence of external axial magnetic field (B 2 = 1.6 kg) at the mid distance between the breech and the muzzle has a less effect on the stability of expanded focus and it causes a restriction for the plasma motion. the electron temperature of the three plasmoids are found to increase in that case by 23%, 18.5% respectively. When this axial magnetic field is applied at the muzzle end, it leads to a more stable expanded plasma focus which consists mainly of one plasmoid with electron temperature of 39 eV and density of 3.4 x 10 14 / cm 3 . 5 figs

Bottom-up synthetic biology: modular design for making artificial platelets

Science.gov (United States)

Majumder, Sagardip; Liu, Allen P.

2018-01-01

Engineering artificial cells to mimic one or multiple fundamental cell biological functions is an emerging area of synthetic biology. Reconstituting functional modules from biological components in vitro is a challenging yet an important essence of bottom-up synthetic biology. Here we describe the concept of building artificial platelets using bottom-up synthetic biology and the four functional modules that together could enable such an ambitious effort.

Expanding/Extending English: Interdisciplinarity and Internationalism.

Science.gov (United States)

Fleishman, Avrom

1994-01-01

Discusses the recent efforts to expand literary studies into numerous allied fields and the possible effects that such attempts toward interdisciplinarity and internationalism might have. Warns against possible negative consequences of interdisciplinary approaches. Calls for an expanded view of English as a field of study. (HB)

Geothermal ORC Systems Using Large Screw Expanders

OpenAIRE

Biederman, Tim R.; Brasz, Joost J.

2014-01-01

Geothermal ORC Systems using Large Screw Expanders Tim Biederman Cyrq Energy Abstract This paper describes a low-temperature Organic Rankine Cycle Power Recovery system with a screw expander a derivative of developed of Kaishan's line of screw compressors, as its power unit. The screw expander design is a modified version of its existing refrigeration compressor used on water-cooled chillers. Starting the ORC development program with existing refrigeration screw compre...

Teleology then and now: the question of Kant's relevance for contemporary controversies over function in biology.

Science.gov (United States)

Zammito, John

2006-12-01

'Naturalism' is the aspiration of contemporary philosophy of biology, and Kant simply cannot be refashioned into a naturalist. Instead, epistemological 'deflation' was the decisive feature of Kant's treatment of the 'biomedical' science in his day, so it is not surprising that this might attract some philosophers of science to him today. A certain sense of impasse in the contemporary 'function talk' seems to motivate renewed interest in Kant. Kant--drawing on his eighteenth-century predecessors-provided a discerning and powerful characterization of what biologists had to explain in organic form. His difference from the rest is that he opined that it was impossible to explain it. Its 'inscrutability' was intrinsic. The third Critique essentially proposed the reduction of biology to a kind of pre-scientific descriptivism, doomed never to attain authentic scientificity, to have its 'Newton of the blade of grass'. By contrast, for Locke, and a fortiori for Buffon and his followers, 'intrinsic purposiveness' was a fact of the matter about concrete biological phenomena; the features of internal self-regulation were hypotheses arising out of actual research practice. The difference comes most vividly to light once we recognize Kant's distinction of the concept of organism from the concept of life. If biology must conceptualize self-organization as actual in the world, Kant's regulative/constitutive distinction is pointless in practice and the (naturalist) philosophy of biology has urgent work to undertake for which Kant turns out not to be very helpful.

Factors leading to tracheobronchial self-expandable metallic stent fracture.

Science.gov (United States)

Chung, Fu-Tsai; Lin, Shu-Min; Chen, Hao-Cheng; Chou, Chun-Liang; Yu, Chih-Teng; Liu, Chien-Ying; Wang, Chun-Hua; Lin, Horng-Chyuan; Huang, Chien-Da; Kuo, Han-Pin

2008-11-01

This retrospective study was to determine factors that contribute to self-expandable metallic stent fracture in patients with tracheobronchial disease. From 2001 to 2006, 139 patients (age, 62.1 +/- 15.4 years; range, 23-87 years) with benign (n = 62) and malignant (n = 77) tracheobronchial disease received 192 Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents (98 in patients with benign disease and 94 in patients with malignant disease). Seventeen fractured self-expandable metallic stents were found; the incidence was 12.2% (17/139 patients) among patients with tracheobronchial disease. Tortuous airway (odds ratio, 4.06; 95% confidence interval, 1.04-18.34; P = .04) independently predicted self-expandable metallic stent fracture. Most self-expandable metallic stent fractures (64.7%, 11/17) were detected 500 to 1000 days after self-expandable metallic stent implantation. Clinical presentations for patients with fractured self-expandable metallic stents included dyspnea exacerbation (70.6%, 12/17) and cough (23.5%, 4/17). Self-expandable metallic stent fracture is not uncommon in patients with tracheobronchial disease. Tortuous airway is an independent predictor for it. Although management of the fractured self-expandable metallic stent in our study was feasible and safe, self-expandable metallic stents should be restricted to a more select population.

Neutrinos in an expanding Universe

International Nuclear Information System (INIS)

Wigmans, Richard

2015-01-01

The Universe contains several billion neutrinos for each nucleon. In this paper, we follow the history of these relic neutrinos as the Universe expanded. At present, their typical velocity is a few hundred km/s and, therefore, their spectra are affected by gravitational forces. This may have led to a phenomenon that could explain two of todays great mysteries: The large-scale structure of the Universe and the increasing rate at which it expands. (paper)

Structural and Conformational Chemistry from Electrochemical Molecular Machines. Replicating Biological Functions. A Review.

Science.gov (United States)

Otero, Toribio F

2017-12-14

Each constitutive chain of a conducting polymer electrode acts as a reversible multi-step electrochemical molecular motor: reversible reactions drive reversible conformational movements of the chain. The reaction-driven cooperative actuation of those molecular machines generates, or destroys, inside the film the free volume required to lodge/expel balancing counterions and solvent: reactions drive reversible film volume variations, which basic structural components are here identified and quantified from electrochemical responses. The content of the reactive dense gel (chemical molecular machines, ions and water) mimics that of the intracellular matrix in living functional cells. Reaction-driven properties (composition-dependent properties) and devices replicate biological functions and organs. An emerging technological world of soft, wet, reaction-driven, multifunctional and biomimetic devices and the concomitant zoomorphic or anthropomorphic robots is presented. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Light scattering of a Bessel beam by a nucleated biological cell: An eccentric sphere model

Science.gov (United States)

Wang, Jia Jie; Han, Yi Ping; Chang, Jiao Yong; Chen, Zhu Yang

2018-02-01

Within the framework of generalized Lorenz-Mie theory (GLMT), an eccentrically stratified dielectric sphere model illuminated by an arbitrarily incident Bessel beam is applied to investigate the scattering characteristics of a single nucleated biological cell. The Bessel beam propagating in an arbitrary direction is expanded in terms of vector spherical wave functions (VSWFs), where the beam shape coefficients (BSCs) are calculated rigorously in a closed analytical form. The effects of the half-cone angle of Bessel beam, the location of the particle in the beam, the size ratio of nucleus to cell, and the location of the nucleus inside the cell on the scattering properties of a nucleated cell are analyzed. The results provide useful references for optical diagnostic and imaging of particle having nucleated structure.

Glutamic acid decarboxylase-derived epitopes with specific domains expand CD4(+CD25(+ regulatory T cells.

Directory of Open Access Journals (Sweden)

Guojiang Chen

Full Text Available BACKGROUND: CD4(+CD25(+ regulatory T cell (Treg-based immunotherapy is considered a promising regimen for controlling the progression of autoimmune diabetes. In this study, we tested the hypothesis that the therapeutic effects of Tregs in response to the antigenic epitope stimulation depend on the structural properties of the epitopes used. METHODOLOGY/PRINCIPAL FINDINGS: Splenic lymphocytes from nonobese diabetic (NOD mice were stimulated with different glutamic acid decarboxylase (GAD-derived epitopes for 7-10 days and the frequency and function of Tregs was analyzed. We found that, although all expanded Tregs showed suppressive functions in vitro, only p524 (GAD524-538-expanded CD4(+CD25(+ T cells inhibited diabetes development in the co-transfer models, while p509 (GAD509-528- or p530 (GAD530-543-expanded CD4(+CD25(+ T cells had no such effects. Using computer-guided molecular modeling and docking methods, the differences in structural characteristics of these epitopes and the interaction mode (including binding energy and identified domains in the epitopes between the above-mentioned epitopes and MHC class II I-A(g7 were analyzed. The theoretical results showed that the epitope p524, which induced protective Tregs, possessed negative surface-electrostatic potential and bound two chains of MHC class II I-A(g7, while the epitopes p509 and p530 which had no such ability exhibited positive surface-electrostatic potential and bound one chain of I-A(g7. Furthermore, p524 bound to I-A(g7 more stably than p509 and p530. Of importance, we hypothesized and subsequently confirmed experimentally that the epitope (GAD570-585, p570, which displayed similar characteristics to p524, was a protective epitope by showing that p570-expanded CD4(+CD25(+ T cells suppressed the onset of diabetes in NOD mice. CONCLUSIONS/SIGNIFICANCE: These data suggest that molecular modeling-based structural analysis of epitopes may be an instrumental tool for prediction of

Biological fundamentals. 2. completely rev. ed

Energy Technology Data Exchange (ETDEWEB)

Sahm, H. (ed.) (Forschungszentrum Juelich GmbH (Germany). Inst. fuer Biotechnologie)

1993-01-01

This fully revised and expanded Second Edition takes into account all recent developments in biotechnology. It is extraordinarily broad in scope, up-to-date, carefully structured and wellbalanced. 'Biotechnology' considers both basic concepts and widely-differing industrial applications: It is a successful synthesis of theory and practice. Any scientist aiming for success in industrial microbiology, biochemistry, molecular biology and chemical engineering must turn to 'Biotechnology'. Everybody involved in biotechnology will appreciate having this volume at their fingertips. It offers a unique collection of current information on the basic biology (ecology, taxonomy, biochemistry, physiology, and genetics) of industrially important organisms. This book contains the background material indispensable for the development of biotechnological processes. Topics included are: - Cell Structure, - Metabolism, - Growth of Microorganisms, - Metabolic Design, - Immobilized Organisms, - Methylotrophs, - Pseudomonas, - Yeasts, - Filamentous Fungi, - Bacteriophages, - Cell Cultures. (orig.)

Preventive Ethics Through Expanding Education.

Science.gov (United States)

Ho, Anita; MacDonald, Lisa Mei-Hwa; Unger, David

2016-03-01

Healthcare institutions have been making increasing efforts to standardize consultation methodology and to accredit both bioethics training programs and the consultants accordingly. The focus has traditionally been on the ethics consultation as the relevant unit of ethics intervention. Outcome measures are studied in relation to consultations, and the hidden assumption is that consultations are the preferred or best way to address day-to-day ethical dilemmas. Reflecting on the data from an internal quality improvement survey and the literature, we argue that having general ethics education as a key function of ethics services may be more important in meeting the contemporaneous needs of acute care settings. An expanded and varied ethics education, with attention to the time constraints of healthcare workers' schedules, was a key recommendation brought forward by survey respondents. Promoting ethical reflection and creating a culture of ethics may serve to prevent ethical dilemmas or mitigate their effects.

Synthesis and Characterization of Rhodamine B-ethylenediamine-hyaluronan Acid as Potential Biological Functional Materials

Science.gov (United States)

Li, Y. L.; Wang, W. X.; Wang, Y.; Zhang, W. B.; Gong, H. M.; Liu, M. X.

2018-05-01

The purpose of this study is to synthesize and characterize fluorescent polymers, rhodamine B-ethylenediamine-hyaluronan acid (RhB-EA-HA). RhB-EA-HA was successfully synthesized by ester ammonolysis reaction and amidation reaction. Moreover, the structural properties of RhB-EA-HA were characterized by 1H-NMR spectra, UV-vis spectrometry and Fourier transform infrared spectroscopy (FT-IR). RhB-EA-HA can be grafted on the surface of silica nanomaterials, which may be potential biological functional materials for drug delivery system.

A Critical Perspective on Synthetic Biology

OpenAIRE

Michel Morange

2009-01-01

Synthetic biology emerged around 2000 as a new biological discipline. It shares with systems biology the same modular vision of organisms, but is more concerned with applications than with a better understanding of the functioning of organisms. A herald of this new discipline is Craig Venter who aims to create an artificial microorganism with the minimal genome compatible with life and to implement into it different 'functional modules' to generate new micro-organisms adapted to specific task...

Computational structural biology: methods and applications

National Research Council Canada - National Science Library

Schwede, Torsten; Peitsch, Manuel Claude

2008-01-01

... sequencing reinforced the observation that structural information is needed to understand the detailed function and mechanism of biological molecules such as enzyme reactions and molecular recognition events. Furthermore, structures are obviously key to the design of molecules with new or improved functions. In this context, computational structural biology...

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

Science.gov (United States)

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

An expanding universe of the non-coding genome in cancer biology.

Science.gov (United States)

Xue, Bin; He, Lin

2014-06-01

Neoplastic transformation is caused by accumulation of genetic and epigenetic alterations that ultimately convert normal cells into tumor cells with uncontrolled proliferation and survival, unlimited replicative potential and invasive growth [Hanahan,D. et al. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646-674]. Although the majority of the cancer studies have focused on the functions of protein-coding genes, emerging evidence has started to reveal the importance of the vast non-coding genome, which constitutes more than 98% of the human genome. A number of non-coding RNAs (ncRNAs) derived from the 'dark matter' of the human genome exhibit cancer-specific differential expression and/or genomic alterations, and it is increasingly clear that ncRNAs, including small ncRNAs and long ncRNAs (lncRNAs), play an important role in cancer development by regulating protein-coding gene expression through diverse mechanisms. In addition to ncRNAs, nearly half of the mammalian genomes consist of transposable elements, particularly retrotransposons. Once depicted as selfish genomic parasites that propagate at the expense of host fitness, retrotransposon elements could also confer regulatory complexity to the host genomes during development and disease. Reactivation of retrotransposons in cancer, while capable of causing insertional mutagenesis and genome rearrangements to promote oncogenesis, could also alter host gene expression networks to favor tumor development. Taken together, the functional significance of non-coding genome in tumorigenesis has been previously underestimated, and diverse transcripts derived from the non-coding genome could act as integral functional components of the oncogene and tumor suppressor network. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Fibronectin and Kupffer cell function in fulminant hepatic failure

International Nuclear Information System (INIS)

Imawari, M.; Hughes, R.D.; Gove, C.D.; Williams, R.

1985-01-01

The relationship between plasma fibronectin, in vitro plasma opsonic activity, which measures the biological activity of fibronectin, and in vivo Kupffer cell function, as assessed by the systemic clearance of microaggregated [ 125 I]albumin, were determined simultaneously in 15 patients with fulminant hepatic failure and 12 normal subjects. Both the plasma fibronectin and plasma opsonic activity were significantly reduced in patients with fulminant hepatic failure, while the systemic clearance of microaggregated albumin was decreased. There was a significant correlation between plasma fibronectin and the plasma opsonic activity on admission, but no correlation could be detected between either parameter and the clearance of microaggregated albumin. A gelatin-derived plasma expander was shown to block the plasma opsonic activity both in vitro and in vivo. The low plasma fibronectin and decreased clearance of microaggregated albumin in fulminant hepatic failure reflect different aspects of the overall impairment of Kupffer cell function

Biological couplings: Classification and characteristic rules

Institute of Scientific and Technical Information of China (English)

无

2009-01-01

The phenomena that biological functions originate from biological coupling are the important biological foundation of multiple bionics and the significant discoveries in the bionic fields. In this paper, the basic concepts related to biological coupling are introduced from the bionic viewpoint. Constitution, classification and characteristic rules of biological coupling are illuminated, the general modes of biological coupling studies are analyzed, and the prospects of multi-coupling bionics are predicted.

Redox Biology in Neurological Function, Dysfunction, and Aging.

Science.gov (United States)

Franco, Rodrigo; Vargas, Marcelo R

2018-04-23

Reduction oxidation (redox) reactions are central to life and when altered, they can promote disease progression. In the brain, redox homeostasis is recognized to be involved in all aspects of central nervous system (CNS) development, function, aging, and disease. Recent studies have uncovered the diverse nature by which redox reactions and homeostasis contribute to brain physiology, and when dysregulated to pathological consequences. Redox reactions go beyond what is commonly described as oxidative stress and involve redox mechanisms linked to signaling and metabolism. In contrast to the nonspecific nature of oxidative damage, redox signaling involves specific oxidation/reduction reactions that regulate a myriad of neurological processes such as neurotransmission, homeostasis, and degeneration. This Forum is focused on the role of redox metabolism and signaling in the brain. Six review articles from leading scientists in the field that appraise the role of redox metabolism and signaling in different aspects of brain biology including neurodevelopment, neurotransmission, aging, neuroinflammation, neurodegeneration, and neurotoxicity are included. An original research article exemplifying these concepts uncovers a novel link between oxidative modifications, redox signaling, and neurodegeneration. This Forum highlights the recent advances in the field and we hope it encourages future research aimed to understand the mechanisms by which redox metabolism and signaling regulate CNS physiology and pathophysiology. Antioxid. Redox Signal. 00, 000-000.

Gravitational wave memory in an expanding universe

Science.gov (United States)

Tolish, Alexander; Wald, Robert

2016-03-01

We investigate the gravitational wave memory effect in an expanding FLRW spacetime. We find that if the gravitational field is decomposed into gauge-invariant scalar, vector, and tensor modes after the fashion of Bardeen, only the tensor mode gives rise to memory, and this memory can be calculated using the retarded Green's function associated with the tensor wave equation. If locally similar radiation source events occur on flat and FLRW backgrounds, we find that the resulting memories will differ only by a redshift factor, and we explore whether or not this factor depends on the expansion history of the FLRW universe. We compare our results to related work by Bieri, Garfinkle, and Yau.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

Science.gov (United States)

Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

2012-12-15

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

Thermodynamic Analysis on of Skid-Mounted Coal-bed Methane Liquefaction Device using Cryogenic Turbo-Expander

Science.gov (United States)

Chen, Shuangtao; Niu, Lu; Zeng, Qiang; Li, Xiaojiang; Lou, Fang; Chen, Liang; Hou, Yu

2017-12-01

Coal-bed methane (CBM) reserves are rich in Sinkiang of China, and liquefaction is a critical step for the CBM exploration and utilization. Different from other CBM gas fields in China, CBM distribution in Sinkiang is widespread but scattered, and the pressure, flow-rate and nitrogen content of CBM feed vary significantly. The skid-mounted liquefaction device is suggested as an efficient and economical way to recover methane. Turbo-expander is one of the most important parts which generates the cooling capacity for the cryogenic liquefaction system. Using turbo-expander, more cooling capacity and higher liquefied fraction can be achieved. In this study, skid-mounted CBM liquefaction processes based on Claude cycle are established. Cryogenic turbo-expander with high expansion ratio is employed to improve the efficiency of CBM liquefaction process. The unit power consumption per liquefaction mole flow-rate for CBM feed gas is used as the object function for process optimization, compressor discharge pressure, flow ratio of feed gas to turbo-expander and nitrogen friction are analyzed, and optimum operation range of the liquefaction processes are obtained.

Minimalistic peptide supramolecular co-assembly: expanding the conformational space for nanotechnology.

Science.gov (United States)

Makam, Pandeeswar; Gazit, Ehud

2018-05-21

Molecular self-assembly is a ubiquitous process in nature and central to bottom-up nanotechnology. In particular, the organization of peptide building blocks into ordered supramolecular structures has gained much interest due to the unique properties of the products, including biocompatibility, chemical and structural diversity, robustness and ease of large-scale synthesis. In addition, peptides, as short as dipeptides, contain all the molecular information needed to spontaneously form well-ordered structures at both the nano- and the micro-scale. Therefore, peptide supramolecular assembly has been effectively utilized to produce novel materials with tailored properties for various applications in the fields of material science, engineering, medicine, and biology. To further expand the conformational space of peptide assemblies in terms of structural and functional complexity, multicomponent (two or more) peptide supramolecular co-assembly has recently evolved as a promising extended approach, similar to the structural diversity of natural sequence-defined biopolymers (proteins) as well as of synthetic covalent co-polymers. The use of this methodology was recently demonstrated in various applications, such as nanostructure physical dimension control, the creation of non-canonical complex topologies, mechanical strength modulation, the design of light harvesting soft materials, fabrication of electrically conducting devices, induced fluorescence, enzymatic catalysis and tissue engineering. In light of these significant advancements in the field of peptide supramolecular co-assembly in the last few years, in this tutorial review, we provide an updated overview and future prospects of this emerging subject.

Expand your English a guide to improving your academic vocabulary

CERN Document Server

Hart, Steve

2018-01-01

Writing academic prose in English is especially difficult for non-native speakers, largely because the standard vocabulary used in this genre can be quite different from colloquial English. Expand Your English: A Guide to Improving Your Academic Vocabulary is a unique and invaluable guide that will enable the reader to overcome this hurdle. It will become the favourite go-to reference book for both beginners and for intermediate learners struggling with the complexities of English-language academic writing. Steve Hart covers 1,000 vocabulary items that are essential for good academic writing. The first section describes 200 key terms in detail, grouping them into logical sets of 10. Through careful repetition, the reader will find it easy to retain, retrieve, and reuse these essential phrases. The second section explains a further 800 terms, grouping them according to function, meaning, and the areas of an essay where they are likely to be used. The expansive scope of Expand Your English gives non-native spea...

Accurate Estimation of Target amounts Using Expanded BASS Model for Demand-Side Management

Science.gov (United States)

Kim, Hyun-Woong; Park, Jong-Jin; Kim, Jin-O.

2008-10-01

The electricity demand in Korea has rapidly increased along with a steady economic growth since 1970s. Therefore Korea has positively propelled not only SSM (Supply-Side Management) but also DSM (Demand-Side Management) activities to reduce investment cost of generating units and to save supply costs of electricity through the enhancement of whole national energy utilization efficiency. However study for rebate, which have influence on success or failure on DSM program, is not sufficient. This paper executed to modeling mathematically expanded Bass model considering rebates, which have influence on penetration amounts for DSM program. To reflect rebate effect more preciously, the pricing function using in expanded Bass model directly reflects response of potential participants for rebate level.

A preliminary approach to creating an overview of lactoferrin multi-functionality utilizing a text mining method.

Science.gov (United States)

Shimazaki, Kei-ichi; Kushida, Tatsuya

2010-06-01

Lactoferrin is a multi-functional metal-binding glycoprotein that exhibits many biological functions of interest to many researchers from the fields of clinical medicine, dentistry, pharmacology, veterinary medicine, nutrition and milk science. To date, a number of academic reports concerning the biological activities of lactoferrin have been published and are easily accessible through public data repositories. However, as the literature is expanding daily, this presents challenges in understanding the larger picture of lactoferrin function and mechanisms. In order to overcome the "analysis paralysis" associated with lactoferrin information, we attempted to apply a text mining method to the accumulated lactoferrin literature. To this end, we used the information extraction system GENPAC (provided by Nalapro Technologies Inc., Tokyo). This information extraction system uses natural language processing and text mining technology. This system analyzes the sentences and titles from abstracts stored in the PubMed database, and can automatically extract binary relations that consist of interactions between genes/proteins, chemicals and diseases/functions. We expect that such information visualization analysis will be useful in determining novel relationships among a multitude of lactoferrin functions and mechanisms. We have demonstrated the utilization of this method to find pathways of lactoferrin participation in neovascularization, Helicobacter pylori attack on gastric mucosa, atopic dermatitis and lipid metabolism.

Integration of multiscale dendritic spine structure and function data into systems biology models

Directory of Open Access Journals (Sweden)

James J Mancuso

2014-11-01

Full Text Available Comprising 1011 neurons with 1014 synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the massive big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement.

New generation expandable sand screens

OpenAIRE

Syltøy, Christer

2014-01-01

Master's thesis in Petroleum engineering This thesis aims to give a general insight into sand control and various sorts of sand control measures and applications of sand control tools. Special focus will be given to expandable sand screens – a technology which came about in the late 1990’s through the use of flexible, expandable tubulars as base pipe in sand screens. More specifically Darcy’s Hydraulic Endurance Screens, a compliant sand screen system using hydraulic activation, and the fu...

IMP 2.0: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks.

Science.gov (United States)

Wong, Aaron K; Krishnan, Arjun; Yao, Victoria; Tadych, Alicja; Troyanskaya, Olga G

2015-07-01

IMP (Integrative Multi-species Prediction), originally released in 2012, is an interactive web server that enables molecular biologists to interpret experimental results and to generate hypotheses in the context of a large cross-organism compendium of functional predictions and networks. The system provides biologists with a framework to analyze their candidate gene sets in the context of functional networks, expanding or refining their sets using functional relationships predicted from integrated high-throughput data. IMP 2.0 integrates updated prior knowledge and data collections from the last three years in the seven supported organisms (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Caenorhabditis elegans, and Saccharomyces cerevisiae) and extends function prediction coverage to include human disease. IMP identifies homologs with conserved functional roles for disease knowledge transfer, allowing biologists to analyze disease contexts and predictions across all organisms. Additionally, IMP 2.0 implements a new flexible platform for experts to generate custom hypotheses about biological processes or diseases, making sophisticated data-driven methods easily accessible to researchers. IMP does not require any registration or installation and is freely available for use at http://imp.princeton.edu. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Detection of Metabolism Function of Microbial Community of Corpses by Biolog-Eco Method.

Science.gov (United States)

Jiang, X Y; Wang, J F; Zhu, G H; Ma, M Y; Lai, Y; Zhou, H

2016-06-01

To detect the changes of microbial community functional diversity of corpses with different postmortem interval （PMI） and to evaluate forensic application value for estimating PMI. The cultivation of microbial community from the anal swabs of a Sus scrofa and a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Microplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial community on the decomposed corpse under natural environment were also observed. The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples became relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components （accumulative contribution ratio >90%）.The carbon source tsquare-analysis showed that N -acetyl- D -glucosamine and L -serine were the dominant carbon sources for estimating the PMI （0=240 h） of the Sus scrofa and human corpse. The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI. Copyright© by the Editorial Department of Journal of Forensic Medicine

Review of Biological Network Data and Its Applications

Directory of Open Access Journals (Sweden)

Donghyeon Yu

2013-12-01

Full Text Available Studying biological networks, such as protein-protein interactions, is key to understanding complex biological activities. Various types of large-scale biological datasets have been collected and analyzed with high-throughput technologies, including DNA microarray, next-generation sequencing, and the two-hybrid screening system, for this purpose. In this review, we focus on network-based approaches that help in understanding biological systems and identifying biological functions. Accordingly, this paper covers two major topics in network biology: reconstruction of gene regulatory networks and network-based applications, including protein function prediction, disease gene prioritization, and network-based genome-wide association study.

Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

Science.gov (United States)

Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

2015-08-01

Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

Science.gov (United States)

Sukhikh, E.; Sheino, I.; Vertinsky, A.

2017-09-01

Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

Encapsulation of gold nanoparticles into self-assembling protein nanoparticles

OpenAIRE

Yang Yongkun; Burkhard Peter

2012-01-01

Abstract Background Gold nanoparticles are useful tools for biological applications due to their attractive physical and chemical properties. Their applications can be further expanded when they are functionalized with biological molecules. The biological molecules not only provide the interfaces for interactions between nanoparticles and biological environment, but also contribute their biological functions to the nanoparticles. Therefore, we used self-assembling protein nanoparticles (SAPNs...

Scaffolded biology.

Science.gov (United States)

Minelli, Alessandro

2016-09-01

Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

Invariant graphs of a family of non-uniformly expanding skew products over Markov maps

Science.gov (United States)

Walkden, C. P.; Withers, T.

2018-06-01

We consider a family of skew-products of the form where T is a continuous, expanding, locally eventually onto Markov map and is a family of homeomorphisms of . A function is said to be an invariant graph if is an invariant set for the skew-product; equivalently, u(T(x))  =  g x (u(x)). A well-studied problem is to consider the existence, regularity and dimension-theoretic properties of such functions, usually under strong contraction or expansion conditions (in terms of Lyapunov exponents or partial hyperbolicity) in the fibre direction. Here we consider such problems in a setting where the Lyapunov exponent in the fibre direction is zero on a set of periodic orbits but expands except on a neighbourhood of these periodic orbits. We prove that u either has the structure of a ‘quasi-graph’ (or ‘bony graph’) or is as smooth as the dynamics, and we give a criteria for this to happen.

Partition expanders

Czech Academy of Sciences Publication Activity Database

Gavinsky, Dmitry; Pudlák, Pavel

2017-01-01

Roč. 60, č. 3 (2017), s. 378-395 ISSN 1432-4350 R&D Projects: GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : expanders * pseudorandomness * communication complexity Subject RIV: BA - General Mathematics OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.645, year: 2016 http://link.springer.com/article/10.1007%2Fs00224-016-9738-5

Exploring new biological functions of amyloids: bacteria cell agglutination mediated by host protein aggregation.

Directory of Open Access Journals (Sweden)

Marc Torrent

Full Text Available Antimicrobial proteins and peptides (AMPs are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance.

Arms Control: US and International efforts to ban biological weapons

Energy Technology Data Exchange (ETDEWEB)

1992-12-01

The Bacteriological (Biological) and Toxin Weapons Convention, the treaty that bans the development, production, and stockpiling and acquisition of biological weapons was opened for signature in 1972 and came into force in 1975 after being ratified by 22 governments, including the depository nations of the USA, the United Kingdom, and the former Soviet Union. In support of the Convention, the USA later established export controls on items used to make biological weapons. Further, in accordance with the 1990 President`s Enhanced Proliferation Control Initiative, actions were taken to redefine and expand US export controls, as well as to encourage multilateral controls through the Australia Group. Thus far, the Convention has not been effective in stopping the development of biological weapons. The principal findings as to the reasons of the failures of the Convention are found to be: the Convention lacks universality, compliance measures are effective, advantage of verification may outweigh disadvantages. Recommendations for mitigating these failures are outlined in this report.

The triad value function

DEFF Research Database (Denmark)

Vedel, Mette

2016-01-01

the triad value function. Next, the applicability and validity of the concept is examined in a case study of four closed vertical supply chain triads. Findings - The case study demonstrates that the triad value function facilitates the analysis and understanding of an apparent paradox; that distributors...... are not dis-intermediated in spite of their limited contribution to activities in the triads. The results indicate practical adequacy of the triad value function. Research limitations/implications - The triad value function is difficult to apply in the study of expanded networks as the number of connections...... expands exponentially with the number of ties in the network. Moreover, it must be applied in the study of service triads and open vertical supply chain triads to further verify the practical adequacy of the concept. Practical implications - The triad value function cannot be used normatively...

Multifunctional and biologically active matrices from multicomponent polymeric solutions

Science.gov (United States)

Kiick, Kristi L. (Inventor); Yamaguchi, Nori (Inventor)

2010-01-01

The present invention relates to a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of biologically active agents. In particular the invention relates to a functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin. Examples of active molecules that may be used with the multicomponent polymer of the invention include, for example, a drug, a biopolymer, for example a growth factor, a protein, a peptide, a nucleotide, a polysaccharide, a biological macromolecule or the like. The invention is further directed to the formation of functionalized crosslinked matrices, such as hydrogels, that include at least one functionalized compatibilizing polymer capable of assembly.

Efficient farnesylation of an extended C-terminal C(x)3X sequence motif expands the scope of the prenylated proteome.

Science.gov (United States)

Blanden, Melanie J; Suazo, Kiall F; Hildebrandt, Emily R; Hardgrove, Daniel S; Patel, Meet; Saunders, William P; Distefano, Mark D; Schmidt, Walter K; Hougland, James L

2018-02-23

Protein prenylation is a post-translational modification that has been most commonly associated with enabling protein trafficking to and interaction with cellular membranes. In this process, an isoprenoid group is attached to a cysteine near the C terminus of a substrate protein by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I or II (GGTase-I and GGTase-II). FTase and GGTase-I have long been proposed to specifically recognize a four-amino acid C AAX C-terminal sequence within their substrates. Surprisingly, genetic screening reveals that yeast FTase can modify sequences longer than the canonical C AAX sequence, specifically C( x ) 3 X sequences with four amino acids downstream of the cysteine. Biochemical and cell-based studies using both peptide and protein substrates reveal that mammalian FTase orthologs can also prenylate C( x ) 3 X sequences. As the search to identify physiologically relevant C( x ) 3 X proteins begins, this new prenylation motif nearly doubles the number of proteins within the yeast and human proteomes that can be explored as potential FTase substrates. This work expands our understanding of prenylation's impact within the proteome, establishes the biologically relevant reactivity possible with this new motif, and opens new frontiers in determining the impact of non-canonically prenylated proteins on cell function. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Towards biologically conformal radiation therapy (BCRT): Selective IMRT dose escalation under the guidance of spatial biology distribution

International Nuclear Information System (INIS)

Yang Yong; Xing Lei

2005-01-01

It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT

Flow boiling in expanding microchannels

CERN Document Server

Alam, Tamanna

2017-01-01

This Brief presents an up to date summary of details of the flow boiling heat transfer, pressure drop and instability characteristics; two phase flow patterns of expanding microchannels. Results obtained from the different expanding microscale geometries are presented for comparison and addition to that, comparison with literatures is also performed. Finally, parametric studies are performed and presented in the brief. The findings from this study could help in understanding the complex microscale flow boiling behavior and aid in the design and implementation of reliable compact heat sinks for practical applications.

Biofabrication to build the biology-device interface

International Nuclear Information System (INIS)

Liu Yi; Kim, Eunkyoung; Culver, James N; Bentley, William E; Payne, Gregory F; Ghodssi, Reza; Rubloff, Gary W

2010-01-01

The last century witnessed spectacular advances in both microelectronics and biotechnology yet there was little synergy between the two. A challenge to their integration is that biological and electronic systems are constructed using divergent fabrication paradigms. Biology fabricates bottom-up with labile components, while microelectronic devices are fabricated top-down using methods that are 'bio-incompatible'. Biofabrication-the use of biological materials and mechanisms for construction-offers the opportunity to span these fabrication paradigms by providing convergent approaches for building the bio-device interface. Integral to biofabrication are stimuli-responsive materials (e.g. film-forming polysaccharides) that allow directed assembly under near physiological conditions in response to device-imposed signals. Biomolecular engineering, through recombinant technology, allows biological components to be endowed with information for assembly (e.g. encoded in a protein's amino acid sequence). Finally, self-assembly and enzymatic assembly provide the mechanisms for construction over a hierarchy of length scales. Here, we review recent advances in the use of biofabrication to build the bio-device interface. We anticipate that the biofabrication toolbox will expand over the next decade as more researchers enlist the unique construction capabilities of biology. Further, we look forward to observing the application of this toolbox to create devices that can better diagnose disease, detect pathogens and discover drugs. Finally, we expect that biofabrication will enable the effective interfacing of biology with electronics to create implantable devices for personalized and regenerative medicine. (topical review)

Using Technology to Expand the Classroom in Time, Space, and Diversity.

Science.gov (United States)

Drew, Joshua

2015-11-01

Diverse classrooms offer distinct advantages over homogeneous classrooms, for example by providing a greater diversity of perspectives and opportunities. However, there is substantial underrepresentation of numerous groups throughout science, technology, engineering, and mathematics (STEM) education, from secondary schools through professional ranks and academia. In this piece I offer a critical analysis of three worked examples of how technology can be used to expand traditional definitions of the classroom environment. In doing so I show how technology can be used to help make STEM classrooms more expansive, equitable, and effective learning environments. First I highlight how peer-to-peer learning was used to foster knowledge of marine conservation with high school youth across Fiji and Chicago. Second I show how social media can be used to facilitate conversations in New York City after a natural disaster. Finally, I show how integrating digital and real-world learning can help a diverse group of students from the Pacific islands gain field-based STEM techniques in an extended workshop format. Taken together these examples show how digital technology could expand the fixed walls of the academy and that technology can help show students the vivid splendor of life outside the classroom. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Genome-wide association study and biological pathway analysis of the Eimeria maxima response in broilers.

Science.gov (United States)

Hamzić, Edin; Buitenhuis, Bart; Hérault, Frédéric; Hawken, Rachel; Abrahamsen, Mitchel S; Servin, Bertrand; Elsen, Jean-Michel; Pinard-van der Laan, Marie-Hélène; Bed'Hom, Bertrand

2015-11-25

Coccidiosis is the most common and costly disease in the poultry industry and is caused by protozoans of the Eimeria genus. The current control of coccidiosis, based on the use of anticoccidial drugs and vaccination, faces serious obstacles such as drug resistance and the high costs for the development of efficient vaccines, respectively. Therefore, the current control programs must be expanded with complementary approaches such as the use of genetics to improve the host response to Eimeria infections. Recently, we have performed a large-scale challenge study on Cobb500 broilers using E. maxima for which we investigated variability among animals in response to the challenge. As a follow-up to this challenge study, we performed a genome-wide association study (GWAS) to identify genomic regions underlying variability of the measured traits in the response to Eimeria maxima in broilers. Furthermore, we conducted a post-GWAS functional analysis to increase our biological understanding of the underlying response to Eimeria maxima challenge. In total, we identified 22 single nucleotide polymorphisms (SNPs) with q value Eimeria maxima in broilers. Furthermore, the post-GWAS functional analysis indicates that biological pathways and networks involved in tissue proliferation and repair along with the primary innate immune response may play the most important role during the early stage of Eimeria maxima infection in broilers.

Understanding Biological Regulation Through Synthetic Biology.

Science.gov (United States)

Bashor, Caleb J; Collins, James J

2018-03-16

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The changing world of modern cell biology.

Science.gov (United States)

Misteli, Tom

2009-01-12

Change is always ambiguous. There is the enticing prospect of novelty and better times ahead, but at the same time the concern of losing the good of the past. It is with these sentiments that I take over as the Editor-in-Chief from Ira Mellman who for a decade has cleverly and effectively lead the JCB. During this time he directed and oversaw an extensive modernization of the journal and guided it through dramatic changes in the publishing world. Ira lead the journal with unyielding dedication and enthusiasm and we in the cell biology community must thank him profoundly for his service. It is his work, together with the invaluable contribution of the best editorial board and the most dedicated professional editorial staff in the scientific publishing business, that allows me to now take over the stewardship of the JCB with a tremendous sense of excitement and determination to continue and expand the JCB's role as the leading journal in the cell biology community and as a trendsetter in the rapidly changing world of modern cell biology.

Systems Biology of Industrial Microorganisms

Science.gov (United States)

Papini, Marta; Salazar, Margarita; Nielsen, Jens

The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

Usefulness and limitations of dK random graph models to predict interactions and functional homogeneity in biological networks under a pseudo-likelihood parameter estimation approach

Directory of Open Access Journals (Sweden)

Luan Yihui

2009-09-01

Full Text Available Abstract Background Many aspects of biological functions can be modeled by biological networks, such as protein interaction networks, metabolic networks, and gene coexpression networks. Studying the statistical properties of these networks in turn allows us to infer biological function. Complex statistical network models can potentially more accurately describe the networks, but it is not clear whether such complex models are better suited to find biologically meaningful subnetworks. Results Recent studies have shown that the degree distribution of the nodes is not an adequate statistic in many molecular networks. We sought to extend this statistic with 2nd and 3rd order degree correlations and developed a pseudo-likelihood approach to estimate the parameters. The approach was used to analyze the MIPS and BIOGRID yeast protein interaction networks, and two yeast coexpression networks. We showed that 2nd order degree correlation information gave better predictions of gene interactions in both protein interaction and gene coexpression networks. However, in the biologically important task of predicting functionally homogeneous modules, degree correlation information performs marginally better in the case of the MIPS and BIOGRID protein interaction networks, but worse in the case of gene coexpression networks. Conclusion Our use of dK models showed that incorporation of degree correlations could increase predictive power in some contexts, albeit sometimes marginally, but, in all contexts, the use of third-order degree correlations decreased accuracy. However, it is possible that other parameter estimation methods, such as maximum likelihood, will show the usefulness of incorporating 2nd and 3rd degree correlations in predicting functionally homogeneous modules.

Usefulness and limitations of dK random graph models to predict interactions and functional homogeneity in biological networks under a pseudo-likelihood parameter estimation approach.

Science.gov (United States)

Wang, Wenhui; Nunez-Iglesias, Juan; Luan, Yihui; Sun, Fengzhu

2009-09-03

Many aspects of biological functions can be modeled by biological networks, such as protein interaction networks, metabolic networks, and gene coexpression networks. Studying the statistical properties of these networks in turn allows us to infer biological function. Complex statistical network models can potentially more accurately describe the networks, but it is not clear whether such complex models are better suited to find biologically meaningful subnetworks. Recent studies have shown that the degree distribution of the nodes is not an adequate statistic in many molecular networks. We sought to extend this statistic with 2nd and 3rd order degree correlations and developed a pseudo-likelihood approach to estimate the parameters. The approach was used to analyze the MIPS and BIOGRID yeast protein interaction networks, and two yeast coexpression networks. We showed that 2nd order degree correlation information gave better predictions of gene interactions in both protein interaction and gene coexpression networks. However, in the biologically important task of predicting functionally homogeneous modules, degree correlation information performs marginally better in the case of the MIPS and BIOGRID protein interaction networks, but worse in the case of gene coexpression networks. Our use of dK models showed that incorporation of degree correlations could increase predictive power in some contexts, albeit sometimes marginally, but, in all contexts, the use of third-order degree correlations decreased accuracy. However, it is possible that other parameter estimation methods, such as maximum likelihood, will show the usefulness of incorporating 2nd and 3rd degree correlations in predicting functionally homogeneous modules.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

Science.gov (United States)

Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

2015-01-01

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

The expanding universe of p53 targets.

Science.gov (United States)

Menendez, Daniel; Inga, Alberto; Resnick, Michael A

2009-10-01

The p53 tumour suppressor is modified through mutation or changes in expression in most cancers, leading to the altered regulation of hundreds of genes that are directly influenced by this sequence-specific transcription factor. Central to the p53 master regulatory network are the target response element (RE) sequences. The extent of p53 transactivation and transcriptional repression is influenced by many factors, including p53 levels, cofactors and the specific RE sequences, all of which contribute to the role that p53 has in the aetiology of cancer. This Review describes the identification and functionality of REs and highlights the inclusion of non-canonical REs that expand the universe of genes and regulation mechanisms in the p53 tumour suppressor network.

[Historic and functional biology: the inadequacy of a system theory of evolution].

Science.gov (United States)

Regelmann, J P

1982-01-01

In the first half of the 20th century neo-Kantianism in a broad sense proved itself the main conceptual and methodological background of the central European biology. As such it contributed much to the victory on the typological, idealistic-morphological and psycho-vitalistic interpretations of life. On the other hand it could not give tools to the biologists for working out a strictly darwinian evolution theory. Kant's theory of organism was conceived without evolution as a theory of the internal functionality of the organism. There was only some 'play' with the evolutionary differentiation of the species. Since then the disputes around the work of August Weismann, a synthetical evolution theory which is now behind time, arose. This theory developed from coinciding claims, elaborated by geneticists, mathematicians, and by biologists studying development, natural history and systematics. This was done under a strong influence of marxist ideas. Through the interweaving of such different approaches it was possible for this evolutionary synthesis to influence successfully the development of evolution research during more than 40 years. Philosophically speaking modern evolution theory means therefore an aversion, even a positive abolition of Kantian positions. A number of biologists however--as L. von Bertalanffy--refused to adhere to a misinterpreted Kantian methodology and oriented themselves to an approach via system theory, which obtained a place in evolution research. In fact this is a Kantian approach as well. They only repeated the Kantian dilemma of the evolution which can also be found in Lamarck and Hegel. The system theory of the functionality of the organism never reaches to the level of the evolving species, but remains always on the level of epigenetic thinking, because of its philosophical origin. This paper points out the consequences of this still current dilemma. At the same time an all-enclosing reflection on the methodological, epistemological and

Entropy in an expanding universe

International Nuclear Information System (INIS)

Frautschi, S.

1982-01-01

The question of how the observed evolution of organized structures from initial chaos in the expanding universe can be reconciled with the laws of statistical mechanics is studied, with emphasis on effects of the expansion and gravity. Some major sources of entropy increase are listed. An expanding causal region is defined in which the entropy, though increasing, tends to fall further and further behind its maximum possible value, thus allowing for the development of order. The related questions of whether entropy will continue increasing without limit in the future, and whether such increase in the form of Hawking radiation or radiation from positronium might enable life to maintain itself permanently, are considered. Attempts to find a scheme for preserving life based on solid structures fail because events such as quantum tunneling recurrently disorganize matter on a very long but fixed time scale, whereas all energy sources slow down progressively in an expanding universe. However, there remains hope that other modes of life capable of maintaining themselves permanently can be found

The JCSG high-throughput structural biology pipeline

International Nuclear Information System (INIS)

Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wooley, John; Wüthrich, Kurt; Wilson, Ian A.

2010-01-01

The Joint Center for Structural Genomics high-throughput structural biology pipeline has delivered more than 1000 structures to the community over the past ten years and has made a significant contribution to the overall goal of the NIH Protein Structure Initiative (PSI) of expanding structural coverage of the protein universe. The Joint Center for Structural Genomics high-throughput structural biology pipeline has delivered more than 1000 structures to the community over the past ten years. The JCSG has made a significant contribution to the overall goal of the NIH Protein Structure Initiative (PSI) of expanding structural coverage of the protein universe, as well as making substantial inroads into structural coverage of an entire organism. Targets are processed through an extensive combination of bioinformatics and biophysical analyses to efficiently characterize and optimize each target prior to selection for structure determination. The pipeline uses parallel processing methods at almost every step in the process and can adapt to a wide range of protein targets from bacterial to human. The construction, expansion and optimization of the JCSG gene-to-structure pipeline over the years have resulted in many technological and methodological advances and developments. The vast number of targets and the enormous amounts of associated data processed through the multiple stages of the experimental pipeline required the development of variety of valuable resources that, wherever feasible, have been converted to free-access web-based tools and applications

Synthetic Biology Tools for the Membrane – Targeted Localisation and Elucidation of Protein Interactions

DEFF Research Database (Denmark)

Wendel, Sofie; Seppala, Susanna; Nørholm, Morten

2014-01-01

To meet the need for new, green production scenarios, development of biological cell factories is becoming increasingly important. In order for cell factories to compete with traditional production means, it is essential to expand the available toolbox. We are developing tools for the E. coli cel...

Evidence of pervasive biologically functional secondary structures within the genomes of eukaryotic single-stranded DNA viruses.

Science.gov (United States)

Muhire, Brejnev Muhizi; Golden, Michael; Murrell, Ben; Lefeuvre, Pierre; Lett, Jean-Michel; Gray, Alistair; Poon, Art Y F; Ngandu, Nobubelo Kwanele; Semegni, Yves; Tanov, Emil Pavlov; Monjane, Adérito Luis; Harkins, Gordon William; Varsani, Arvind; Shepherd, Dionne Natalie; Martin, Darren Patrick

2014-02-01

Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here.

Solid expandable systems put deepwater targets within reach

Energy Technology Data Exchange (ETDEWEB)

Perez-Roca, Eduardo [Enventure Global Technology L.L.C., Houston, TX (United States). Latin America; Fristch, Jerry [Enventure Global Technology L.L.C., Houston, TX (United States)

2008-07-01

Enabling technologies that take drilling operations to deeper objectives have made a significant impact on the practicality of many projects, especially deep water offshore targets. Increasing vertical depth and lateral reach requires adequate hole size to attain the desired objectives of the well bore. Solid expandable technology can maintain and retain hole size to address both the physical limitations and the economic feasibility of deep water operations. With each and every casing point, the potential for adequate hole size at total depth (TD) decreases. Solid expandable open hole liners and single-diameter systems reduce and eliminate, respectively, the well bore tapering that dictates hole size at TD and subsequent completion size. Successful mitigation of this tapering, whether through the entire well bore or through select zones, enables operators to gain access to previously unreachable reserves. Solid expandable systems have proven to be reliable and effective with over 1,000 installations in a myriad of conditions and environments worldwide. To date, over 115 of those applications have been in deep water environments. The current operating envelope for solid expandable systems include the deepest installation at {approx}28,750 ft (8,763 m) and the longest at 6,867 ft (2,083 m) in water depth over 3,150 ft (960 m). This record-length application consisted of an open hole liner installed and expanded in a single run. This paper will discuss the effectiveness of solid expandable systems in deep water operations and how the technology brings value to offshore projects especially when planned into the initial design. Case histories will be used to further illustrate the features, advantages, and benefits of expandable technology. In addition, this paper will examine the state of the solid expandable technology and its continuing evolution to provide even more drilling solutions. (author)

Editorial overview : Systems biology for biotechnology

NARCIS (Netherlands)

Heinemann, Matthias; Pilpel, Yitzhak

About 15 years ago, systems biology was introduced as a novel approach to biological research. On the one side, its introduction was a result of the recognition that through solely the reductionist approach, we would ulti- mately not be able to understand how biological systems function as a whole.

e-Biologics: Fabrication of Sustainable Electronics with "Green" Biological Materials.

Science.gov (United States)

Lovley, Derek R

2017-06-27

The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial components as the guide for synthesis, are a potential green solution. Some e-biologics can be fabricated from renewable feedstocks with relatively low energy inputs, often while avoiding the harsh chemicals used for synthesizing more traditional electronic materials. Several are completely free of toxic components, can be readily recycled, and offer unique features not found in traditional electronic materials in terms of size, performance, and opportunities for diverse functionalization. An appropriate investment in the concerted multidisciplinary collaborative research required to identify and characterize e-biologics and to engineer materials and devices based on e-biologics could be rewarded with a new "green age" of sustainable electronic materials and devices. Copyright © 2017 Lovley.

The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.

Science.gov (United States)

Tochowicz, Anna; Goettig, Peter; Evans, Richard; Visse, Robert; Shitomi, Yasuyuki; Palmisano, Ralf; Ito, Noriko; Richter, Klaus; Maskos, Klaus; Franke, Daniel; Svergun, Dmitri; Nagase, Hideaki; Bode, Wolfram; Itoh, Yoshifumi

2011-03-04

Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 Å resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.

Ab Initio Calculations of the Electronic Structures and Biological Functions of Protein Molecules

Science.gov (United States)

Zheng, Haoping

2003-04-01

The self-consistent cluster-embedding (SCCE) calculation method reduces the computational effort from M3 to about M1 (M is the number of atoms in the system) with unchanged calculation precision. So the ab initio, all-electron calculation of the electronic structure and biological function of protein molecule becomes a reality, which will promote new proteomics considerably. The calculated results of two real protein molecules, the trypsin inhibitor from the seeds of squash Cucurbita maxima (CMTI-I, 436 atoms) and the Ascaris trypsin inhibitor (912 atoms, two three-dimensional structures), are presented. The reactive sites of the inhibitors are determined and explained. The precision of structure determination of inhibitors are tested theoretically.

Nanobodies and recombinant binders in cell biology.

Science.gov (United States)

Helma, Jonas; Cardoso, M Cristina; Muyldermans, Serge; Leonhardt, Heinrich

2015-06-08

Antibodies are key reagents to investigate cellular processes. The development of recombinant antibodies and binders derived from natural protein scaffolds has expanded traditional applications, such as immunofluorescence, binding arrays, and immunoprecipitation. In addition, their small size and high stability in ectopic environments have enabled their use in all areas of cell research, including structural biology, advanced microscopy, and intracellular expression. Understanding these novel reagents as genetic modules that can be integrated into cellular pathways opens up a broad experimental spectrum to monitor and manipulate cellular processes. © 2015 Helma et al.

Nanobodies and recombinant binders in cell biology

Science.gov (United States)

Helma, Jonas; Cardoso, M. Cristina; Muyldermans, Serge

2015-01-01

Antibodies are key reagents to investigate cellular processes. The development of recombinant antibodies and binders derived from natural protein scaffolds has expanded traditional applications, such as immunofluorescence, binding arrays, and immunoprecipitation. In addition, their small size and high stability in ectopic environments have enabled their use in all areas of cell research, including structural biology, advanced microscopy, and intracellular expression. Understanding these novel reagents as genetic modules that can be integrated into cellular pathways opens up a broad experimental spectrum to monitor and manipulate cellular processes. PMID:26056137

Phytochrome from Green Plants: Properties and biological Function

Energy Technology Data Exchange (ETDEWEB)

Quail, Peter H.

2014-07-25

Pfr conformer reverses this activity upon initial light exposure, inducing the switch to photomorphogenic development. This reversal involves light-triggered translocation of the photoactivated phy molecule into the nucleus where it interacts with PIF-family members, inducing rapid phosphorylation and degradation of the PIFs via the ubiquitin-proteasome system. This degradation in turn elicits rapid alterations in gene expression that drive the deetiolation transition. This project has made considerable progress in defining phy-PIF signaling activity in controlling the SAR. The biological functions of the multiple PIF-family members in controlling the SAR, including dissection of the relative contributions of the individual PIFs to this process, as well as to diurnal growth-control oscillations, have been investigated using higher-order pif-mutant combinations. Using microarray analysis of a quadruple pif mutant we have defined the shade-induced, PIF-regulated transcriptional network genome-wide. This has revealed that a dynamic antagonism between the phys and PIFs generates selective reciprocal responses during deetiolation and the SAR in a rapidly light-responsive transcriptional network. Using integrated RNA-seq and ChIP-seq analysis of higher order pif-mutant combinations, we have defined the direct gene-targets of PIF transcriptional regulation, and have obtained evidence that this regulation involves differential direct targeting of rapidly light-responsive genes by the individual PIF-family members. This project has provided significant advances in our understanding of the molecular mechanisms by which the phy-PIF photosensory signaling pathway regulates an important bioenergy-related plant response to the light environment. The identification of molecular targets in the primary transcriptional-regulatory circuitry of this pathway has the potential to enable genetic or reverse-genetic manipulation of the partitioning of carbon between reproductive and

Membrane mimetic surface functionalization of nanoparticles: Methods and applications

Science.gov (United States)

Weingart, Jacob; Vabbilisetty, Pratima; Sun, Xue-Long

2013-01-01

Nanoparticles (NPs), due to their size-dependent physical and chemical properties, have shown remarkable potential for a wide range of applications over the past decades. Particularly, the biological compatibilities and functions of NPs have been extensively studied for expanding their potential in areas of biomedical application such as bioimaging, biosensing, and drug delivery. In doing so, surface functionalization of NPs by introducing synthetic ligands and/or natural biomolecules has become a critical component in regards to the overall performance of the NP system for its intended use. Among known examples of surface functionalization, the construction of an artificial cell membrane structure, based on phospholipids, has proven effective in enhancing biocompatibility and has become a viable alternative to more traditional modifications, such as direct polymer conjugation. Furthermore, certain bioactive molecules can be immobilized onto the surface of phospholipid platforms to generate displays more reminiscent of cellular surface components. Thus, NPs with membrane-mimetic displays have found use in a range of bioimaging, biosensing, and drug delivery applications. This review herein describes recent advances in the preparations and characterization of integrated functional NPs covered by artificial cell membrane structures and their use in various biomedical applications. PMID:23688632

The Expanded FindCore Method for Identification of a Core Atom Set for Assessment of Protein Structure Prediction

Science.gov (United States)

Snyder, David A.; Grullon, Jennifer; Huang, Yuanpeng J.; Tejero, Roberto; Montelione, Gaetano T.

2014-01-01

Maximizing the scientific impact of NMR-based structure determination requires robust and statistically sound methods for assessing the precision of NMR-derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR-derived structures as targets in the CASP competition. FindCore (D.A. Snyder and G.T. Montelione PROTEINS 2005;59:673–686) is a superimposition independent method for identifying a core atom set, and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not-well-defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an “Expanded FindCore” atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well-defined regions of 18 NMR-derived CASP10 target structures. The Expanded FindCore protocol defines “expanded core atom sets” that match an expert’s intuition of which parts of the structure are sufficiently well-defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores. PMID:24327305

Systems Biology

Indian Academy of Sciences (India)

IAS Admin

study and understand the function of biological systems, particu- larly, the response of such .... understand the organisation and behaviour of prokaryotic sys- tems. ... relationship of the structure of a target molecule to its ability to bind a certain ...

Metagenome of a Versatile Chemolithoautotroph from Expanding Oceanic Dead Zones

Energy Technology Data Exchange (ETDEWEB)

Walsh, David A.; Zaikova, Elena; Howes, Charles L.; Song, Young; Wright, Jody; Tringe, Susannah G.; Tortell, Philippe D.; Hallam, Steven J.

2009-07-15

Oxygen minimum zones (OMZs), also known as oceanic"dead zones", are widespread oceanographic features currently expanding due to global warming and coastal eutrophication. Although inhospitable to metazoan life, OMZs support a thriving but cryptic microbiota whose combined metabolic activity is intimately connected to nutrient and trace gas cycling within the global ocean. Here we report time-resolved metagenomic analyses of a ubiquitous and abundant but uncultivated OMZ microbe (SUP05) closely related to chemoautotrophic gill symbionts of deep-sea clams and mussels. The SUP05 metagenome harbors a versatile repertoire of genes mediating autotrophic carbon assimilation, sulfur-oxidation and nitrate respiration responsive to a wide range of water column redox states. Thus, SUP05 plays integral roles in shaping nutrient and energy flow within oxygen-deficient oceanic waters via carbon sequestration, sulfide detoxification and biological nitrogen loss with important implications for marine productivity and atmospheric greenhouse control.

Evaluation of functionality and biological response of the multilayer flow modulator in porcine animal models.

Science.gov (United States)

Sultan, Sherif; Kavanagh, Edel P; Hynes, Niamh; Diethrich, Edward B

2016-02-01

This study outlines the use of non-aneurysmal porcine animal models to study device functionality and biological response of the Multilayer Flow Modulator (MFM) (Cardiatis, Isnes, Belgium), with an emphasis on preclinical device functionality and biological response characteristics in an otherwise healthy aorta. Twelve animals were implanted with the study device in the abdominal aorta, in 6 animals for 1 month and 6 animals for 6 months. Upon completion of the study period, each animal underwent a necropsy to examine how the implanted device had affected the artery and surrounding tissue. Neointima and stenosis formation were recorded via morphometry, and endothelialization via histopathological analysis. The MFM devices were delivered to their respective implantation sites without difficulty. Six of the implanted stents were oversized with percentages ranging from 2.6% to 18.8%. Statistical analysis was carried out and showed no significance between the regular sized stent group and oversized stent group for neointimal area (P=0.17), neointimal thickness (P=0.17), and percentage area stenosis (P=0.65). Histopathological findings showed in most areas flattened endothelium like cells lined the luminal surface of the neointima. Scanning electron microscopy also showed the devices were well tolerated, inciting only a minimal neointimal covering and little fibrin or platelet deposition. Neointimal thickness of 239.7±55.6 μm and 318.3±130.4 μm, and percentage area stenosis of 9.6±2.6% and 12.6±5% were recorded at 1 and 6 months respectively. No statistical differences were found between these results. The MFM devices were delivered to their respective implantation sites without difficulty and incited little neointimal and stenosis formation in the aorta, affirming its functionality and biocompatibility.

Systems biology of human metabolism - Defining the epithelial to mesenchymal transition and the activity of human gluconokinase

OpenAIRE

Rohatgi, Neha

2016-01-01

Studying human metabolism is crucial for the understanding of diseases and improvement of therapy as metabolic alterations are central to a number of human diseases. A variety of experimental disciplines, such as biochemistry, biophysics and systems biology are involved in the elucidation of metabolic pathways. The work presented in this thesis is divided into three main studies, which expand the knowledge of human metabolism using systems biology and biochemical techniques....

Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

Science.gov (United States)

De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

2010-03-01

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions.

Science.gov (United States)

Vernon, Ian; Liu, Junli; Goldstein, Michael; Rowe, James; Topping, Jen; Lindsey, Keith

2018-01-02

Many mathematical models have now been employed across every area of systems biology. These models increasingly involve large numbers of unknown parameters, have complex structure which can result in substantial evaluation time relative to the needs of the analysis, and need to be compared to observed data of various forms. The correct analysis of such models usually requires a global parameter search, over a high dimensional parameter space, that incorporates and respects the most important sources of uncertainty. This can be an extremely difficult task, but it is essential for any meaningful inference or prediction to be made about any biological system. It hence represents a fundamental challenge for the whole of systems biology. Bayesian statistical methodology for the uncertainty analysis of complex models is introduced, which is designed to address the high dimensional global parameter search problem. Bayesian emulators that mimic the systems biology model but which are extremely fast to evaluate are embeded within an iterative history match: an efficient method to search high dimensional spaces within a more formal statistical setting, while incorporating major sources of uncertainty. The approach is demonstrated via application to a model of hormonal crosstalk in Arabidopsis root development, which has 32 rate parameters, for which we identify the sets of rate parameter values that lead to acceptable matches between model output and observed trend data. The multiple insights into the model's structure that this analysis provides are discussed. The methodology is applied to a second related model, and the biological consequences of the resulting comparison, including the evaluation of gene functions, are described. Bayesian uncertainty analysis for complex models using both emulators and history matching is shown to be a powerful technique that can greatly aid the study of a large class of systems biology models. It both provides insight into model behaviour

Multi-functional photonic crystal sensors enabled by biological silica (Conference Presentation)

Science.gov (United States)

Wang, Alan X.

2017-02-01

Diatoms are microalgae found in every habitat where water is present. They produce 40% of the ocean's yearly production of organic carbon and 20% of the oxygen that we breathe. Their abundance and wide distribution make them ideal materials for a wide range of applications as living organisms. In our previous work, we have demonstrated that diatom biosilica with self-assembled silver nanoparticles (Ag NPs) can be used as ultra-sensitive, low-cost substrates for surface-enhanced Raman scattering (SERS) sensing. The enhancement comes from the photonic crystal enhancement of diatom frustules that could improve the hot-spots of Ag NPs. In this work, we report the unique micro-fluidic flow, analyte concentration effect, and thin layer chromatography (TLC) on diatom biosilica, which enables selection, separation, detection, and analysis of complex chemical and biological samples. Particularly, we show that the microscopic fluidic flow induced by the evaporation of liquid droplet can concentrate the analyte and achieve label-free sensing of single molecule detection of R6G and label-free sensing of 4.5×10-17g trinitrotoluene (TNT) from only 200 nano-liter solution. We also demonstrated a facile method for instant on-site separation and detection of analytes by TLC in tandem with SERS spectroscopy using high density diatom thin film. This lab-on-chip technology has been successfully applied for label-free detection of polycyclic aromatic hydrocarbons from human plasma and histamine from salmon fish. Our research suggests that such cost-effective, multi-functional photonic crystal sensors enabled by diatom biosilica opens a new route for lab-on-chip systems and possess significant engineering potentials for chemical and biological sensing.

Constrained multi-objective optimization of radial expanders in organic Rankine cycles by firefly algorithm

International Nuclear Information System (INIS)

Bahadormanesh, Nikrouz; Rahat, Shayan; Yarali, Milad

2017-01-01

Highlights: • A multi-objective optimization for radial expander in Organic Rankine Cycles is implemented. • By using firefly algorithm, Pareto front based on the size of turbine and thermal efficiency is produced. • Tension and vibration constrains have a significant effect on optimum design points. - Abstract: Organic Rankine Cycles are viable energy conversion systems in sustainable energy systems due to their compatibility with low-temperature heat sources. In the present study, one dimensional model of radial expanders in conjunction with a thermodynamic model of organic Rankine cycles is prepared. After verification, by defining thermal efficiency of the cycle and size parameter of a radial turbine as the objective functions, a multi-objective optimization was conducted regarding tension and vibration constraints for 4 different organic working fluids (R22, R245fa, R236fa and N-Pentane). In addition to mass flow rate, evaporator temperature, maximum pressure of cycle and turbo-machinery design parameters are selected as the decision variables. Regarding Pareto fronts, by a little increase in size of radial expanders, it is feasible to reach high efficiency. Moreover, by assessing the distribution of decision variables, the variables that play a major role in trending between the objective functions are found. Effects of mechanical and vibration constrains on optimum decision variables are investigated. The results of optimization can be considered as an initial values for design of radial turbines for Organic Rankine Cycles.

Oxidative metabolites of lycopene and their biological functions

Science.gov (United States)

To gain a better understanding of the beneficial biological activities of lycopene on cancer prevention, a greater knowledge of the metabolism of lycopene is needed. In particular, the identification of lycopene metabolites and oxidation products in vivo; the importance of tissue specific lycopene c...

An integrative approach to inferring biologically meaningful gene modules

Directory of Open Access Journals (Sweden)

Wang Kai

2011-07-01

Full Text Available Abstract Background The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO annotation in construction of gene modules in order to gain better functional association. Results We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions. Conclusions The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.

Functionalized amphipols

DEFF Research Database (Denmark)

Della Pia, Eduardo Antonio; Hansen, Randi Westh; Zoonens, Manuela

2014-01-01

Amphipols are amphipathic polymers that stabilize membrane proteins isolated from their native membrane. They have been functionalized with various chemical groups in the past years for protein labeling and protein immobilization. This large toolbox of functionalized amphipols combined with their...... surfaces for various applications in synthetic biology. This review summarizes the properties of functionalized amphipols suitable for synthetic biology approaches....

Synthetic Biology Open Language Visual (SBOL Visual) Version 2.0

KAUST Repository

Cox, Robert Sidney; Madsen, Curtis; McLaughlin, James; Nguyen, Tramy; Roehner, Nicholas; Bartley, Bryan; Bhatia, Swapnil; Bissell, Mike; Clancy, Kevin; Gorochowski, Thomas; Grunberg, Raik; Luna, Augustin; Le Novè re, Nicolas; Pocock, Matthew; Sauro, Herbert; Sexton, John T.; Stan, Guy-Bart; Tabor, Jeffrey J.; Voigt, Christopher A.; Zundel, Zach; Myers, Chris; Beal, Jacob; Wipat, Anil

2018-01-01

to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.0 of SBOL Visual, which builds on the prior SBOL Visual 1.0 standard by expanding diagram syntax to include functional interactions

A Conceptual Model to Identify Intent to Use Chemical-Biological Weapons

Directory of Open Access Journals (Sweden)

Mary Zalesny

2017-10-01

Full Text Available This paper describes a conceptual model to identify and interrelate indicators of intent of non-state actors to use chemical or biological weapons. The model expands on earlier efforts to understand intent to use weapons of mass destruction by building upon well-researched theories of intent and behavior and focusing on a sub-set of weapons of mass destruction (WMD to account for the distinct challenges of employing different types of WMD in violent acts. The conceptual model is presented as a first, critical step in developing a computational model for assessing the potential for groups to use chemical or biological weapons.

Origin and dynamics of expanding neutral hydrogen supershells

International Nuclear Information System (INIS)

Kolesnik, I.G.; Silich, S.A.

1987-01-01

The evolutionary model of expanding supershells regulated by induced star formation is proposed. It is suggested that giant expanding shells are formed n superclouds at late evolutionary stage of star complexes. To understand the dynamics of the most huge supershells it is necessary to take into account that expanding shells can trigger star formation in cold dense pre-exosting cloudlets. Efficiency of induced star formation must be less than one percent to fit observational properties of supershells

Treatment of relapsing polychondritis in the era of biological agents.

LENUS (Irish Health Repository)

McCarthy, Eoghan M

2012-02-01

Relapsing polychondritis (RP) is a rare disorder, often requiring high doses of immunosuppressive therapy to control its potentially life-threatening consequences. The advent of biological agents has added to the armamentarium available to treat RP, but the lack of controlled trials, along with the small numbers of patients and disease heterogeneity means that new therapies are prescribed without the benefits of rigorous clinical research. Thus, information on individual cases is of value in expanding our knowledge of the use of biologic agents in rare conditions. We report on the use of rituximab in a patient who subsequently developed catastrophic aortic incompetence, and we review the literature in relation to the use of this drug in RP.

Paradigms for biologically inspired design

DEFF Research Database (Denmark)

Lenau, T. A.; Metzea, A.-L.; Hesselberg, T.

2018-01-01

engineering, medical engineering, nanotechnology, photonics,environmental protection and agriculture. However, a major obstacle for the wider use of biologically inspired design isthe knowledge barrier that exist between the application engineers that have insight into how to design suitable productsand......Biologically inspired design is attracting increasing interest since it offers access to a huge biological repository of wellproven design principles that can be used for developing new and innovative products. Biological phenomena can inspireproduct innovation in as diverse areas as mechanical...... the biologists with detailed knowledge and experience in understanding how biological organisms function in theirenvironment. The biologically inspired design process can therefore be approached using different design paradigmsdepending on the dominant opportunities, challenges and knowledge characteristics...

Comparison of expandable endotracheal stents in the treatment of surgically induced piglet tracheomalacia.

Science.gov (United States)

Mair, E A; Parsons, D S; Lally, K P; Van Dellen, A F

1991-09-01

Present surgical alternatives for pediatric tracheobronchomalacia are limited and associated with many potentially undesirable complications. The feasibility of different intraluminal expandable endotracheal stents for the treatment of surgically induced tracheomalacia was analyzed in 27 piglets. A potentially fatal tracheomalacia was surgically created. Either a stainless steel "zig-zag" stent or a woven polymeric stent was then implanted. Tracheal patency, mucosal function, histopathologic respiratory tract changes, and effects of the stent on esophageal motility were evaluated over a 16-week period. Piglets with steel stents uniformly experienced intense inflammation leading to tracheal dysfunction and death. Piglets with polymeric stents experienced minimal respiratory symptoms. Expandable polymeric endotracheal stents alleviate surgically induced piglet tracheomalacia, were easy to insert, allowed for tracheal growth, and reduced the need for high-risk surgical procedures with prolonged ventilatory support.

Seal-less cryogenic expander

International Nuclear Information System (INIS)

Faria, L.E.; Christopher, E.H.

1987-01-01

In an expander for use in a split Stirling cycle refrigeration system of the type wherein a displacer moves with reciprocating motion inside an expander housing, and wherein a plunger force and a regenerator force are formed on the displacer, the plunger force cyclically varying and having a time of minimum and maximum plunger force amplitude, and the regenerator force cyclically varying and having a time of minimum and maximum regenerator force amplitude, the improvement is described comprising: (a) means for maintaining displacer forces, such that the maximum plunger force amplitude is substantially equal to the maximum regenerator force amplitude; and (b) means for adjusting a time difference, the time difference being the time between the time of maximum plunger force and the time of maximum regenerator force such that a measure of the cooling power of the refrigeration system is maximized

The RNAi Universe in Fungi: A Varied Landscape of Small RNAs and Biological Functions.

Science.gov (United States)

Torres-Martínez, Santiago; Ruiz-Vázquez, Rosa M

2017-09-08

RNA interference (RNAi) is a conserved eukaryotic mechanism that uses small RNA molecules to suppress gene expression through sequence-specific messenger RNA degradation, translational repression, or transcriptional inhibition. In filamentous fungi, the protective function of RNAi in the maintenance of genome integrity is well known. However, knowledge of the regulatory role of RNAi in fungi has had to wait until the recent identification of different endogenous small RNA classes, which are generated by distinct RNAi pathways. In addition, RNAi research on new fungal models has uncovered the role of small RNAs and RNAi pathways in the regulation of diverse biological functions. In this review, we give an up-to-date overview of the different classes of small RNAs and RNAi pathways in fungi and their roles in the defense of genome integrity and regulation of fungal physiology and development, as well as in the interaction of fungi with biotic and abiotic environments.

Semiclassical expanding discrete space-times

International Nuclear Information System (INIS)

Cobb, W.K.; Smalley, L.L.

1981-01-01

Given the close ties between general relativity and geometry one might reasonably expect that quantum effects associated with gravitation might also be tied to the geometry of space-time, namely, to some sort of discreteness in space-time itself. In particular it is supposed that space-time consists of a discrete lattice of points rather than the usual continuum. Since astronomical evidence seems to suggest that the universe is expanding, the lattice must also expand. Some of the implications of such a model are that the proton should presently be stable, and the universe should be closed although the mechanism for closure is quantum mechanical. (author)

Physics and biology

International Nuclear Information System (INIS)

Frauenfelder, H.

1988-01-01

The author points out that the coupling between physics and biology is becoming closer as time goes on. He tries to show that physical studies on biological systems not only yield insight into biology but also provide results of interest to physics. Biological systems are extremly complex system. Ideally one would like to understand the behavior of such systems in terms of the behavior of its constituent atoms. Since in small organisms this may be 10 20 atoms, it is clear these are not simple many-body systems. He reviews the basic elements of cells and then considers the broader questions of structure, complexity, and function, which must be looked at on levels from the cell to the organism. Despite the vast amount of observational material already in existence, biophysics and biological physics are only at a beginning. We can expect that physics will continue to interact strongly with biology. Actually, the connection also includes chemistry and mathematics. New tools that become available in physics will continue to be applied to biological problems. We can expect that the flow of information will not be one way; biological systems will provide new information on many old and new parts of physics, from reaction theory and transport phenomena to complexity, cooperativity, and nonlinear processes

Integrated Biological Control

International Nuclear Information System (INIS)

JOHNSON, A.R.

2002-01-01

Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response

Refrigeration generation using expander-generator units

Science.gov (United States)

Klimenko, A. V.; Agababov, V. S.; Koryagin, A. V.; Baidakova, Yu. O.

2016-05-01

The problems of using the expander-generator unit (EGU) to generate refrigeration, along with electricity were considered. It is shown that, on the level of the temperatures of refrigeration flows using the EGU, one can provide the refrigeration supply of the different consumers: ventilation and air conditioning plants and industrial refrigerators and freezers. The analysis of influence of process parameters on the cooling power of the EGU, which depends on the parameters of the gas expansion process in the expander and temperatures of cooled environment, was carried out. The schematic diagram of refrigeration generation plant based on EGU is presented. The features and advantages of EGU to generate refrigeration compared with thermotransformer of steam compressive and absorption types were shown, namely: there is no need to use the energy generated by burning fuel to operate the EGU; beneficial use of the heat delivered to gas from the flow being cooled in equipment operating on gas; energy production along with refrigeration generation, which makes it possible to create, using EGU, the trigeneration plants without using the energy power equipment. It is shown that the level of the temperatures of refrigeration flows, which can be obtained by using the EGU on existing technological decompression stations of the transported gas, allows providing the refrigeration supply of various consumers. The information that the refrigeration capacity of an expander-generator unit not only depends on the parameters of the process of expansion of gas flowing in the expander (flow rate, temperatures and pressures at the inlet and outlet) but it is also determined by the temperature needed for a consumer and the initial temperature of the flow of the refrigeration-carrier being cooled. The conclusion was made that the expander-generator units can be used to create trigeneration plants both at major power plants and at small energy.

From biological and social network metaphors to coupled bio-social wireless networks

Science.gov (United States)

Barrett, Christopher L.; Eubank, Stephen; Anil Kumar, V.S.; Marathe, Madhav V.

2010-01-01

Biological and social analogies have been long applied to complex systems. Inspiration has been drawn from biological solutions to solve problems in engineering products and systems, ranging from Velcro to camouflage to robotics to adaptive and learning computing methods. In this paper, we present an overview of recent advances in understanding biological systems as networks and use this understanding to design and analyse wireless communication networks. We expand on two applications, namely cognitive sensing and control and wireless epidemiology. We discuss how our work in these two applications is motivated by biological metaphors. We believe that recent advances in computing and communications coupled with advances in health and social sciences raise the possibility of studying coupled bio-social communication networks. We argue that we can better utilise the advances in our understanding of one class of networks to better our understanding of the other. PMID:21643462

Extracellular matrix hydrogels from decellularized tissues: Structure and function.

Science.gov (United States)

Saldin, Lindsey T; Cramer, Madeline C; Velankar, Sachin S; White, Lisa J; Badylak, Stephen F

2017-02-01

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed. More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chemistry and biology by new multiple choice

International Nuclear Information System (INIS)

Seo, Hyeong Seok; Kim, Seong Hwan

2003-02-01

This book is divided into two parts, the first part is about chemistry, which deals with science of material, atom structure and periodic law, chemical combination and power between molecule, state of material and solution, chemical reaction and an organic compound. The second part give description of biology with molecule and cell, energy in cells and chemical synthesis, molecular biology and heredity, function on animal, function on plant and evolution and ecology. This book has explanation of chemistry and biology with new multiple choice.

Excited states in biological systems

International Nuclear Information System (INIS)

Cilento, G.; Zinner, K.; Bechara, E.J.H.; Duran, N.; Baptista, R.C. de; Shimizu, Y.; Augusto, O.; Faljoni-Alario, A.; Vidigal, C.C.C.; Oliveira, O.M.M.F.; Haun, M.

1979-01-01

Some aspects of bioluminescence related to bioenergetics are discussed: 1. chemical generation of excited species, by means of two general processes: electron transference and cyclic - and linear peroxide cleavage; 2. biological systems capable of generating excited states and 3. biological functions of these states, specially the non-emissive ones (tripletes). The production and the role of non-emissive excited states in biological systems are analysed, the main purpose of the study being the search for non-emissive states. Experiences carried out in biological systems are described; results and conclusions are given. (M.A.) [pt

IL-15/IL-15 receptor biology: a guided tour through an expanding universe.

Science.gov (United States)

Budagian, Vadim; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia

2006-08-01

The cytokine interleukin-15 (IL-15) has a key role in promoting survival, proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its functional similarities to IL-2, IL-15 affects a wider range of target cell populations and utilizes different mechanisms of signaling. Here, we review recent advances in the IL-15-mediated signaling, and in the functional properties on cells besides T lymphocytes and NK cells. These are discussed in the context of their potential clinical and therapeutic relevance.

Molecular dynamics simulation studies of transmembrane transport of chemical components in Chinese herbs and the function of platycodin D in a biological membrane

Directory of Open Access Journals (Sweden)

Shufang Yang

2017-04-01

Conclusion: The Martini force field was successfully applied to the study of the interaction between herbal compounds and a biological membrane. By combining the dynamics equilibrium morphology, the distribution of drugs inside and outside the biomembrane, and the interaction sites of drugs on the DPPC bilayer, factors influencing transmembrane transport of drugs were elucidated and the function of platycodin D in a biological membrane was reproduced.

Dual Causality and the Autonomy of Biology.

Science.gov (United States)

Bock, Walter J

2017-03-01

Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.

Structural Elucidation and Biological Activity of a Highly Regular Fucosylated Glycosaminoglycan from the Edible Sea Cucumber Stichopus herrmanni.

Science.gov (United States)

Li, Xiaomei; Luo, Lan; Cai, Ying; Yang, Wenjiao; Lin, Lisha; Li, Zi; Gao, Na; Purcell, Steven W; Wu, Mingyi; Zhao, Jinhua

2017-10-25

Edible sea cucumbers are widely used as a health food and medicine. A fucosylated glycosaminoglycan (FG) was purified from the high-value sea cucumber Stichopus herrmanni. Its physicochemical properties and structure were analyzed and characterized by chemical and instrumental methods. Chemical analysis indicated that this FG with a molecular weight of ∼64 kDa is composed of N-acetyl-d-galactosamine, d-glucuronic acid (GlcA), and l-fucose. Structural analysis clarified that the FG contains the chondroitin sulfate E-like backbone, with mostly 2,4-di-O-sulfated (85%) and some 3,4-di-O-sulfated (10%) and 4-O-sulfated (5%) fucose side chains that link to the C3 position of GlcA. This FG is structurally highly regular and homogeneous, differing from the FGs of other sea cucumbers, for its sulfation patterns are simpler. Biological activity assays indicated that it is a strong anticoagulant, inhibiting thrombin and intrinsic factor Xase. Our results expand the knowledge on structural types of FG and illustrate its biological activity as a functional food material.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

Directory of Open Access Journals (Sweden)

Rinaldo Florencio-Silva

2015-01-01

Full Text Available Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines and systemic (e.g., calcitonin and estrogens factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality

International Nuclear Information System (INIS)

Ling, C. Clifton; Humm, John; Larson, Steven; Amols, Howard; Fuks, Zvi; Leibel, Steven; Koutcher, Jason A.

2000-01-01

Purpose: The goals of this study were to survey and summarize the advances in imaging that have potential applications in radiation oncology, and to explore the concept of integrating physical and biological conformality in multidimensional conformal radiotherapy (MD-CRT). Methods and Materials: The advances in three-dimensional conformal radiotherapy (3D-CRT) have greatly improved the physical conformality of treatment planning and delivery. The development of intensity-modulated radiotherapy (IMRT) has provided the 'dose painting' or 'dose sculpting' ability to further customize the delivered dose distribution. The improved capabilities of nuclear magnetic resonance imaging and spectroscopy, and of positron emission tomography, are beginning to provide physiological and functional information about the tumor and its surroundings. In addition, molecular imaging promises to reveal tumor biology at the genotype and phenotype level. These developments converge to provide significant opportunities for enhancing the success of radiotherapy. Results: The ability of IMRT to deliver nonuniform dose patterns by design brings to fore the question of how to 'dose paint' and 'dose sculpt', leading to the suggestion that 'biological' images may be of assistance. In contrast to the conventional radiological images that primarily provide anatomical information, biological images reveal metabolic, functional, physiological, genotypic, and phenotypic data. Important for radiotherapy, the new and noninvasive imaging methods may yield three-dimensional radiobiological information. Studies are urgently needed to identify genotypes and phenotypes that affect radiosensitivity, and to devise methods to image them noninvasively. Incremental to the concept of gross, clinical, and planning target volumes (GTV, CTV, and PTV), we propose the concept of 'biological target volume' (BTV) and hypothesize that BTV can be derived from biological images and that their use may incrementally improve

Second Generation Self-Inflating Tissue Expanders: A Two-Year Experience

Directory of Open Access Journals (Sweden)

Jamal Omran Al Madani

2014-01-01

Full Text Available Background. Tissue expansion is a well-established surgical technique that produces an additional amount of normal skin to cover a defect. This technique is appealing because the skin quality and color are from the patient’s own. The widely used injectable expanders are of great reliability but carry the disadvantage of being painful during injection and most of the time require multiple clinic visits. So the idea of self-inflation became attractive and hydrogel expanders were developed and became widely known for being painless during clinic visit and decrease number of visits. The first generation expanders were modified by adding an enclosing plastic shell to decrease the unopposed expansion that occurred in the first generation expanders, which lead to pressure necrosis of the skin flaps. This made it an attractive option for tissue expansion in children and some adult patients. Patients, Materials, and Methods. Charts of 17 patients were retrospectively reviewed, all of them had second generation self-inflating expanders implanted over a 2-year period for one of two purposes, the treatment of giant nevi or burn scars. Results. Fifteen patients were females and 2 were males. The indication was large burn scar in 14 cases (14/17, in which 47/55 expanders were implanted, and giant nevus in 3/17 cases in which 8/55 expanders were implanted. Extrusion of the expander occurred in 8/55 expanders (14.5%, which occurred in 6/14 patients. The highest percentage of extrusion occurred in the neck in which two out of three expanders extruded; otherwise this complication does not seem to be related to the indication, gender, nor age of the patients. It seems to be that it is technical in nature. The patients did not have to get any injections to fill the tissue expanders, which made the expansion process less painful and more convenient. Conclusion. This seems to be currently the largest published review in which second generation expanders were used

Synthesis, characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles

International Nuclear Information System (INIS)

Bhattacharya, Dipsikha; Sahu, Sumanta K.; Banerjee, Indranil; Das, Manasmita; Mishra, Debashish; Maiti, Tapas K.; Pramanik, Panchanan

2011-01-01

In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T 2 contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T 2 relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.

Physics of biological membranes

Science.gov (United States)

Mouritsen, Ole G.

The biological membrane is a complex system consisting of an aqueous biomolecular planar aggregate of predominantly lipid and protein molecules. At physiological temperatures, the membrane may be considered a thin (˜50Å) slab of anisotropic fluid characterized by a high lateral mobility of the various molecular components. A substantial fraction of biological activity takes place in association with membranes. As a very lively piece of condensed matter, the biological membrane is a challenging research topic for both the experimental and theoretical physicists who are facing a number of fundamental physical problems including molecular self-organization, macromolecular structure and dynamics, inter-macromolecular interactions, structure-function relationships, transport of energy and matter, and interfacial forces. This paper will present a brief review of recent theoretical and experimental progress on such problems, with special emphasis on lipid bilayer structure and dynamics, lipid phase transitions, lipid-protein and lipid-cholesterol interactions, intermembrane forces, and the physical constraints imposed on biomembrane function and evolution. The paper advocates the dual point of view that there are a number of interesting physics problems in membranology and, at the same time, that the physical properties of biomembranes are important regulators of membrane function.

Genome-wide association study and biological pathway analysis for response to Eimeria maxima in broilers

DEFF Research Database (Denmark)

Hamzic, Edin; Buitenhuis, Albert Johannes; Hérault, Frédéric

2015-01-01

Background Coccidiosis is the most common and costly disease in the poultry industry and which caused by protozoans from the genus of Eimeria. The current control of coccidiosis, based on the use of anticoccidial drugs and vaccination, faces serious obstacles such as drug resistance and the high...... costs for development of efficient vaccines, respectively. Therefore, the present control programs must be expanded with complementary approaches such as the use of genetics for improvement of the host’s response to Eimeria infections. Recently, we have performed a large-scale challenge study on Cobb500...... of the measured traits in the response to Eimeria maxima in broilers. Furthermore, we conducted a post-GWAS functional analysis with the aim of gaining a better biological understanding of the underlying response to Eimeria maxima challenge in broilers. Results In total, we identified 22 single nucleotide...

Assessing biological invasions in European Seas: Biological traits of the most widespread non-indigenous species

Science.gov (United States)

Cardeccia, Alice; Marchini, Agnese; Occhipinti-Ambrogi, Anna; Galil, Bella; Gollasch, Stephan; Minchin, Dan; Narščius, Aleksas; Olenin, Sergej; Ojaveer, Henn

2018-02-01

The biological traits of the sixty-eight most widespread multicellular non-indigenous species (MWNIS) in European Seas: Baltic Sea, Western European Margin of the Atlantic Ocean and the Mediterranean Sea were examined. Data for nine biological traits was analyzed, and a total of 41 separate categories were used to describe the biological and ecological functions of these NIS. Our findings show that high dispersal ability, high reproductive rate and ecological generalization are the biological traits commonly associated with MWNIS. The functional groups that describe most of the 68 MWNIS are: photoautotrophic, zoobenthic (both sessile and motile) and nektonic predatory species. However, these 'most widespread' species comprise a wide range of taxa and biological trait profiles; thereby a clear "identikit of a perfect invader" for marine and brackish environments is difficult to define. Some traits, for example: "life form", "feeding method" and "mobility", feature multiple behaviours and strategies. Even species introduced by a single pathway, e.g. vessels, feature diverse biological trait profiles. MWNIS likely to impact community organization, structure and diversity are often associated with brackish environments. For many traits ("life form", "sociability", "reproductive type", "reproductive frequency", "haploid and diploid dispersal" and "mobility"), the categories mostly expressed by the impact-causing MWNIS do not differ substantially from the whole set of MWNIS.

Strength analysis of expandable tubulars for well applications

Energy Technology Data Exchange (ETDEWEB)

Aguiar, A.C.C. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Fonseca, C.E. [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil); Netto, T.A. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE)

2008-07-01

Solid expandable tube technology has many advantages when compared to conventional wells. The expansion of tubes in situ allows developing reserves in many of the challenging scenarios found in oil industry, as pre-salt layer, HPHT wells, deep reservoirs, or ultra-deep water. Besides, this procedure has good compatibility with directional and horizontal wells and facilitates side-tracks operations. Although the expansion of tubes is very attractive, a better understanding of its influence on the tube mechanical strength is necessary. In this work, experimental tests and numerical analyses were performed in order to determine the effect of parameters such as diameter-to-thickness ratio and expansion rate on the collapse resistance of expandable tubes. An experimental apparatus was designed and built to reproduce full-scale tube expansion. Three 2 meter long specimens were expanded 10% their original diameters and subjected to hydrostatic pressure inside a vessel until collapse. Three non-expanded tubes were also tested for comparison. At the same time, non-linear numerical models were developed using the finite element method. After calibration, they were used to further analyze the mechanical behavior of solid expandable tubes and the influence of expansion on its resistance against collapse. (author)

Structures of Adnectin/Protein Complexes Reveal an Expanded Binding Footprint

Energy Technology Data Exchange (ETDEWEB)

Ramamurthy, Vidhyashankar; Krystek, Jr., Stanley R.; Bush, Alexander; Wei, Anzhi; Emanuel, Stuart L.; Gupta, Ruchira Das; Janjua, Ahsen; Cheng, Lin; Murdock, Melissa; Abramczyk, Bozena; Cohen, Daniel; Lin, Zheng; Morin, Paul; Davis, Jonathan H.; Dabritz, Michael; McLaughlin, Douglas C.; Russo, Katie A.; Chao, Ginger; Wright, Martin C.; Jenny, Victoria A.; Engle, Linda J.; Furfine, Eric; Sheriff, Steven (BMS)

2014-10-02

Adnectins are targeted biologics derived from the tenth type III domain of human fibronectin ({sup 10}Fn3), a member of the immunoglobulin superfamily. Target-specific binders are selected from libraries generated by diversifying the three {sup 10}Fn3 loops that are analogous to the complementarity determining regions of antibodies. The crystal structures of two Adnectins were determined, each in complex with its therapeutic target, EGFR or IL-23. Both Adnectins bind different epitopes than those bound by known monoclonal antibodies. Molecular modeling suggests that some of these epitopes might not be accessible to antibodies because of the size and concave shape of the antibody combining site. In addition to interactions from the Adnectin diversified loops, residues from the N terminus and/or the {beta} strands interact with the target proteins in both complexes. Alanine-scanning mutagenesis confirmed the calculated binding energies of these {beta} strand interactions, indicating that these nonloop residues can expand the available binding footprint.

Roll-expanded plugs for steam generator heating tubes verification of leak tightness over the component lifetime

International Nuclear Information System (INIS)

Beck, J.; Ziegler, R.; Schönheit, N.

2013-01-01

Highlights: • Design description of roll-expanded plugs. • Experimental simulation of 40 years lifetime of plugged steam generator tubes. • Destructive testing for off-design loads. • Evaluation of release pressure and tightness before and after the tests. -- Abstract: Steam generator heating tubes are the boundary between the irradiated primary cycle and the conventional secondary cycle in a pressurized water reactor. Despite their operational task to transfer the heat from the primary to the secondary cycle, these tubes have a crucial safety function: the retention of irradiated primary coolant inside the circuit in all operating, emergency and off-design conditions. The heating tubes are subject to various degradation mechanisms during operation. To verify the integrity of each single tube, nuclear power plants carry out frequent in-service inspections. In case of a tube wall degradation beyond the permissible limit, the tube needs to be taken out of service in order to maintain the overall component integrity. The most common method to do so is to plug a damaged tube by a roll-expanded plug. After plugging, the roll-expanded plug acts as pressure boundary between the primary and the secondary cycle instead of the damaged heating tube. The plug must be able to maintain this function, previously provided by the heating tube, in all operational, emergency and off-design conditions. This article describes the approach to this verification by launching several comprehensive process qualification programmes consisting of mechanical analyses as well as static and dynamic testing programmes. The result was a qualified roll-expanded plug which remains leak-tight even during off-design conditions

An Isothermal Steam Expander for an Industrial Steam Supplying System

Directory of Open Access Journals (Sweden)

Chen-Kuang Lin

2015-01-01

Full Text Available Steam is an essential medium used in the industrial process. To ensure steam quality, small and middle scale boilers are often adopted. However, because a higher steam pressure (compared to the necessary steam pressure is generated, the boiler’s steam pressure will be reduced via a pressure regulator before the steam is directed through the process. Unfortunately, pressure is somewhat wasted during the reducing process. Therefore, in order to promote energy efficiency, a pressure regulator is replaced by a steam expander. With this steam expander, the pressure will be transformed into mechanical energy and extracted during the expansion process. A new type of isothermal steam expander for an industrial steam supplying system will be presented in the paper. The isothermal steam expander will improve the energy efficiency of a traditional steam expander by replacing the isentropic process with an isothermal expansion process. With this, steam condensation will decrease, energy will increase, and steam quality will be improved. Moreover, the mathematical model of the isothermal steam expander will be established by using the Schmidt theory, the same principle used to analyze Stirling engines. Consequently, by verifying the correctness of the theoretical model for the isothermal steam expander using experimental data, a prototype of 100 c.c. isothermal steam expander is constructed.