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Sample records for modular multifunctional protein

  1. Protein Multifunctionality: Principles and Mechanisms

    PubMed Central

    Zaretsky, Joseph Z.; Wreschner, Daniel H.

    2008-01-01

    In the review, the nature of protein multifunctionality is analyzed. In the first part of the review the principles of structural/functional organization of protein are discussed. In the second part, the main mechanisms involved in development of multiple functions on a single gene product(s) are analyzed. The last part represents a number of examples showing that multifunctionality is a basic feature of biologically active proteins. PMID:21566747

  2. Multifunctional proteins revealed by overlapping clustering in protein interaction network

    PubMed Central

    Chapple, Charles E.; Guénoche, Alain; Brun, Christine

    2012-01-01

    Motivation: Multifunctional proteins perform several functions. They are expected to interact specifically with distinct sets of partners, simultaneously or not, depending on the function performed. Current graph clustering methods usually allow a protein to belong to only one cluster, therefore impeding a realistic assignment of multifunctional proteins to clusters. Results: Here, we present Overlapping Cluster Generator (OCG), a novel clustering method which decomposes a network into overlapping clusters and which is, therefore, capable of correct assignment of multifunctional proteins. The principle of OCG is to cover the graph with initial overlapping classes that are iteratively fused into a hierarchy according to an extension of Newman's modularity function. By applying OCG to a human protein–protein interaction network, we show that multifunctional proteins are revealed at the intersection of clusters and demonstrate that the method outperforms other existing methods on simulated graphs and PPI networks. Availability: This software can be downloaded from http://tagc.univ-mrs.fr/welcome/spip.php?rubrique197 Contact: brun@tagc.univ-mrs.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22080466

  3. [ALR, the multifunctional protein].

    PubMed

    Balogh, Tibor; Szarka, András

    2015-03-29

    ALR is a mystic protein. It has a so called "long" 22 kDa and a "short" 15 kDa forms. It has been described after partial hepatectomy and it has just been considered as a key protein of liver regeneration. At the beginning of the 21st century it has been revealed that the "long" form is localized in the mitochondrial intermembrane space and it is an element of the mitochondrial protein import and disulphide relay system. Several proteins of the substrates of the mitochondrial disulphide relay system are necessary for the proper function of the mitochondria, thus any mutation of the ALR gene leads to mitochondrial diseases. The "short" form of ALR functions as a secreted extracellular growth factor and it promotes the protection, regeneration and proliferation of hepatocytes. The results gained on the recently generated conditional ALR mutant mice suggest that ALR can play an important role in the pathogenesis of alcoholic and non-alcoholic steatosis. Since the serum level of ALR is modified in several liver diseases it can be a promising marker molecule in laboratory diagnostics. PMID:25796277

  4. Extreme multifunctional proteins identified from a human protein interaction network

    PubMed Central

    Chapple, Charles E.; Robisson, Benoit; Spinelli, Lionel; Guien, Céline; Becker, Emmanuelle; Brun, Christine

    2015-01-01

    Moonlighting proteins are a subclass of multifunctional proteins whose functions are unrelated. Although they may play important roles in cells, there has been no large-scale method to identify them, nor any effort to characterize them as a group. Here, we propose the first method for the identification of ‘extreme multifunctional' proteins from an interactome as a first step to characterize moonlighting proteins. By combining network topological information with protein annotations, we identify 430 extreme multifunctional proteins (3% of the human interactome). We show that the candidates form a distinct sub-group of proteins, characterized by specific features, which form a signature of extreme multifunctionality. Overall, extreme multifunctional proteins are enriched in linear motifs and less intrinsically disordered than network hubs. We also provide MoonDB, a database containing information on all the candidates identified in the analysis and a set of manually curated human moonlighting proteins. PMID:26054620

  5. The Coronavirus Nucleocapsid Is a Multifunctional Protein

    PubMed Central

    McBride, Ruth; van Zyl, Marjorie; Fielding, Burtram C.

    2014-01-01

    The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein. PMID:25105276

  6. Fabrication of modular multifunctional delivery for antitumor drugs based on host-guest recognition.

    PubMed

    Chen, Li; Zhang, Zhe; Chen, Xiaofei; Yao, Xuemei; He, Chaoliang; Chen, Xuesi

    2015-05-01

    Herein, learning from the idea of the modular concept widely used in ship building, as a design approach that assembles some subdivided smaller modules to a specific ship, a new modular multifunctional drug delivery (MMDD) with excellent biocompatibility was directly prepared by a flexible host-guest interaction between pH-sensitive benzimidazole-graft-dextran (Dex-BM) and pre-synthesized multifunctional cyclodextrins. In this drug system, pH-sensitive Dex-BM acted as the main case and pre-synthesized multifunctional cyclodextrins were the changeable modules. To verify the feasibility of MMDD in cancer chemotherapy, doxorubicin (DOX) was used as a model drug. In vitro drug release experiments indicated that the drug released around 80% from DOX-loaded MMDD at pH 5.3, while approximately 40% of DOX released under the condition of pH 7.4. Moreover, the targeting antitumor activity of DOX-loaded MMDD was investigated in HeLa and HepG2 cells using MTT assays, confocal laser scanning microscopy and flow cytometer, which indicated that the targeted DOX-loaded MMDD provided an efficient drug delivery platform for inhibition of different cancer cells. Meantime, the incorporation of different functional modules into one system was also investigated, simultaneously exhibiting targeting and imaging property. These features suggest that this modular multifunctional drug delivery system can efficiently enhance the inhibition of cellular proliferation in vitro, and according to the needs in clinical treatment, some targeting and imaging molecules can be chosen. PMID:25749295

  7. Multifunctional Microtubule-Associated Proteins in Plants

    PubMed Central

    Krtková, Jana; Benáková, Martina; Schwarzerová, Kateřina

    2016-01-01

    Microtubules (MTs) are involved in key processes in plant cells, including cell division, growth and development. MT-interacting proteins modulate MT dynamics and organization, mediating functional and structural interaction of MTs with other cell structures. In addition to conventional microtubule-associated proteins (MAPs) in plants, there are many other MT-binding proteins whose primary function is not related to the regulation of MTs. This review focuses on enzymes, chaperones, or proteins primarily involved in other processes that also bind to MTs. The MT-binding activity of these multifunctional MAPs is often performed only under specific environmental or physiological conditions, or they bind to MTs only as components of a larger MT-binding protein complex. The involvement of multifunctional MAPs in these interactions may underlie physiological and morphogenetic events, e.g., under specific environmental or developmental conditions. Uncovering MT-binding activity of these proteins, although challenging, may contribute to understanding of the novel functions of the MT cytoskeleton in plant biological processes. PMID:27148302

  8. Multifunctional protein: cardiac ankyrin repeat protein*

    PubMed Central

    Zhang, Na; Xie, Xiao-jie; Wang, Jian-an

    2016-01-01

    Cardiac ankyrin repeat protein (CARP) not only serves as an important component of muscle sarcomere in the cytoplasm, but also acts as a transcription co-factor in the nucleus. Previous studies have demonstrated that CARP is up-regulated in some cardiovascular disorders and muscle diseases; however, its role in these diseases remains controversial now. In this review, we will discuss the continued progress in the research related to CARP, including its discovery, structure, and the role it plays in cardiac development and heart diseases. PMID:27143260

  9. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins.

    PubMed

    Figueroa-Angulo, Elisa E; Calla-Choque, Jaeson S; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-01-01

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

  10. Toward Modular Analysis of Supramolecular Protein Assemblies.

    PubMed

    Kim, Jaehoon; Kim, Jin-Gyun; Yun, Giseok; Lee, Phill-Seung; Kim, Do-Nyun

    2015-09-01

    Despite recent advances in molecular simulation technologies, analysis of high-molecular-weight structures is still challenging. Here, we propose an automated model reduction procedure aiming to enable modular analysis of these structures. It employs a component mode synthesis for the reduction of finite element protein models. Reduced models may consist of real biological subunits or artificial partitions whose dynamics is described using the degrees of freedom at the substructural interfaces and a small set of dominant vibrational modes only. Notably, the proper number of dominant modes is automatically determined using a novel estimator for eigenvalue errors without calculating the reference eigensolutions of the full model. The performance of the proposed approach is thoroughly investigated by analyzing 50 representative structures including a crystal structure of GroEL and an electron density map of a ribosome. PMID:26575921

  11. Linker design for the modular assembly of multifunctional and targeted platinum(ii)-containing anticancer agents.

    PubMed

    Ding, S; Bierbach, U

    2016-08-16

    A versatile and efficient modular synthetic platform was developed for assembling multifunctional conjugates and targeted forms of platinum-(benz)acridines, a class of highly cytotoxic DNA-targeted hybrid agents. The synthetic strategy involved amide coupling between succinyl ester-modified platinum compounds (P1, P2) and a set of 11 biologically relevant primary and secondary amines (N1-N11). To demonstrate the feasibility and versatility of the approach, a structurally and functionally diverse range of amines was introduced. These include biologically active molecules, such as rucaparib (a PARP inhibitor), E/Z-endoxifen (an estrogen receptor antagonist), and a quinazoline-based tyrosine kinase inhibitor. Micro-scale reactions in Eppendorf tubes or on 96-well plates were used to screen for optimal coupling conditions in DMF solution with carbodiimide-, uronium-, and phosphonium-based compounds, as well as other common coupling reagents. Reactions with the phosphonium-based coupling reagent PyBOP produced the highest yields and gave the cleanest conversions. Furthermore, it was demonstrated that the chemistry can also be performed in aqueous media and is amenable to parallel synthesis based on multiple consecutive reactions in DMF in a "one-tube" format. In-line LC-MS was used to assess the stability of the conjugates in physiologically relevant buffers. Hydrolysis of the conjugates occurs at the ester moiety and is facilitated by the aquated metal moiety under low-chloride ion conditions. The rate of ester cleavage greatly depends on the nature of the amine component. Potential applications of the linker technology are discussed. PMID:27251881

  12. The modular architecture of protein-protein binding interfaces.

    PubMed

    Reichmann, D; Rahat, O; Albeck, S; Meged, R; Dym, O; Schreiber, G

    2005-01-01

    Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved. PMID:15618400

  13. Modularity in the evolution of yeast protein interaction network

    PubMed Central

    Ogishima, Soichi; Tanaka, Hiroshi; Nakaya, Jun

    2015-01-01

    Protein interaction networks are known to exhibit remarkable structures: scale-free and small-world and modular structures. To explain the evolutionary processes of protein interaction networks possessing scale-free and small-world structures, preferential attachment and duplication-divergence models have been proposed as mathematical models. Protein interaction networks are also known to exhibit another remarkable structural characteristic, modular structure. How the protein interaction networks became to exhibit modularity in their evolution? Here, we propose a hypothesis of modularity in the evolution of yeast protein interaction network based on molecular evolutionary evidence. We assigned yeast proteins into six evolutionary ages by constructing a phylogenetic profile. We found that all the almost half of hub proteins are evolutionarily new. Examining the evolutionary processes of protein complexes, functional modules and topological modules, we also found that member proteins of these modules tend to appear in one or two evolutionary ages. Moreover, proteins in protein complexes and topological modules show significantly low evolutionary rates than those not in these modules. Our results suggest a hypothesis of modularity in the evolution of yeast protein interaction network as systems evolution. PMID:25914446

  14. The Semantics of the Modular Architecture of Protein Structures.

    PubMed

    Hleap, Jose Sergio; Blouin, Christian

    2016-01-01

    Protein structures can be conceptualized as context-aware self-organizing systems. One of its emerging properties is a modular architecture. Such modular architecture has been identified as domains and defined as its units of evolution and function. However, this modular architecture is not exclusively defined by domains. Also, the definition of a domain is an ongoing debate. Here we propose differentiating structural, evolutionary and functional domains as distinct concepts. Defining domains or modules is confounded by diverse definitions of the concept, and also by other elements inherent to protein structures. An apparent hierarchy in protein structure architecture is one of these elements, where lower level interactions may create noise for the definition of higher levels. Diverse modularity-molding factors such as folding, function, and selection, can have a misleading effect when trying to define a given type of module. It is thus important to keep in mind this complexity when defining modularity in protein structures and interpreting the outcome modularity inference approaches. PMID:26412786

  15. Benchmark data for identifying multi-functional types of membrane proteins.

    PubMed

    Wan, Shibiao; Mak, Man-Wai; Kung, Sun-Yuan

    2016-09-01

    Identifying membrane proteins and their multi-functional types is an indispensable yet challenging topic in proteomics and bioinformatics. In this article, we provide data that are used for training and testing Mem-ADSVM (Wan et al., 2016. "Mem-ADSVM: a two-layer multi-label predictor for identifying multi-functional types of membrane proteins" [1]), a two-layer multi-label predictor for predicting multi-functional types of membrane proteins. PMID:27294176

  16. Multifunctional clickable and protein-repellent magnetic silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Estupiñán, Diego; Bannwarth, Markus B.; Mylon, Steven E.; Landfester, Katharina; Muñoz-Espí, Rafael; Crespy, Daniel

    2016-01-01

    Silica nanoparticles are versatile materials whose physicochemical surface properties can be precisely adjusted. Because it is possible to combine several functionalities in a single carrier, silica-based materials are excellent candidates for biomedical applications. However, the functionality of the nanoparticles can get lost upon exposure to biological media due to uncontrolled biomolecule adsorption. Therefore, it is important to develop strategies that reduce non-specific protein-particle interactions without losing the introduced surface functionality. Herein, organosilane chemistry is employed to produce magnetic silica nanoparticles bearing differing amounts of amino and alkene functional groups on their surface as orthogonally addressable chemical functionalities. Simultaneously, a short-chain zwitterion is added to decrease the non-specific adsorption of biomolecules on the nanoparticles surface. The multifunctional particles display reduced protein adsorption after incubation in undiluted fetal bovine serum as well as in single protein solutions (serum albumin and lysozyme). Besides, the particles retain their capacity to selectively react with biomolecules. Thus, they can be covalently bio-functionalized with an antibody by means of orthogonal click reactions. These features make the described multifunctional silica nanoparticles a promising system for the study of surface interactions with biomolecules, targeting, and bio-sensing.Silica nanoparticles are versatile materials whose physicochemical surface properties can be precisely adjusted. Because it is possible to combine several functionalities in a single carrier, silica-based materials are excellent candidates for biomedical applications. However, the functionality of the nanoparticles can get lost upon exposure to biological media due to uncontrolled biomolecule adsorption. Therefore, it is important to develop strategies that reduce non-specific protein-particle interactions without losing the

  17. Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages

    PubMed Central

    del Sol, Antonio; Araúzo-Bravo, Marcos J; Amoros, Dolors; Nussinov, Ruth

    2007-01-01

    Background Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. Results We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Gαs subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization. Conclusion Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages. PMID:17531094

  18. Self-healing supramolecular bioelastomers with shape memory property as a multifunctional platform for biomedical applications via modular assembly.

    PubMed

    Wu, Yaobin; Wang, Ling; Zhao, Xin; Hou, Sen; Guo, Baolin; Ma, Peter X

    2016-10-01

    Mimicking native functional dynamics for traditional biomaterials such as thermoset elastomers is limited due to their lack of responsiveness to biological stimuli and difficulties to incorporate biofunctionalities. Furthermore, the mechanical fracture of traditional thermoset elastomers caused by irreversible covalent bond rupture would lead to their permanent loss of properties. To overcome these challenges, degradable self-healed supramolecular bioelastomers are designed by an elastic poly(glycerol sebacate) (PGS) backbone and multiple hydrogen-bonding ureido-pyrimidinone (UPy) grafts. These supramolecular elastic polymers exhibit efficient self-healing, rapid shape-memory abilities and highly tunable mechanical properties due to the dynamic supramolecular interactions, and perform a good biocompatibility in vitro and a mild host response in vivo. By combining modular approaches, these supramolecular bioelastomers have been further assembled into a multifunctional platform to expand their applications in different biomedical fields. These include a complex 3D scaffold with shape-memory capacity and anisotropic mechanical properties, a controllable drug delivery model via a layer-by-layer technique, a surface antibacterial composite by physical modification, and a spatial oriented cell co-culture system via incorporating different cell-laden self-healing films, demonstrating their potential as building blocks in a wide range of biomedical applications where dynamic properties and biological functions are desired. PMID:27424213

  19. Modular microfluidics for point-of-care protein purifications.

    PubMed

    Millet, L J; Lucheon, J D; Standaert, R F; Retterer, S T; Doktycz, M J

    2015-04-21

    Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules. PMID:25740172

  20. Modular microfluidics for point-of-care protein purifications

    SciTech Connect

    Millet, L. J.; Lucheon, J. D.; Standaert, R. F.; Retterer, S. T.; Doktycz, M. J.

    2015-01-01

    Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. In conclusion, we demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.

  1. Biomimetic surface coatings from modular amphiphilic proteins

    NASA Astrophysics Data System (ADS)

    Harden, James; Wan, Fan; Fischer, Stephen; Dick, Scott

    2010-03-01

    Recombinant DNA methods have been used to develop a library of diblock protein polymers for creating designer biofunctional interfaces. These proteins are composed of a surface-active, amphiphilic block joined to a disordered, water soluble block with an end terminal bioactive domain. The amphiphilic block has a strong affinity for many synthetic polymer surfaces, providing a facile means of imparting biological functionality to otherwise bio-neutral materials through physical self-assembly. We have incorporated a series of bioactive end domains into this diblock motif, including sequences that encode specific cell binding and signaling functions of extracellular matrix constituents (e.g. RGD and YIGSR). In this talk, we show that these diblock constructs self-assemble into biofunctional surface coatings on several model synthetic polymer materials. We demonstrate that surface adsorption of the proteins has minimal impacts on the presentation of the bioactive domains in the soluble block, and through the use of microscopic and cell proliferation assays, we show that the resulting biofunctional interfaces are capable of inducing appropriate cellular responses in a variety of human cell types.

  2. Protein disulfide isomerase a multifunctional protein with multiple physiological roles

    NASA Astrophysics Data System (ADS)

    Ali Khan, Hyder; Mutus, Bulent

    2014-08-01

    Protein disulfide isomerase (PDI), is a member of the thioredoxin superfamily of redox proteins. PDI has three catalytic activities including, thiol-disulfide oxireductase, disulfide isomerase and redox-dependent chaperone. Originally, PDI was identified in the lumen of the endoplasmic reticulum and subsequently detected at additional locations, such as cell surfaces and the cytosol. This review will provide an overview of the recent advances in relating the structural features of PDI to its multiple catalytic roles as well as its physiological and pathophysiological functions related to redox regulation and protein folding.

  3. Protein-assisted self-assembly of multifunctional nanoparticles

    PubMed Central

    Nikitin, Maxim P.; Zdobnova, Tatiana A.; Lukash, Sergey V.; Stremovskiy, Oleg A.; Deyev, Sergey M.

    2010-01-01

    A bioengineering method for self-assembly of multifunctional superstructures with in-advance programmable properties has been proposed. The method employs two unique proteins, barnase and barstar, to rapidly join the structural components together directly in water solutions. The properties of the superstructures can be designed on demand by linking different agents of various sizes and chemical nature, designated for specific goals. As a proof of concept, colloidally stable trifunctional structures have been assembled by binding together magnetic particles, quantum dots, and antibodies using barnase and barstar. The assembly has demonstrated that the bonds between these proteins are strong enough to hold macroscopic (5 nm–3 μm) particles together. Specific interaction of such superstructures with cancer cells resulted in fluorescent labeling of the cells and their responsiveness to magnetic field. The method can be used to join inorganic moieties, organic particles, and single biomolecules for synergistic use in different applications such as biosensors, photonics, and nanomedicine. PMID:20231484

  4. Triple gene block: modular design of a multifunctional machine for plant virus movement.

    PubMed

    Morozov, Sergey Yu; Solovyev, Andrey G

    2003-06-01

    Many plant virus genera encode a 'triple gene block' (TGB), a specialized evolutionarily conserved gene module involved in the cell-to-cell and long-distance movement of viruses. The TGB-based transport system exploits the co-ordinated action of three polypeptides to deliver viral genomes to plasmodesmata and to accomplish virus entry into neighbouring cells. Although data obtained on both the TGB and well-studied single protein transport systems clearly demonstrate that plant viruses employ host cell pathways for intra- and intercellular trafficking of genomic nucleic acids and proteins, there is no integral picture of the details of molecular events during TGB-mediated virus movement. Undoubtedly, understanding the molecular basis of the concerted action of TGB-encoded proteins in transporting viral genomes from cell to cell should provide new insights into the general principles of movement protein function. This review describes the structure, phylogeny and expression of TGB proteins, their roles in virus cell-to-cell movement and potential influence on host antiviral defences. PMID:12771402

  5. Modular microfluidics for point-of-care protein purifications

    DOE PAGESBeta

    Millet, L. J.; Lucheon, J. D.; Standaert, R. F.; Retterer, S. T.; Doktycz, M. J.

    2015-01-01

    Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured tomore » suit a variety of fluidic operations or biochemical processes. In conclusion, we demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.« less

  6. The generation of zinc finger proteins by modular assembly

    PubMed Central

    Bhakta, Mital; Segal, David J.

    2015-01-01

    The modular assembly (MA) method of generating engineered zinc finger proteins (ZFPs) was the first practical method for creating custom DNA-binding proteins. As such, MA has enabled a vast exploration of sequence-specific methods and reagents, ushering in the modern era of zinc finger-based applications that are described in this volume. The first zinc finger nuclease to cleave an endogenous site was created using MA, as was the first artificial transcription factor to enter phase II clinical trials. In recent years, other excellent methods have been developed that improved the affinity and specificity of the engineered ZFPs. However, MA is still used widely for many applications. This chapter will describe methods and give guidance for the creation of ZFPs using MA. Such ZFPs might be useful as starting materials to perform other methods described in this volume. Here, we also describe a single-strand annealing recombination assay for the initial testing of zinc finger nucleases. PMID:20680825

  7. Split green fluorescent protein as a modular binding partner for protein crystallization

    SciTech Connect

    Nguyen, Hau B.; Hung, Li-Wei; Yeates, Todd O.; Terwilliger, Thomas C. Waldo, Geoffrey S.

    2013-12-01

    A strategy using a new split green fluorescent protein (GFP) as a modular binding partner to form stable protein complexes with a target protein is presented. The modular split GFP may open the way to rapidly creating crystallization variants. A modular strategy for protein crystallization using split green fluorescent protein (GFP) as a crystallization partner is demonstrated. Insertion of a hairpin containing GFP β-strands 10 and 11 into a surface loop of a target protein provides two chain crossings between the target and the reconstituted GFP compared with the single connection afforded by terminal GFP fusions. This strategy was tested by inserting this hairpin into a loop of another fluorescent protein, sfCherry. The crystal structure of the sfCherry-GFP(10–11) hairpin in complex with GFP(1–9) was determined at a resolution of 2.6 Å. Analysis of the complex shows that the reconstituted GFP is attached to the target protein (sfCherry) in a structurally ordered way. This work opens the way to rapidly creating crystallization variants by reconstituting a target protein bearing the GFP(10–11) hairpin with a variety of GFP(1–9) mutants engineered for favorable crystallization.

  8. Modular synthetic inverters from zinc finger proteins and small RNAs

    DOE PAGESBeta

    Hsia, Justin; Holtz, William J.; Maharbiz, Michel M.; Arcak, Murat; Keasling, Jay D.; Rao, Christopher V.

    2016-02-17

    Synthetic zinc finger proteins (ZFPs) can be created to target promoter DNA sequences, repressing transcription. The binding of small RNA (sRNA) to ZFP mRNA creates an ultrasensitive response to generate higher effective Hill coefficients. Here we combined three “off the shelf” ZFPs and three sRNAs to create new modular inverters in E. coli and quantify their behavior using induction fold. We found a general ordering of the effects of the ZFPs and sRNAs on induction fold that mostly held true when combining these parts. We then attempted to construct a ring oscillator using our new inverters. In conclusion, our chosenmore » parts performed insufficiently to create oscillations, but we include future directions for improvement upon our work presented here.« less

  9. Modular Synthetic Inverters from Zinc Finger Proteins and Small RNAs

    PubMed Central

    Hsia, Justin; Holtz, William J.; Maharbiz, Michel M.; Arcak, Murat; Keasling, Jay D.

    2016-01-01

    Synthetic zinc finger proteins (ZFPs) can be created to target promoter DNA sequences, repressing transcription. The binding of small RNA (sRNA) to ZFP mRNA creates an ultrasensitive response to generate higher effective Hill coefficients. Here we combined three “off the shelf” ZFPs and three sRNAs to create new modular inverters in E. coli and quantify their behavior using induction fold. We found a general ordering of the effects of the ZFPs and sRNAs on induction fold that mostly held true when combining these parts. We then attempted to construct a ring oscillator using our new inverters. Our chosen parts performed insufficiently to create oscillations, but we include future directions for improvement upon our work presented here. PMID:26886888

  10. Modularity of a carbon-fixing protein organelle

    PubMed Central

    Bonacci, Walter; Teng, Poh K.; Afonso, Bruno; Niederholtmeyer, Henrike; Grob, Patricia; Silver, Pamela A.; Savage, David F.

    2012-01-01

    Bacterial microcompartments are proteinaceous complexes that catalyze metabolic pathways in a manner reminiscent of organelles. Although microcompartment structure is well understood, much less is known about their assembly and function in vivo. We show here that carboxysomes, CO2-fixing microcompartments encoded by 10 genes, can be heterologously produced in Escherichia coli. Expression of carboxysomes in E. coli resulted in the production of icosahedral complexes similar to those from the native host. In vivo, the complexes were capable of both assembling with carboxysomal proteins and fixing CO2. Characterization of purified synthetic carboxysomes indicated that they were well formed in structure, contained the expected molecular components, and were capable of fixing CO2 in vitro. In addition, we verify association of the postulated pore-forming protein CsoS1D with the carboxysome and show how it may modulate function. We have developed a genetic system capable of producing modular carbon-fixing microcompartments in a heterologous host. In doing so, we lay the groundwork for understanding these elaborate protein complexes and for the synthetic biological engineering of self-assembling molecular structures. PMID:22184212

  11. Modularity of a carbon-fixing protein organelle.

    PubMed

    Bonacci, Walter; Teng, Poh K; Afonso, Bruno; Niederholtmeyer, Henrike; Grob, Patricia; Silver, Pamela A; Savage, David F

    2012-01-10

    Bacterial microcompartments are proteinaceous complexes that catalyze metabolic pathways in a manner reminiscent of organelles. Although microcompartment structure is well understood, much less is known about their assembly and function in vivo. We show here that carboxysomes, CO(2)-fixing microcompartments encoded by 10 genes, can be heterologously produced in Escherichia coli. Expression of carboxysomes in E. coli resulted in the production of icosahedral complexes similar to those from the native host. In vivo, the complexes were capable of both assembling with carboxysomal proteins and fixing CO(2). Characterization of purified synthetic carboxysomes indicated that they were well formed in structure, contained the expected molecular components, and were capable of fixing CO(2) in vitro. In addition, we verify association of the postulated pore-forming protein CsoS1D with the carboxysome and show how it may modulate function. We have developed a genetic system capable of producing modular carbon-fixing microcompartments in a heterologous host. In doing so, we lay the groundwork for understanding these elaborate protein complexes and for the synthetic biological engineering of self-assembling molecular structures. PMID:22184212

  12. An integrated approach to identify protein complex based on best neighbour and modularity increment.

    PubMed

    Shen, Xianjun; Zhao, Yanli; Li, Yanan; Yi, Yang; He, Tingting; Yang, Jincai

    2015-01-01

    In order to overcome the limitations of global modularity and the deficiency of local modularity, we propose a hybrid modularity measure Local-Global Quantification (LGQ) which considers global modularity and local modularity together. LGQ adopts a suitable module feature adjustable parameter to control the balance of global detecting capability and local search capability in Protein-Protein Interactions (PPI) Network. Furthermore, we develop a new protein complex mining algorithm called Best Neighbour and Local-Global Quantification (BN-LGQ) which integrates the best neighbour node and modularity increment. BN-LGQ expands the protein complex by fast searching the best neighbour node of the current cluster and by calculating the modularity increment as a metric to determine whether the best neighbour node can join the current cluster. The experimental results show BN-LGQ performs a better accuracy on predicting protein complexes and has a higher match with the reference protein complexes than MCL and MCODE algorithms. Moreover, BN-LGQ can effectively discover protein complexes with better biological significance in the PPI network. PMID:26336669

  13. Protein cofactor competition regulates the action of a multifunctional RNA helicase in different pathways

    PubMed Central

    Heininger, Annika U.; Hackert, Philipp; Andreou, Alexandra Z.; Boon, Kum-Loong; Memet, Indira; Prior, Mira; Clancy, Anne; Schmidt, Bernhard; Urlaub, Henning; Schleiff, Enrico; Sloan, Katherine E.; Deckers, Markus; Lührmann, Reinhard; Enderlein, Jörg; Klostermeier, Dagmar; Rehling, Peter; Bohnsack, Markus T.

    2016-01-01

    ABSTRACT A rapidly increasing number of RNA helicases are implicated in several distinct cellular processes, however, the modes of regulation of multifunctional RNA helicases and their recruitment to different target complexes have remained unknown. Here, we show that the distribution of the multifunctional DEAH-box RNA helicase Prp43 between its diverse cellular functions can be regulated by the interplay of its G-patch protein cofactors. We identify the orphan G-patch protein Cmg1 (YLR271W) as a novel cofactor of Prp43 and show that it stimulates the RNA binding and ATPase activity of the helicase. Interestingly, Cmg1 localizes to the cytoplasm and to the intermembrane space of mitochondria and its overexpression promotes apoptosis. Furthermore, our data reveal that different G-patch protein cofactors compete for interaction with Prp43. Changes in the expression levels of Prp43-interacting G-patch proteins modulate the cellular localization of Prp43 and G-patch protein overexpression causes accumulation of the helicase in the cytoplasm or nucleoplasm. Overexpression of several G-patch proteins also leads to defects in ribosome biogenesis that are consistent with withdrawal of the helicase from this pathway. Together, these findings suggest that the availability of cofactors and the sequestering of the helicase are means to regulate the activity of multifunctional RNA helicases and their distribution between different cellular processes. PMID:26821976

  14. Protein cofactor competition regulates the action of a multifunctional RNA helicase in different pathways.

    PubMed

    Heininger, Annika U; Hackert, Philipp; Andreou, Alexandra Z; Boon, Kum-Loong; Memet, Indira; Prior, Mira; Clancy, Anne; Schmidt, Bernhard; Urlaub, Henning; Schleiff, Enrico; Sloan, Katherine E; Deckers, Markus; Lührmann, Reinhard; Enderlein, Jörg; Klostermeier, Dagmar; Rehling, Peter; Bohnsack, Markus T

    2016-01-01

    A rapidly increasing number of RNA helicases are implicated in several distinct cellular processes, however, the modes of regulation of multifunctional RNA helicases and their recruitment to different target complexes have remained unknown. Here, we show that the distribution of the multifunctional DEAH-box RNA helicase Prp43 between its diverse cellular functions can be regulated by the interplay of its G-patch protein cofactors. We identify the orphan G-patch protein Cmg1 (YLR271W) as a novel cofactor of Prp43 and show that it stimulates the RNA binding and ATPase activity of the helicase. Interestingly, Cmg1 localizes to the cytoplasm and to the intermembrane space of mitochondria and its overexpression promotes apoptosis. Furthermore, our data reveal that different G-patch protein cofactors compete for interaction with Prp43. Changes in the expression levels of Prp43-interacting G-patch proteins modulate the cellular localization of Prp43 and G-patch protein overexpression causes accumulation of the helicase in the cytoplasm or nucleoplasm. Overexpression of several G-patch proteins also leads to defects in ribosome biogenesis that are consistent with withdrawal of the helicase from this pathway. Together, these findings suggest that the availability of cofactors and the sequestering of the helicase are means to regulate the activity of multifunctional RNA helicases and their distribution between different cellular processes. PMID:26821976

  15. A Modular Approach for Assembling Aldehyde-Tagged Proteins on DNA Scaffolds

    PubMed Central

    2015-01-01

    Expansion of antibody scaffold diversity has the potential to expand the neutralizing capacity of the immune system and to generate enhanced therapeutics and probes. Systematic exploration of scaffold diversity could be facilitated with a modular and chemical scaffold for assembling proteins, such as DNA. However, such efforts require simple, modular, and site-specific methods for coupling antibody fragments or bioactive proteins to nucleic acids. To address this need, we report a modular approach for conjugating synthetic oligonucleotides to proteins with aldehyde tags at either terminus or internal loops. The resulting conjugates are assembled onto DNA-based scaffolds with low nanometer spatial resolution and can bind to live cells. Thus, this modular and site-specific conjugation strategy provides a new tool for exploring the potential of expanded scaffold diversity in immunoglobulin-based probes and therapeutics. PMID:25029632

  16. Modular protein supplements and their application to long-term care.

    PubMed

    Castellanos, Victoria Hammer; Litchford, Mary D; Campbell, Wayne W

    2006-10-01

    Modular protein supplements are added to either the diet or enteral formula to increase the protein or amino acid intakes of people who are nutritionally compromised. Protein supplements are aggressively marketed to long-term care clinicians because protein energy malnutrition and wounds are a common problem in this care setting. It can be challenging for clinicians to distinguish one product from another and to determine the best product for a specific application or nutrition care goal. Modular protein products can be sorted into 4 categories: (1) protein concentrates derived from a complete protein such as milk, soy, or eggs; (2) protein concentrates derived from collagen, either alone or in combination with a complete protein; (3) doses of 1 or more dispensable (nonessential) amino acids; and (4) hybrids of the complete or collagen-based proteins and amino acid dose. Modular protein supplements are generally provided either as a substrate for protein synthesis or as a source of 1 or more amino acids that may be conditionally indispensable (conditionally essential) under certain disease conditions. This review provides guidelines for the use of modular protein supplements according to their intended physiologic function and the assessment and nutrition care goals of the long-term care resident. PMID:16998147

  17. Multifunctional nanoreactor for comprehensive characterization of membrane proteins based on surface functionalized mesoporous foams.

    PubMed

    Fang, Xiaoni; Qiao, Liang; Yan, Guoquan; Yang, Pengyuan; Liu, Baohong

    2015-09-15

    An integrated protocol is proposed here for efficient analysis of membrane proteins based on surface functionalized mesoporous graphene foams (MGF). The inherent hydrophobic nature of MGF and surface modification with hydrophilic chitosan (CS) make it highly suitable for the enrichment of hydrophobic membrane proteins from organic solvent, while remaining well-dispersed in aqueous solution for subsequent proteolysis. Therefore, such a multifunctional reactor ensures a facile solvent adjustment route. Furthermore, as a chitosan modified nanoporous reactor, it also provides a biocompatible nanoenvironment that can maintain the stability and activity of enzymes to realize efficient in situ digestion of the enriched membrane proteins. The concept was first proved with a standard hydrophobic membrane protein, bacteriorhodopsin, where a high number of identified peptides and amino acid sequence coverage were achieved even at extremely low protein concentration. The mesoporous reaction system was further applied to the analysis of complex real-case proteome samples, where 931 membrane proteins were identified in triplicate analyses by 2D LC-MS/MS. In contrast, with in-solution proteolysis, only 73 membrane proteins were identified from the same sample by the same 2D LC-MS/MS. The identified membrane proteins by the MGF-CS protocol include many biomarkers of the cell line. These results suggest that the multifunctional MGF-CS protocol is of great value to facilitate the comprehensive characterization of membrane proteins in the proteome research. PMID:26305297

  18. Soy-Protein-Based Nanofabrics for Highly Efficient and Multifunctional Air Filtration.

    PubMed

    Souzandeh, Hamid; Johnson, Kyle S; Wang, Yu; Bhamidipaty, Keshava; Zhong, Wei-Hong

    2016-08-10

    Proteins are well-known by their numerous active functional groups along the polypeptide chain. The variety of functional groups of proteins provides a great potential for proteins to interact with airborne pollutants with varying surface properties. However, to our knowledge, a successful demonstration of this potential has not been reported before. In this work, soy protein, a type of abundant plant protein, has been employed for the first time to fabricate multifunctional air-filtration materials. To take advantage of the functional groups of soy protein for air filtration, the soy protein was first well denatured to unfold the polypeptide chains and then fabricated into nanofibers with the help of poly(vinyl alcohol). It was found that the resultant nanofabrics showed high filtration efficiency not only for airborne particulates with a broad range of size but also for various toxic gaseous chemicals (e.g., formaldehyde and carbon monoxide), a capability that has not been realized by conventional air-filtering materials. This study indicates that protein-based nanofabrics are promising nanomaterials for multifunctional air-filtration applications. PMID:27439677

  19. Cinnamomin: a multifunctional type II ribosome-inactivating protein.

    PubMed

    He, Wen-Jun; Liu, Wang-Yi

    2003-07-01

    Plant ribosome-inactivating proteins (RIPs) are a group of toxic proteins that can irreversibly inactivate ribosomes by specifically removing the conserved adenine base from the "Sarcin/Ricin domain" of the 28S RNA in ribosome. Cinnamomin is a novel type II RIP isolated in our laboratory from the mature seeds of camphor tree. Besides site-specific deadenylation of the A4324 in the Sarcin/Ricin domain of rat ribosome, this protein could also release the adenine base from DNA molecules at multiple sites and from AMP, ADP, dAMP and adenosine. Furthermore, cinnamomin displays cytotoxicity to carcinoma cells and insect larvae by modifying their ribosomal RNA. These functions possessed by cinnamomin shed a new light on the possible application of cinnamomin in the field of immunotoxin design and transgenic reagents. In this review, we introduce the major recent results on cinnamomin obtained in our laboratory, including purification of this protein, characterization of its enzymatic mechanism, structure and function, gene pattern, physiological role and its biological implications in cytotoxicity. PMID:12672471

  20. [DREAM/Calsenilin/KChIP3: a new multifunctional protein in nervous system].

    PubMed

    Zhang, Ying; Wang, Yun

    2005-07-01

    A newly found transcription factor-DREAM can bind specifically with downstream regulatory element of genes, such as PPD, Hrk and c-Fos, and repress gene expression. It represents the first known Ca2+ binding protein to function as a DNA-binding transcription regulator. This provides a new mechanism of Ca2+ dependent regulation of gene expression in addition to protein kinase/phosphatase signaling pathway. In fact, DREAM, calsenilin and KChIP3, which are identified by different laboratories, are the same protein. So DREAM is a multifunctional protein, including PS interacting protein, Kv4 regulatory protein and transcription factor. The distribution, function and regulation of DREAM, as well as relationship between DREAM and pain, are reviewed in the present article. PMID:16270816

  1. ThermoTRP channels as modular proteins with allosteric gating.

    PubMed

    Latorre, Ramon; Brauchi, Sebastian; Orta, Gerardo; Zaelzer, Cristián; Vargas, Guillermo

    2007-01-01

    . Caspani, P.A. Heppenstall, Direct activation of the ion channel TRPA1 by Ca(2+), Nat. Neurosci. 10 (2007) 277-279]. These stimuli include voltage, pH, agonist binding, and temperature. Understanding how each of these distinct physiological signals regulate channel opening will be informative about the mechanical linkages that can act either independently or in concert to influence channel activation. In this paper we show that thermoTRP channel-forming proteins are modular in the sense that certain structure or structures (modules) confer temperature-dependent regulation, whereas others confer voltage-dependent regulation. We also discuss the thermodynamic basis of heat and cold activation in an effort to elucidate what confer to these channels the capability to be gated by temperature directly. PMID:17499848

  2. Quantification and functional analysis of modular protein evolution in a dense phylogenetic tree.

    PubMed

    Moore, Andrew D; Grath, Sonja; Schüler, Andreas; Huylmans, Ann K; Bornberg-Bauer, Erich

    2013-05-01

    Modularity is a hallmark of molecular evolution. Whether considering gene regulation, the components of metabolic pathways or signaling cascades, the ability to reuse autonomous modules in different molecular contexts can expedite evolutionary innovation. Similarly, protein domains are the modules of proteins, and modular domain rearrangements can create diversity with seemingly few operations in turn allowing for swift changes to an organism's functional repertoire. Here, we assess the patterns and functional effects of modular rearrangements at high resolution. Using a well resolved and diverse group of pancrustaceans, we illustrate arrangement diversity within closely related organisms, estimate arrangement turnover frequency and establish, for the first time, branch-specific rate estimates for fusion, fission, domain addition and terminal loss. Our results show that roughly 16 new arrangements arise per million years and that between 64% and 81% of these can be explained by simple, single-step modular rearrangement events. We find evidence that the frequencies of fission and terminal deletion events increase over time, and that modular rearrangements impact all levels of the cellular signaling apparatus and thus may have strong adaptive potential. Novel arrangements that cannot be explained by simple modular rearrangements contain a significant amount of repeat domains that occur in complex patterns which we term "supra-repeats". Furthermore, these arrangements are significantly longer than those with a single-step rearrangement solution, suggesting that such arrangements may result from multi-step events. In summary, our analysis provides an integrated view and initial quantification of the patterns and functional impact of modular protein evolution in a well resolved phylogenetic tree. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly. PMID:23376183

  3. Human pyruvate kinase M2: a multifunctional protein.

    PubMed

    Gupta, Vibhor; Bamezai, Rameshwar N K

    2010-11-01

    Glycolysis, a central metabolic pathway, harbors evolutionary conserved enzymes that modulate and potentially shift the cellular metabolism on requirement. Pyruvate kinase, which catalyzes the last but rate-limiting step of glycolysis, is expressed in four isozymic forms, depending on the tissue requirement. M2 isoform (PKM2) is exclusively expressed in embryonic and adult dividing/tumor cells. This tetrameric allosterically regulated isoform is intrinsically designed to downregulate its activity by subunit dissociation (into dimer), which results in partial inhibition of glycolysis at the last step. This accumulates all upstream glycolytic intermediates as an anabolic feed for synthesis of lipids and nucleic acids, whereas reassociation of PKM2 into active tetramer replenishes the normal catabolism as a feedback after cell division. In addition, involvement of this enzyme in a variety of pathways, protein-protein interactions, and nuclear transport suggests its potential to perform multiple nonglycolytic functions with diverse implications, although multidimensional role of this protein is as yet not fully explored. This review aims to provide an overview of the involvement of PKM2 in various physiological pathways with possible functional implications. PMID:20857498

  4. E2 protein cage as a multifunctional nanoplatform

    NASA Astrophysics Data System (ADS)

    Dalmau Mallorqui, Merce

    Caged protein systems such as viral capsids, heat shock proteins, and ferritin are spherical structures that occur naturally in living organisms and are a growing class of biomimetic templates used to create new materials in nanotechnology. Such systems have been proposed as general drug carriers since they form highly symmetric nanoscale architectures that offer the potential to be tailored according to the desired application. Within this framework, this dissertation focuses on the design and development of a new drug delivery nanoplatform based on the E2 subunit of the pyruvate dehydrogenase protein from Bacillus stearothermophilus. This scaffold forms a 25-nm nanocapsule structure with a hollow cavity. We produced a variant of this protein consisting only of the structural core, and found the thermostability of this self-assembled scaffold to be unusually high, with an onset unfolding temperature of 81.1 +/- 0.9°C and an apparent midpoint unfolding temperature of 91.4 +/- 1.4°C. To evaluate the potential of this scaffold for encapsulation of guest molecules in the internal cavity, we made variants which altered the physicochemical properties of the hollow internal surface. These mutants, yielding up to 240 mutations within this cavity, assembled into correct architectures and exhibited high thermostability that was also comparable to the wild-type scaffold. To show the applicability of this scaffold we coupled two drug-like small molecules to the internal cavity. We also developed a new strategy for encapsulation of small hydrophobic drug molecules. This method is based on hydrophobic differences between the interior cavity and the external buffer to nucleate drug-like agents inside the protein cage. We demonstrate that internal mutations can introduce non-native functionality and enable molecular encapsulation within the cavity while still retaining the dodecahedral structure. Another surface amenable to modifications is the interface between subunits. Such

  5. The Legionella pneumophila Chaperonin - An Unusual Multifunctional Protein in Unusual Locations.

    PubMed

    Garduño, Rafael A; Chong, Audrey; Nasrallah, Gheyath K; Allan, David S

    2011-01-01

    The Legionella pneumophila chaperonin, high temperature protein B (HtpB), was discovered as a highly immunogenic antigen, only a few years after the identification of L. pneumophila as the causative agent of Legionnaires' disease. As its counterparts in other bacterial pathogens, HtpB did not initially receive further attention, particularly because research was focused on a few model chaperonins that were used to demonstrate that chaperonins are essential stress proteins, present in all cellular forms of life and involved in helping other proteins to fold. However, chaperonins have recently attracted increasing interest, particularly after several reports confirmed their multifunctional nature and the presence of multiple chaperonin genes in numerous bacterial species. It is now accepted that bacterial chaperonins are capable of playing a variety of protein folding-independent roles. HtpB is clearly a multifunctional chaperonin that according to its location in the bacterial cell, or in the L. pneumophila-infected cell, plays different roles. HtpB exposed on the bacterial cell surface can act as an invasion factor for non-phagocytic cells, whereas the HtpB released in the host cell can act as an effector capable of altering organelle trafficking, the organization of actin microfilaments and cell signaling pathways. The road to discover the multifunctional nature of HtpB has been exciting and here we provide a historical perspective of the key findings linked to such discovery, as well as a summary of the experimental work (old and new) performed in our laboratory. Our current understanding has led us to propose that HtpB is an ancient protein that L. pneumophila uses as a key molecular tool important to the intracellular establishment of this fascinating pathogen. PMID:21713066

  6. Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases

    PubMed Central

    Ishida, A; Sueyoshi, N; Shigeri, Y; Kameshita, I

    2008-01-01

    Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) play pivotal roles in intracellular Ca2+ signaling pathways. There is growing evidence that CaMKs are involved in the pathogenic mechanisms underlying various human diseases. In this review, we begin by briefly summarizing our knowledge of the involvement of CaMKs in the pathogenesis of various diseases suggested to be caused by the dysfunction/dysregulation or aberrant expression of CaMKs. It is widely known that the activities of CaMKs are strictly regulated by protein phosphorylation/dephosphorylation of specific phosphorylation sites. Since phosphorylation status is balanced by protein kinases and protein phosphatases, the mechanism of dephosphorylation/deactivation of CaMKs, corresponding to their ‘switching off', is extremely important, as is the mechanism of phosphorylation/activation corresponding to their ‘switching on'. Therefore, we focus on the regulation of multifunctional CaMKs by protein phosphatases. We summarize the current understanding of negative regulation of CaMKs by protein phosphatases. We also discuss the biochemical properties and physiological significance of a protein phosphatase that we designated as Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP), and those of its homologue CaMKP-N. Pharmacological applications of CaMKP inhibitors are also discussed. These compounds may be useful not only for exploring the physiological functions of CaMKP/CaMKP-N, but also as novel chemotherapies for various diseases. PMID:18454172

  7. Emerging Multifunctional Roles of Claudin Tight Junction Proteins in Bone

    PubMed Central

    Alshbool, Fatima. Z.

    2014-01-01

    The imbalance between bone formation and resorption during bone remodeling has been documented to be a major factor in the pathogenesis of osteoporosis. Recent evidence suggests a significant role for the tight junction proteins, Claudins (Cldns), in the regulation of bone remodeling processes. In terms of function, whereas Cldns act “canonically” as key determinants of paracellular permeability, there is considerable recent evidence to suggest that Cldns also participate in cell signaling, ie, a “noncanonical function”. To this end, Cldns have been shown to regulate cell proliferation, differentiation, and gene expression in a variety of cell types. The present review will discuss Cldns' structure, their expression profile, regulation of expression, and their canonical and non- canonical functions in general with special emphasis on bone cells. In order to shed light on the noncanonical functions of Cldns in bone, we will highlight the role of Cldn-18 in regulating bone resorption and osteoclast differentiation. Collectively, we hope to provide a framework for guiding future research on understanding how Cldns modulate osteoblast and osteoclast function and overall bone homeostasis. Such studies should provide valuable insights into the pathogenesis of osteoporosis, and may highlight Cldns as novel targets for the diagnosis and therapeutic management of osteoporosis. PMID:24758302

  8. Multifunctional Electrospun Nanofibers Incorporated with an Anti-infection Drug and Immobilized with Proteins

    NASA Astrophysics Data System (ADS)

    Zhou, Shufei

    Electrospinning has been used to fabricate ultrafine fibers with sizes ranging from nano to micrometers. Nanofibers electrospun from biocompatible and biodegradable polymers have been extensively investigated for their potential applications in wound healing and tissue regeneration. These nanofiber materials can be modified to incorporate bioactive molecules, such as antibacterial agents that provide infection control, or functional proteins which promote cell proliferation and tissue reconstruction. Despite the numerous studies on the development and design of nanofibers for biomedical applications, there has been little research on multifunctional nanofibers that are incorporated with both antibacterial drug(s) and bioactive proteins. The objective of the current study is, therefore, to develop nanofibers that are functionalized by several bioactive molecules. In this study, electrospinning was utilized to fabricate nanofibers from biodegradable polymers PLLA (Poly-L-lactide) and the copolymer PLLA-PEG (Polyethylene glycol)-NH2.A water soluble antibiotic drug, Tetracycline Hydrochloride (TCH), was incorporated into the electrospun nanofibers via emulsion electrospinning. The TCH-loaded nanofibers were surface modified to produce functional groups that can be further conjugated with a model protein, Bovine Serum Albumin (BSA).Drug releasing profiles of the medicated nanofibers were monitored and their antimicrobial properties were evaluated. Proteins (BSAs) immobilized on the fiber surface were verified by ATR-FTIR. The number of immobilized BSAs was determined using a UV-Vis spectrophotometer. The results of the study suggested that this multifunctional nanofibrous material could be a promising material for wound dressing or scaffolds for tissue engineering.

  9. Differential regulation by a peroxisome proliferator of the different multifunctional proteins in guinea pig: cDNA cloning of the guinea pig D-specific multifunctional protein 2.

    PubMed Central

    Caira, F; Clémencet, M C; Cherkaoui-Malki, M; Dieuaide-Noubhani, M; Pacot, C; Van Veldhoven, P P; Latruffe, N

    1998-01-01

    After our previous report on the cloning of two cDNA species in guinea pig, both encoding the same hepatic 79 kDa multifunctional protein 1 (MFP-1) [Caira, Cherkaoui-Malki, Hoefler and Latruffe (1996) FEBS Lett. 378, 57-60], here we report the cloning of a cDNA encoding a second multifunctional peroxisomal protein (MFP-2) in guinea-pig liver. This 2356 nt cDNA encodes a protein of 735 residues (79.7 kDa) whose sequence shows 83% identity with rat MFP-2 [Dieuaide-Noubhani, Novikov, Baumgart, Vanhooren, Fransen, Goethals, Vandekerckhove, Van Veldhoven and Mannaerts (1996) Eur. J. Biochem. 240, 660-666]. In parallel, we studied the effect of ciprofibrate, a hypolipaemic agent also known as peroxisome proliferator in rodent, on the expression of MFP-1 and MFP-2 (2.6 kb) in rats and guinea pigs. By Northern blotting analysis we demonstrated that three MFP-1-related mRNA species are expressed in the guinea-pig liver. The expression of two of them (3.5 and 2.6 kb) is slightly increased by ciprofibrate, whereas the 3.0 kb MFP-1 mRNA is, unlike the rat one, strongly down-regulated in guinea pigs treated with ciprofibrate. In a similar way, the hepatic expression of the guinea-pig 2.6 kb MFP-2 mRNA is also down-regulated in guinea pigs treated with ciprofibrate. These results demonstrate (1) that in contrast with the unique 3.0 kb MFP-1 rat mRNA, at least three hepatic MFP-1-related mRNA species are co-expressed in guinea pig; and (2) that, opposed to the accepted idea of non-responsiveness of the guinea pig to ciprofibrate, this drug affects MFP-1 and MFP-2 gene expression in this species. Also, the mRNA species for acyl-CoA oxidase and thiolase, two other enzymes of the peroxisomal beta-oxidation pathway that are induced severalfold in responsive species are down-regulated in guinea pig. This paper is the first, to our knowledge, reporting the down-regulation of the expression of genes encoding enzymes involved in the peroxisomal beta-oxidation of fatty acids (MFP-1) and

  10. Receptor activity-modifying proteins; multifunctional G protein-coupled receptor accessory proteins.

    PubMed

    Hay, Debbie L; Walker, Christopher S; Gingell, Joseph J; Ladds, Graham; Reynolds, Christopher A; Poyner, David R

    2016-04-15

    Receptor activity-modifying proteins (RAMPs) are single pass membrane proteins initially identified by their ability to determine the pharmacology of the calcitonin receptor-like receptor (CLR), a family B G protein-coupled receptor (GPCR). It is now known that RAMPs can interact with a much wider range of GPCRs. This review considers recent developments on the structure of the complexes formed between the extracellular domains (ECDs) of CLR and RAMP1 or RAMP2 as these provide insights as to how the RAMPs direct ligand binding. The range of RAMP interactions is also considered; RAMPs can interact with numerous family B GPCRs as well as examples of family A and family C GPCRs. They influence receptor expression at the cell surface, trafficking, ligand binding and G protein coupling. The GPCR-RAMP interface offers opportunities for drug targeting, illustrated by examples of drugs developed for migraine. PMID:27068971

  11. Urea carboxylase and allophanate hydrolase are components of a multifunctional protein in yeast.

    PubMed

    Sumrada, R A; Cooper, T G

    1982-08-10

    Saccharomyces cerevisiae can use urea as sole nitrogen source by degrading it in two steps (urea carboxylase and allophanate hydrolase) to ammonia and carbon dioxide. We previously demonstrated that: 1) the enzymatic functions required for degradation are encoded in two tightly linked genetic loci and 2) pleiotropic mutations each resulting in the loss of both activities are found in both loci. These and other observations led to the hypothesis that urea degradation might be catalyzed by a multifunctional polypeptide. Waheed and Castric (1977) J. Biol. Chem. 252, 1628-1632), on the other hand, purified urea amidolyase from Candida utilis and reported it to be a tetramer composed of nonidentical 70- and 170-kilodalton subunits. To resolve the differing views of urea amidolyase structure, we purified the protein using rapid methods designed to avoid proteolytic cleavage. Application of these methods resulted in the isolation of a single, inducible and repressible, 204-kilodalton species. We observed no evidence for the existence of nonidentical subunits. A similar inducible, high molecular weight species was also detected in C. utilis. These biochemical results support our earlier hypothesis that urea degradation is carried out in yeast by an inducible and repressible protein composed of identical, multifunctional subunits. PMID:6124544

  12. Multifunctional Transmembrane Protein Ligands for Cell-Specific Targeting of Plasma Membrane-Derived Vesicles.

    PubMed

    Zhao, Chi; Busch, David J; Vershel, Connor P; Stachowiak, Jeanne C

    2016-07-01

    Liposomes and nanoparticles that bind selectively to cell-surface receptors can target specific populations of cells. However, chemical conjugation of ligands to these particles is difficult to control, frequently limiting ligand uniformity and complexity. In contrast, the surfaces of living cells are decorated with highly uniform populations of sophisticated transmembrane proteins. Toward harnessing cellular capabilities, here it is demonstrated that plasma membrane vesicles (PMVs) derived from donor cells can display engineered transmembrane protein ligands that precisely target cells on the basis of receptor expression. These multifunctional targeting proteins incorporate (i) a protein ligand, (ii) an intrinsically disordered protein spacer to make the ligand sterically accessible, and (iii) a fluorescent protein domain that enables quantification of the ligand density on the PMV surface. PMVs that display targeting proteins with affinity for the epidermal growth factor receptor (EGFR) bind at increasing concentrations to breast cancer cells that express increasing levels of EGFR. Further, as an example of the generality of this approach, PMVs expressing a single-domain antibody against green fluorescence protein (eGFP) bind to cells expressing eGFP-tagged receptors with a selectivity of ≈50:1. The results demonstrate the versatility of PMVs as cell targeting systems, suggesting diverse applications from drug delivery to tissue engineering. PMID:27294846

  13. WHERE MULTIFUNCTIONAL DNA REPAIR PROTEINS MEET: MAPPING THE INTERACTION DOMAINS BETWEEN XPG AND WRN

    SciTech Connect

    Rangaraj, K.; Cooper, P.K.; Trego, K.S.

    2009-01-01

    The rapid recognition and repair of DNA damage is essential for the maintenance of genomic integrity and cellular survival. Multiple complex and interconnected DNA damage responses exist within cells to preserve the human genome, and these repair pathways are carried out by a specifi c interplay of protein-protein interactions. Thus a failure in the coordination of these processes, perhaps brought about by a breakdown in any one multifunctional repair protein, can lead to genomic instability, developmental and immunological abnormalities, cancer and premature aging. This study demonstrates a novel interaction between two such repair proteins, Xeroderma pigmentosum group G protein (XPG) and Werner syndrome helicase (WRN), that are both highly pleiotropic and associated with inherited genetic disorders when mutated. XPG is a structure-specifi c endonuclease required for the repair of UV-damaged DNA by nucleotide excision repair (NER), and mutations in XPG result in the diseases Xeroderma pigmentosum (XP) and Cockayne syndrome (CS). A loss of XPG incision activity results in XP, whereas a loss of non-enzymatic function(s) of XPG causes CS. WRN is a multifunctional protein involved in double-strand break repair (DSBR), and consists of 3’–5’ DNA-dependent helicase, 3’–5’ exonuclease, and single-strand DNA annealing activities. Nonfunctional WRN protein leads to Werner syndrome, a premature aging disorder with increased cancer incidence. Far Western analysis was used to map the interacting domains between XPG and WRN by denaturing gel electrophoresis, which separated purifi ed full length and recombinant XPG and WRN deletion constructs, based primarily upon the length of each polypeptide. Specifi c interacting domains were visualized when probed with the secondary protein of interest which was then detected by traditional Western analysis using the antibody of the secondary protein. The interaction between XPG and WRN was mapped to the C-terminal region of

  14. Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein family.

    PubMed Central

    Chuang, T H; Xu, X; Kaartinen, V; Heisterkamp, N; Groffen, J; Bokoch, G M

    1995-01-01

    Philadelphia chromosome-positive leukemias result from the fusion of the BCR and ABL genes, which generates a functional chimeric molecule. The Abr protein is very similar to Bcr but lacks a structural domain which may influence its biological regulatory capabilities. Both Abr and Bcr have a GTPase-activating protein (GAP) domain similar to those found in other proteins that stimulate GTP hydrolysis by members of the Rho family of GTP-binding proteins, as well as a region of homology with the guanine nucleotide dissociation-stimulating domain of the DBL oncogene product. We purified as recombinant fusion proteins the GAP- and Dbl-homology domains of both Abr and Bcr. The Dbl-homology domains of Bcr and Abr were active in stimulating GTP binding to CDC42Hs, RhoA, Rac1, and Rac2 (rank order, CDC42Hs > RhoA > Rac1 = Rac2) but were inactive toward Rap1A and Ha-Ras. Both Bcr and Abr acted as GAPs for Rac1, Rac2, and CDC42Hs but were inactive toward RhoA, Rap1A, and Ha-Ras. Each individual domain bound in a noncompetitive manner to GTP-binding protein substrates. These data suggest the multifunctional Bcr and Abr proteins might interact simultaneously and/or sequentially with members of the Rho family to regulate and coordinate cellular signaling. Images Fig. 3 PMID:7479768

  15. Structure and Energetic Contributions of a Designed Modular Peptide-Binding Protein with Picomolar Affinity.

    PubMed

    Hansen, Simon; Tremmel, Dirk; Madhurantakam, Chaithanya; Reichen, Christian; Mittl, Peer R E; Plückthun, Andreas

    2016-03-16

    Natural armadillo repeat proteins (nArmRP) like importin-α or β-catenin bind their target peptides such that each repeat interacts with a dipeptide unit within the stretched target peptide. However, this modularity is imperfect and also restricted to short peptide stretches of usually four to six consecutive amino acids. Here we report the development and characterization of a regularized and truly modular peptide-specific binding protein, based on designed armadillo repeat proteins (dArmRP), binding to peptides of alternating lysine and arginine residues (KR)n. dArmRP were obtained from nArmRP through cycles of extensive protein engineering, which rendered them more uniform. This regularity is reflected in the consistent binding of dArmRP to (KR)-peptides, where affinities depend on the lengths of target peptides and the number of internal repeats in a very systematic manner, thus confirming the modularity of the interaction. This exponential dependency between affinity and recognition length suggests that each module adds a constant increment of binding energy to sequence-specific recognition. This relationship was confirmed by comprehensive mutagenesis studies that also reveal the importance of individual peptide side chains. The 1.83 Å resolution crystal structure of a dArmRP with five identical internal repeats in complex with the cognate (KR)5 peptide proves a modular binding mode, where each dipeptide is recognized by one internal repeat. The confirmation of this true modularity over longer peptide stretches lays the ground for the design of binders with different specificities and tailored affinities by the assembly of dipeptide-specific modules based on armadillo repeats. PMID:26878586

  16. Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents

    PubMed Central

    John, Renu; Nguyen, Freddy T.; Kolbeck, Kenneth J.; Chaney, Eric J.; Marjanovic, Marina; Suslick, Kenneth S.; Boppart, Stephen A.

    2012-01-01

    Purpose In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications. Procedures A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to αvβ3 integrin receptors that are over-expressed in tumors and atherosclerotic lesions. Results These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres. Conclusions Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance. PMID:21298354

  17. The peroxisomal multifunctional protein interacts with cortical microtubules in plant cells

    PubMed Central

    2005-01-01

    Background The plant peroxisomal multifunctional protein (MFP) possesses up to four enzymatic activities that are involved in catalyzing different reactions of fatty acid β-oxidation in the peroxisome matrix. In addition to these peroxisomal activities, in vitro assays revealed that rice MFP possesses microtubule- and RNA-binding activities suggesting that this protein also has important functions in the cytosol. Results We demonstrate that MFP is an authentic microtubule-binding protein, as it localized to the cortical microtubule array in vivo, in addition to its expected targeting to the peroxisome matrix. MFP does not, however, interact with the three mitotic microtubule arrays. Microtubule co-sedimentation assays of truncated versions of MFP revealed that multiple microtubule-binding domains are present on the MFP polypeptide. This indicates that these regions function together to achieve high-affinity binding of the full-length protein. Real-time imaging of a transiently expressed green fluorescent protein-MFP chimera in living plant cells illustrated that a dynamic, spatial interaction exits between peroxisomes and cortical microtubules as peroxisomes move along actin filaments or oscillate at fixed locations. Conclusion Plant MFP is associated with the cortical microtubule array, in addition to its expected localization in the peroxisome. This observation, coupled with apparent interactions that frequently occur between microtubules and peroxisomes in the cell cortex, supports the hypothesis that MFP is concentrated on microtubules in order to facilitate the regulated import of MFP into peroxisomes. PMID:16313672

  18. Mem-ADSVM: A two-layer multi-label predictor for identifying multi-functional types of membrane proteins.

    PubMed

    Wan, Shibiao; Mak, Man-Wai; Kung, Sun-Yuan

    2016-06-01

    Identifying membrane proteins and their multi-functional types is an indispensable yet challenging topic in proteomics and bioinformatics. However, most of the existing membrane-protein predictors have the following problems: (1) they do not predict whether a given protein is a membrane protein or not; (2) they are limited to predicting membrane proteins with single-label functional types but ignore those with multi-functional types; and (3) there is still much room for improvement for their performance. To address these problems, this paper proposes a two-layer multi-label predictor, namely Mem-ADSVM, which can identify membrane proteins (Layer I) and their multi-functional types (Layer II). Specifically, given a query protein, its associated gene ontology (GO) information is retrieved by searching a compact GO-term database with its homologous accession number. Subsequently, the GO information is classified by a binary support vector machine (SVM) classifier to determine whether it is a membrane protein or not. If yes, it will be further classified by a multi-label multi-class SVM classifier equipped with an adaptive-decision (AD) scheme to determine to which functional type(s) it belongs. Experimental results show that Mem-ADSVM significantly outperforms state-of-the-art predictors in terms of identifying both membrane proteins and their multi-functional types. This paper also suggests that the two-layer prediction architecture is better than the one-layer for prediction performance. For reader׳s convenience, the Mem-ADSVM server is available online at http://bioinfo.eie.polyu.edu.hk/MemADSVMServer/. PMID:27000774

  19. Protein 4.1, a multifunctional protein of the erythrocyte membrane skeleton: structure and functions in erythrocytes and nonerythroid cells.

    PubMed

    Takakuwa, Y

    2000-10-01

    Protein 4.1 of red blood cells (4.1R) is a multifunctional protein essential for maintaining erythrocyte shape and membrane mechanical properties, such as deformability and stability, through lateral interactions with spectrin and actin in the skeletal network and vertical interactions with cytoplasmic domains of transmembrane proteins, glycophorin C, and band 3. The primary stucture of the major 80-kd isoform of 4.1R has been elucidated, and on the basis of this identification, the functional domains and sites for binding partners have been clarified. Posttranslational modification of 4.1 R, such as phosphorylation and proteolysis, as well as binding of regulatory proteins including calmodulin-Ca2+ to 4.1R, modulates its interactions with other membrane proteins and, consequently, the membrane functions of red blood cells. Alternative splicing occurs in the 4.1R gene, and various isoforms are expressed not only in erythroid but also in nonerythroid cells. This review introduces current knowledge on biochemical, biophysical, genetic, and functional aspects of 4.1R and its family proteins, 4.1G (general type), 4.1B (brain type), and 4.1N (neuron type), recently identified in nonerythroid cells. PMID:11185985

  20. Modular Architecture of Protein Binding Units for Designing Properties of Cellulose Nanomaterials

    PubMed Central

    Malho, Jani-Markus; Arola, Suvi; Laaksonen, Päivi; Szilvay, Géza R; Ikkala, Olli; Linder, Markus B

    2015-01-01

    Molecular biomimetic models suggest that proteins in the soft matrix of nanocomposites have a multimodular architecture. Engineered proteins were used together with nanofibrillated cellulose (NFC) to show how this type of architecture leads to function. The proteins consist of two cellulose-binding modules (CBM) separated by 12-, 24-, or 48-mer linkers. Engineering the linkers has a considerable effects on the interaction between protein and NFC in both wet colloidal state and a dry film. The protein optionally incorporates a multimerizing hydrophobin (HFB) domain connected by another linker. The modular structure explains effects in the hydrated gel state, as well as the deformation of composite materials through stress distribution and crosslinking. Based on this work, strategies can be suggested for tuning the mechanical properties of materials through the coupling of protein modules and their interlinking architectures. PMID:26305491

  1. Potential clinical applications of multi-functional milk proteins and peptides in cancer management.

    PubMed

    Chen, H Y F; Mollstedt, O; Tsai, Men-Hwei; Kreider, R B

    2014-01-01

    The progression of cancer involves multiple changes that alter intracellular signaling to promote cell proliferation. Subsequent remodeling of the tumor microenvironment enhances metastasis by manipulating the immune system. Research in the past decade has shown that milk proteins and peptides are often multi-functional, exerting activities such as anti-microbial, immunomodulatory, cancer cell apoptosis, anti-metastasis, and antioxidant effects. Several milk-derived biologics, such as HAMLET (human α-lactalbumin made lethal to tumor cells) and the human recombinant form of lactoferrin, already demonstrated promising results in clinical trials. Lactoferricin peptide analogs are in early clinical development as antimicrobial agents and cancer immunotherapies. In addition, milk proteins and peptides are well tolerated and many exhibit oral bioavailability; thus they may complement standard therapies to boost overall success in cancer treatments. Lactoferrin, colostrum, and specific milk-derived peptide fractions are currently being developed as clinical nutrition for cancer prevention and chemotherapy protection. This review highlights the potential applications of milk proteins and peptides as pharmaceutical drug candidates and clinical nutrition in the overall management of cancer. PMID:24524762

  2. Comparative analysis of differential network modularity in tissue specific normal and cancer protein interaction networks

    PubMed Central

    2013-01-01

    Background Large scale understanding of complex and dynamic alterations in cellular and subcellular levels during cancer in contrast to normal condition has facilitated the emergence of sophisticated systemic approaches like network biology in recent times. As most biological networks show modular properties, the analysis of differential modularity between normal and cancer protein interaction networks can be a good way to understand cancer more significantly. Two aspects of biological network modularity e.g. detection of molecular complexes (potential modules or clusters) and identification of crucial nodes forming the overlapping modules have been considered in this regard. Methods In the current study, the computational analysis of previously published protein interaction networks (PINs) has been conducted to identify the molecular complexes and crucial nodes of the networks. Protein molecules involved in ten major cancer signal transduction pathways were used to construct the networks based on expression data of five tissues e.g. bone, breast, colon, kidney and liver in both normal and cancer conditions. MCODE (molecular complex detection) and ModuLand methods have been used to identify the molecular complexes and crucial nodes of the networks respectively. Results In case of all tissues, cancer PINs show higher level of clustering (formation of molecular complexes) than the normal ones. In contrast, lower level modular overlapping is found in cancer PINs than the normal ones. Thus a proposition can be made regarding the formation of some giant nodes in the cancer networks with very high degree and resulting in reduced overlapping among the network modules though the predicted molecular complex numbers are higher in cancer conditions. Conclusion The study predicts some major molecular complexes that might act as the important regulators in cancer progression. The crucial nodes identified in this study can be potential drug targets to combat cancer. PMID

  3. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

    PubMed Central

    Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-01-01

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

  4. Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression.

    PubMed Central

    Rao, N K; Shi, G P; Chapman, H A

    1995-01-01

    Binding of urokinase to the glycolipid-anchored urokinase receptor (uPAR) has been implicated in macrophage differentiation. However, no biochemical markers of differentiation have yet been directly linked to uPAR occupancy. As extensive changes in proteolytic profile characterize monocytic differentiation, we have examined the role of uPAR occupancy on protease expression by differentiating phagocytes. Antibodies to either urokinase or to uPAR that prevent receptor binding inhibited induction of cathepsin B in cultured monocytes and both cathepsin B and 92-kD gelatinase mRNA and protein in phorbol diester-stimulated myeloid cells. Mannosamine, an inhibitor of glycolipid anchor assembly, also blocked protease expression. Anti-catalytic urokinase antibodies, excess inactive urokinase, or aprotinin had no effect, indicating that receptor occupancy per se regulated protease expression. Antibodies to the integrins CD11a and CD29 or to the glycolipid-anchored proteins CD14 and CD55 also had no effect. Protease induction was independent of matrix attachment. Antibodies to urokinase or uPAR affected neither the decrease in cathepsin G nor the increase in tumor necrosis factor-alpha in phorbol ester-stimulated cells. These data establish that uPAR is a multifunctional receptor, not only promoting pericellular proteolysis and matrix attachment, but also effecting cysteine- and metallo-protease expression during macrophage differentiation. Images PMID:7615819

  5. A multifunctional protein EWS is essential for early brown fat lineage determination

    PubMed Central

    Park, Jun Hong; Kang, Hong Jun; Kang, Soo Im; Lee, Ji Eun; Hur, Jamie; Ge, Kai; Mueller, Elisabetta; Li, Hongjie; Lee, Byeong-Chel; Lee, Sean Bong

    2013-01-01

    Summary A recent surge in obesity has given impetus to better understand the mechanisms of adipogenesis, particularly brown adipose tissue (BAT) due to its potential utilization for anti-obesity therapy. Postnatal brown adipocytes arise from early muscle-progenitors but how brown fat lineage is determined is not completely understood. Here, we show that a multifunctional protein EWS (Ewing Sarcoma) is essential for determining brown fat lineage during development. BATs from Ews-null embryos and newborns are developmentally arrested. Ews mutant brown preadipocytes fail to differentiate due to loss of Bmp7 expression, a critical early brown adipogenic factor. We demonstrate that EWS, along with its binding partner YBX1 (Y-box binding protein 1), activates Bmp7 transcription. Depletion of either Ews or Ybx1 leads to loss of Bmp7 expression and brown adipogenesis. Remarkably, Ews-null BATs and brown preadipocytes ectopically express myogenic genes. These results demonstrate that EWS is essential for early brown fat lineage determination. PMID:23987512

  6. A multifunctional protein, EWS, is essential for early brown fat lineage determination.

    PubMed

    Park, Jun Hong; Kang, Hong Jun; Kang, Soo Im; Lee, Ji Eun; Hur, Jamie; Ge, Kai; Mueller, Elisabetta; Li, Hongjie; Lee, Byeong-Chel; Lee, Sean Bong

    2013-08-26

    The recent surge in obesity has provided an impetus to better understand the mechanisms of adipogenesis, particularly in brown adipose tissue (BAT) because of its potential utilization for antiobesity therapy. Postnatal brown adipocytes arise from early muscle progenitors, but how brown fat lineage is determined is not completely understood. Here, we show that a multifunctional protein, Ewing Sarcoma (EWS), is essential for determining brown fat lineage during development. BATs from Ews null embryos and newborns are developmentally arrested. Ews mutant brown preadipocytes fail to differentiate due to loss of Bmp7 expression, a critical early brown adipogenic factor. We demonstrate that EWS, along with its binding partner Y-box binding protein 1 (YBX1), activates Bmp7 transcription. Depletion of either Ews or Ybx1 leads to loss of Bmp7 expression and brown adipogenesis. Remarkably, Ews null BATs and brown preadipocytes ectopically express myogenic genes. These results demonstrate that EWS is essential for early brown fat lineage determination. PMID:23987512

  7. Influenza A virus non-structural protein 1 (NS1) interacts with cellular multifunctional protein nucleolin during infection.

    PubMed

    Murayama, Rikinori; Harada, Yuichi; Shibata, Toshikatsu; Kuroda, Kazumichi; Hayakawa, Satoshi; Shimizu, Kazufumi; Tanaka, Torahiko

    2007-11-01

    Influenza A virus non-structural protein 1 (NS1) is the most important viral regulatory factor that controls cellular processes to facilitate viral replication. To gain further insight into the role of NS1, we tried to find novel cellular factors that interact with NS1. The complexes of NS1 and target proteins were pulled down from an infected cell lysate using anti-NS1 (A/Udorn/72) single-chain Fv and identified by peptide mass fingerprinting analysis. We identified nucleolin, a multifunctional major nucleolar protein, as a novel NS1-binding protein. The RNA-binding domain of NS1 was responsible for this binding, as judged by a GST (glutathione S-transferase) pull-down assay with the GST-fused functional domains of NS1. By laser confocal microscopy, we observed the co-localization of NS1 with nucleolin most clearly in the nucleoli, indicating that NS1 is interacting with nucleolin during infection. Our results suggest a novel function of NS1, namely, affecting cellular events via interaction with nucleolin. PMID:17767916

  8. Purification of Regucalcin from the Seminal Vesicular Fluid: A Calcium Binding Multi-Functional Protein.

    PubMed

    Harikrishna, P; Shende, A M; Reena, K K; Thomas, Jobin; Bhure, S K

    2016-08-01

    Regucalcin is a multi-functional protein having roles in calcium homeostasis as well as in anti-apoptotic, anti-prolific and anti-oxidative functions. Recently, it has been reported from the male reproductive tract, but its role in male reproduction needs further investigation; for which the native regucalcin of reproductive origin will be more appropriate. The gel exclusion chromatography followed by diethyl aminoethane cellulose chromatography and two-dimentional cellulose acetate membrane electrophoresis used for its purification are time consuming and less specific. Here, the regucalcin gene from buffalo testis has been cloned, expressed and purified in recombinant form, and subsequently used for raising hyper-immune serum. The Western blot of seminal vesicular fluid probed with anti-regucalcin polyclonal and monoclonal antibodies showed the presence of 28 and 34 kDa bands specific to regucalcin. Further, an affinity matrix has been prepared using anti-regucalcin polyclonal antibodies. An immuno-affinity chromatography method has been standardized to isolate regucalcin from seminal vesicular fluid. The initial complexity of the protein mixture in the seminal vesicular fluid has been reduced by a heat coagulation step. The purified protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a single band at 68 kDa that has been further confirmed as regucalcin by Liquid chromatography-mass spectrometry/mass spectrometry. The RGN purified from seminal vesicular fluid will be more appropriate for studying its possible role in male reproduction, especially sperm cell capacitation, hyperactivation, acrosome reaction and cryopreservation. The study can be applied in purifying regucalcin from different tissues or species with minor modifications in the methodology. PMID:27460579

  9. [The multifunctionality of CHIP protein in the protein quality-control system].

    PubMed

    Lenartowski, Robert; Gumowski, Krzysztof; Goc, Anna

    2008-01-01

    Selective protein degradation depends on their quality being controlled by the cellular system, which includes chaperones involved in protein folding and two degradation systems, the proteasomal and lysosomal. CHIP (carboxyl terminus of Hsp70-interacting protein), an E3 ubiquitin ligase and co-chaperone, serves as a chaperone-degradation system interface. This article reviews the molecular characteristics of CHIP protein, the mechanism of its action, and its role in cellular metabolism and discusses how CHIP dysfunction may lead to neurodegenerative diseases. PMID:18583953

  10. α-Enolase, a Multifunctional Protein: Its Role on Pathophysiological Situations

    PubMed Central

    Díaz-Ramos, Àngels; Roig-Borrellas, Anna; García-Melero, Ana; López-Alemany, Roser

    2012-01-01

    α-Enolase is a key glycolytic enzyme in the cytoplasm of prokaryotic and eukaryotic cells and is considered a multifunctional protein. α-enolase is expressed on the surface of several cell types, where it acts as a plasminogen receptor, concentrating proteolytic plasmin activity on the cell surface. In addition to glycolytic enzyme and plasminogen receptor functions, α-Enolase appears to have other cellular functions and subcellular localizations that are distinct from its well-established function in glycolysis. Furthermore, differential expression of α-enolase has been related to several pathologies, such as cancer, Alzheimer's disease, and rheumatoid arthritis, among others. We have identified α-enolase as a plasminogen receptor in several cell types. In particular, we have analyzed its role in myogenesis, as an example of extracellular remodelling process. We have shown that α-enolase is expressed on the cell surface of differentiating myocytes, and that inhibitors of α-enolase/plasminogen binding block myogenic fusion in vitro and skeletal muscle regeneration in mice. α-Enolase could be considered as a marker of pathological stress in a high number of diseases, performing several of its multiple functions, mainly as plasminogen receptor. This paper is focused on the multiple roles of the α-enolase/plasminogen axis, related to several pathologies. PMID:23118496

  11. Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex

    PubMed Central

    Brandenburg, Jens; Schimanski, Bernd; Nogoceke, Everson; Nguyen, Tu N; Padovan, Júlio C; Chait, Brian T; Cross, George A M; Günzl, Arthur

    2007-01-01

    The vector-borne, protistan parasite Trypanosoma brucei is the only known eukaryote with a multifunctional RNA polymerase I that, in addition to ribosomal genes, transcribes genes encoding the parasite's major cell-surface proteins—the variant surface glycoprotein (VSG) and procyclin. In the mammalian bloodstream, antigenic variation of the VSG coat is the parasite's means to evade the immune response, while procyclin is necessary for effective establishment of trypanosome infection in the fly. Moreover, the exceptionally high efficiency of mono-allelic VSG expression is essential to bloodstream trypanosomes since its silencing caused rapid cell-cycle arrest in vitro and clearance of parasites from infected mice. Here we describe a novel protein complex that recognizes class I promoters and is indispensable for class I transcription; it consists of a dynein light chain and six polypeptides that are conserved only among trypanosomatid parasites. In accordance with an essential transcriptional function of the complex, silencing the expression of a key subunit was lethal to bloodstream trypanosomes and specifically affected the abundance of rRNA and VSG mRNA. The complex was dubbed class I transcription factor A. PMID:17972917

  12. Identification and inhibitory properties of multifunctional peptides from pea protein hydrolysate.

    PubMed

    Li, Huan; Aluko, Rotimi E

    2010-11-10

    Pea protein isolate was hydrolyzed with alcalase, and the hydrolysate passed through a 1 kDa cutoff ultrafiltration membrane. The permeate was freeze-dried and fractionated on a cationic solid-phase extraction (SPE) column. All fractions were tested for their inhibitory activities against angiotensin-converting enzyme (ACE), renin, and calmodulin-dependent phosphodiesterase 1 (CaMPDE). With the exception of the first eluted fraction, inhibitory properties of the SPE fractions against CaMPDE (but not ACE and renin) were directly related to cationic character (residence time on the column). However, the fraction that eluted with 1% ammonium hydroxide (SPE 1%) had the highest peptide yield and was subsequently fractionated using two consecutive rounds of reversed-phase high-performance liquid chromatography to obtain three peaks with major peptides identified as IR, KF, and EF by ultra performance liquid chromatography-tandem mass spectrometry. The three dipeptides showed weak inhibitory properties toward CaMPDE but strong inhibitions (IC50 values <25 mM) of ACE and renin. In general, the peptides had higher potency against ACE than against renin. It is indicated from our results that these peptides may be used as potential ingredients to formulate multifunctional food products and nutraceuticals. PMID:20929253

  13. Early-onset Purkinje cell dysfunction underlies cerebellar ataxia in peroxisomal multifunctional protein-2 deficiency.

    PubMed

    De Munter, Stephanie; Verheijden, Simon; Vanderstuyft, Esther; Malheiro, Ana Rita; Brites, Pedro; Gall, David; Schiffmann, Serge N; Baes, Myriam

    2016-10-01

    The cerebellar pathologies in peroxisomal diseases underscore that these organelles are required for the normal development and maintenance of the cerebellum, but the mechanisms have not been resolved. Here we investigated the origins of the early-onset coordination impairment in a mouse model with neural selective deficiency of multifunctional protein-2, the central enzyme of peroxisomal β-oxidation. At the age of 4weeks, Nestin-Mfp2(-/-) mice showed impaired motor learning on the accelerating rotarod and underperformed on the balance beam test. The gross morphology of the cerebellum and Purkinje cell arborization were normal. However, electrophysiology revealed a reduced Purkinje cell firing rate, a decreased excitability and an increased membrane capacitance. The distribution of climbing and parallel fiber synapses on Purkinje cells was immature and was accompanied by an increased spine length. Despite normal myelination, Purkinje cell axon degeneration was evident from the occurrence of axonal swellings containing accumulated organelles. In conclusion, the electrical activity, axonal integrity and wiring of Purkinje cells are exquisitely dependent on intact peroxisomal β-oxidation in neural cells. PMID:27353294

  14. Structural basis for the modular recognition of single-stranded RNA by PPR proteins

    NASA Astrophysics Data System (ADS)

    Yin, Ping; Li, Quanxiu; Yan, Chuangye; Liu, Ying; Liu, Junjie; Yu, Feng; Wang, Zheng; Long, Jiafu; He, Jianhua; Wang, Hong-Wei; Wang, Jiawei; Zhu, Jian-Kang; Shi, Yigong; Yan, Nieng

    2013-12-01

    Pentatricopeptide repeat (PPR) proteins represent a large family of sequence-specific RNA-binding proteins that are involved in multiple aspects of RNA metabolism. PPR proteins, which are found in exceptionally large numbers in the mitochondria and chloroplasts of terrestrial plants, recognize single-stranded RNA (ssRNA) in a modular fashion. The maize chloroplast protein PPR10 binds to two similar RNA sequences from the ATPI-ATPH and PSAJ-RPL33 intergenic regions, referred to as ATPH and PSAJ, respectively. By protecting the target RNA elements from 5' or 3' exonucleases, PPR10 defines the corresponding 5' and 3' messenger RNA termini. Despite rigorous functional characterizations, the structural basis of sequence-specific ssRNA recognition by PPR proteins remains to be elucidated. Here we report the crystal structures of PPR10 in RNA-free and RNA-bound states at resolutions of 2.85 and 2.45Å, respectively. In the absence of RNA binding, the nineteen repeats of PPR10 are assembled into a right-handed superhelical spiral. PPR10 forms an antiparallel, intertwined homodimer and exhibits considerable conformational changes upon binding to its target ssRNA, an 18-nucleotide PSAJ element. Six nucleotides of PSAJ are specifically recognized by six corresponding PPR10 repeats following the predicted code. The molecular basis for the specific and modular recognition of RNA bases A, G and U is revealed. The structural elucidation of RNA recognition by PPR proteins provides an important framework for potential biotechnological applications of PPR proteins in RNA-related research areas.

  15. Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein.

    PubMed

    Sawicka, Kirsty; Bushell, Martin; Spriggs, Keith A; Willis, Anne E

    2008-08-01

    PTB (polypyrimidine-tract-binding protein) is a ubiquitous RNA-binding protein. It was originally identified as a protein with a role in splicing but it is now known to function in a large number of diverse cellular processes including polyadenylation, mRNA stability and translation initiation. Specificity of PTB function is achieved by a combination of changes in the cellular localization of this protein (its ability to shuttle from the nucleus to the cytoplasm is tightly controlled) and its interaction with additional proteins. These differences in location and trans-acting factor requirements account for the fact that PTB acts both as a suppressor of splicing and an activator of translation. In the latter case, the role of PTB in translation has been studied extensively and it appears that this protein is required for an alternative form of translation initiation that is mediated by a large RNA structural element termed an IRES (internal ribosome entry site) that allows the synthesis of picornaviral proteins and cellular proteins that function to control cell growth and cell death. In the present review, we discuss how PTB regulates these disparate processes. PMID:18631133

  16. Structure-function of the multifunctional Ca2+/calmodulin-dependent protein kinase II.

    PubMed

    Hudmon, Andy; Schulman, Howard

    2002-06-15

    Ca2+/calmodulin (CaM)-dependent protein kinase (CaMKII) is a ubiquitous mediator of Ca2+-linked signalling that phosphorylates a wide range of substrates to co-ordinate and regulate Ca2+-mediated alterations in cellular function. The transmission of information by the kinase from extracellular stimuli and the intracellular Ca2+ rise is not passive. Rather, its multimeric structure and autoregulation enable this enzyme to participate actively in the sensitivity, timing and location of its action. CaMKII can: (i) be activated in a Ca2+-spike frequency-dependent manner; (ii) become independent of its initial Ca2+/CaM activators; and (iii) undergo a 'molecular switch-like' behaviour, which is crucial for certain forms of learning and memory. CaMKII is derived from a family of four homologous but distinct genes, with over 30 alternatively spliced isoforms described at present. These isoforms possess diverse developmental and anatomical expression patterns, as well as subcellular localization. Six independent catalytic/autoregulatory domains are connected by a narrow stalk-like appendage to each hexameric ring within the dodecameric structure. Ca2+/CaM binding activates the enzyme by disinhibiting the autoregulatory domain; this process initiates an intra-holoenzyme autophosphorylation reaction that induces complex changes in the enzyme's sensitivity to Ca2+/CaM, including the generation of Ca2+/CaM-independent (autonomous) activity and marked increase in affinity for CaM. The role of CaMKII in Ca2+ signal transduction is shaped by its autoregulation, isoenzymic type and subcellular localization. The molecular determinants and mechanisms producing these processes are discussed as they relate to the structure-function of this multifunctional protein kinase. PMID:11931644

  17. Structure-function of the multifunctional Ca2+/calmodulin-dependent protein kinase II.

    PubMed Central

    Hudmon, Andy; Schulman, Howard

    2002-01-01

    Ca2+/calmodulin (CaM)-dependent protein kinase (CaMKII) is a ubiquitous mediator of Ca2+-linked signalling that phosphorylates a wide range of substrates to co-ordinate and regulate Ca2+-mediated alterations in cellular function. The transmission of information by the kinase from extracellular stimuli and the intracellular Ca2+ rise is not passive. Rather, its multimeric structure and autoregulation enable this enzyme to participate actively in the sensitivity, timing and location of its action. CaMKII can: (i) be activated in a Ca2+-spike frequency-dependent manner; (ii) become independent of its initial Ca2+/CaM activators; and (iii) undergo a 'molecular switch-like' behaviour, which is crucial for certain forms of learning and memory. CaMKII is derived from a family of four homologous but distinct genes, with over 30 alternatively spliced isoforms described at present. These isoforms possess diverse developmental and anatomical expression patterns, as well as subcellular localization. Six independent catalytic/autoregulatory domains are connected by a narrow stalk-like appendage to each hexameric ring within the dodecameric structure. Ca2+/CaM binding activates the enzyme by disinhibiting the autoregulatory domain; this process initiates an intra-holoenzyme autophosphorylation reaction that induces complex changes in the enzyme's sensitivity to Ca2+/CaM, including the generation of Ca2+/CaM-independent (autonomous) activity and marked increase in affinity for CaM. The role of CaMKII in Ca2+ signal transduction is shaped by its autoregulation, isoenzymic type and subcellular localization. The molecular determinants and mechanisms producing these processes are discussed as they relate to the structure-function of this multifunctional protein kinase. PMID:11931644

  18. Single Adhesive Nanofibers from a Live Diatom Have the Signature Fingerprint of Modular Proteins

    PubMed Central

    Dugdale, T. M.; Dagastine, R.; Chiovitti, A.; Mulvaney, P.; Wetherbee, R.

    2005-01-01

    The adhesive and mechanical properties of a cell-substratum adhesive secreted by live diatom cells were examined in situ using atomic force microscopy. The resulting force curves have a regular saw-tooth pattern, the characteristic fingerprint of modular proteins, and when bridged between tip and surface can repeatedly be stretched and relaxed resulting in precisely overlaying saw-tooth curves (up to ∼600 successive cycles). The average rupture force of the peaks is 0.794 ± 0.007 (mean ± SE) nN at a loading rate of 0.8 μm/s and the average persistence length is 0.026 ± <0.001 (mean ± SE) nm (fit using the worm-like chain model). We propose that we are pulling on single adhesive nanofibers, each a cohesive unit composed of a set number of modular proteins aligned in register. Furthermore, we can observe and differentiate when up to three adhesive nanofibers are pulled based upon multimodal distributions of force and persistence length. The high force required for bond rupture, high extensibility (∼1.2 μm), and the accurate and rapid refolding upon relaxation, together provide strong and flexible properties ideally suited for the cell-substratum adhesion of this fouling diatom and allow us to understand the mechanism responsible for the strength of adhesion. PMID:16169972

  19. ConSole: using modularity of Contact maps to locate Solenoid domains in protein structures

    PubMed Central

    2014-01-01

    Background Periodic proteins, characterized by the presence of multiple repeats of short motifs, form an interesting and seldom-studied group. Due to often extreme divergence in sequence, detection and analysis of such motifs is performed more reliably on the structural level. Yet, few algorithms have been developed for the detection and analysis of structures of periodic proteins. Results ConSole recognizes modularity in protein contact maps, allowing for precise identification of repeats in solenoid protein structures, an important subgroup of periodic proteins. Tests on benchmarks show that ConSole has higher recognition accuracy as compared to Raphael, the only other publicly available solenoid structure detection tool. As a next step of ConSole analysis, we show how detection of solenoid repeats in structures can be used to improve sequence recognition of these motifs and to detect subtle irregularities of repeat lengths in three solenoid protein families. Conclusions The ConSole algorithm provides a fast and accurate tool to recognize solenoid protein structures as a whole and to identify individual solenoid repeat units from a structure. ConSole is available as a web-based, interactive server and is available for download at http://console.sanfordburnham.org. PMID:24766872

  20. Characterization of SMOC-2, a modular extracellular calcium-binding protein.

    PubMed Central

    Vannahme, Christian; Gösling, Silke; Paulsson, Mats; Maurer, Patrik; Hartmann, Ursula

    2003-01-01

    We have isolated the novel gene SMOC-2, which encodes a secreted modular protein containing an EF-hand calcium-binding domain homologous to that in BM-40. It further consists of two thyroglobulin-like domains, a follistatin-like domain and a novel domain found only in the homologous SMOC-1. Phylogenetic analysis of the calcium-binding domain sequences showed that SMOC-1 and -2 form a separate group within the BM-40 family. The human and mouse SMOC-2 sequences are coded for by genes consisting of 13 exons located on chromosomes 6 and 17, respectively. Analysis of recombinantly expressed protein showed that SMOC-2 is a glycoprotein with a calcium-dependent conformation. Results from Northern blots and reverse transcription PCR revealed a widespread expression in many tissues. PMID:12741954

  1. Non-Carrier Nanoparticles Adjuvant Modular Protein Vaccine in a Particle-Dependent Manner

    PubMed Central

    Seth, Arjun; Ritchie, Fiona K.; Wibowo, Nani; Lua, Linda H. L.; Middelberg, Anton P. J.

    2015-01-01

    Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL) nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e) was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing). In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties. PMID:25756283

  2. Non-carrier nanoparticles adjuvant modular protein vaccine in a particle-dependent manner.

    PubMed

    Seth, Arjun; Ritchie, Fiona K; Wibowo, Nani; Lua, Linda H L; Middelberg, Anton P J

    2015-01-01

    Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL) nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e) was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing). In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties. PMID:25756283

  3. Programmable RNA-binding protein composed of repeats of a single modular unit.

    PubMed

    Adamala, Katarzyna P; Martin-Alarcon, Daniel A; Boyden, Edward S

    2016-05-10

    The ability to monitor and perturb RNAs in living cells would benefit greatly from a modular protein architecture that targets unmodified RNA sequences in a programmable way. We report that the RNA-binding protein PumHD (Pumilio homology domain), which has been widely used in native and modified form for targeting RNA, can be engineered to yield a set of four canonical protein modules, each of which targets one RNA base. These modules (which we call Pumby, for Pumilio-based assembly) can be concatenated in chains of varying composition and length, to bind desired target RNAs. The specificity of such Pumby-RNA interactions was high, with undetectable binding of a Pumby chain to RNA sequences that bear three or more mismatches from the target sequence. We validate that the Pumby architecture can perform RNA-directed protein assembly and enhancement of translation of RNAs. We further demonstrate a new use of such RNA-binding proteins, measurement of RNA translation in living cells. Pumby may prove useful for many applications in the measurement, manipulation, and biotechnological utilization of unmodified RNAs in intact cells and systems. PMID:27118836

  4. Fluorogen activating protein-affibody probes: modular, no-wash measurement of epidermal growth factor receptors.

    PubMed

    Wang, Yi; Telmer, Cheryl A; Schmidt, Brigitte F; Franke, Josef D; Ort, Stephan; Arndt-Jovin, Donna J; Bruchez, Marcel P

    2015-01-21

    Fluorescence is essential for dynamic live cell imaging, and affinity reagents are required for quantification of endogenous proteins. Various fluorescent dyes can report on different aspects of biological trafficking, but must be independently conjugated to affinity reagents and characterized for specific biological readouts. Here we present the characterization of a new modular platform for small anti-EGFR affinity probes for studying rapid changes in receptor pools. A protein domain (FAP dL5**) that binds to malachite-green (MG) derivatives for fluorescence activation was expressed as a recombinant fusion to one or two copies of the compact EGFR binding affibody ZEGFR:1907. This is a recombinant and fluorogenic labeling reagent for native EGFR molecules. In vitro fluorescence assays demonstrated that the binding of these dyes to the FAP-affibody fusions produced thousand-fold fluorescence enhancements, with high binding affinity and fast association rates. Flow cytometry assays and fluorescence microscopy demonstrated that these probes label endogenous EGFR on A431 cells without disruption of EGFR function, and low nanomolar surface Kd values were observed with the double-ZEGFR:1907 constructs. The application of light-harvesting fluorogens (dyedrons) significantly improved the detected fluorescence signal. Altering the order of addition of the ligand, probe, and dyes allowed differentiation between surface and endocytotic pools of receptors to reveal the rapid dynamics of endocytic trafficking. Therefore, FAP/affibody coupling provides a new approach to construct compact and modular affinity probes that label endogenous proteins on living cells and can be used for studying rapid changes in receptor pools involved in trafficking. PMID:25490520

  5. Multifunctional nanocrystals

    DOEpatents

    Klimov, Victor I.; Hollingsworth, Jennifer A.; Crooker, Scott A.; Kim, Hyungrak

    2010-06-22

    Multifunctional nanocomposites are provided including a core of either a magnetic material or an inorganic semiconductor, and, a shell of either a magnetic material or an inorganic semiconductor, wherein the core and the shell are of differing materials, such multifunctional nanocomposites having multifunctional properties including magnetic properties from the magnetic material and optical properties from the inorganic semiconductor material. Various applications of such multifunctional nanocomposites are also provided.

  6. Multifunctional nanocrystals

    DOEpatents

    Klimov, Victor I.; Hollingsworth, Jennifer A.; Crooker, Scott A.; Kim, Hyungrak

    2007-08-28

    Multifunctional nanocomposites are provided including a core of either a magnetic material or an inorganic semiconductor, and, a shell of either a magnetic material or an inorganic semiconductor, wherein the core and the shell are of differing materials, such multifunctional nanocomposites having multifunctional properties including magnetic properties from the magnetic material and optical properties from the inorganic semiconductor material. Various applications of such multifunctional nanocomposites are also provided.

  7. Analysis of heat kernel highlights the strongly modular and heat-preserving structure of proteins

    NASA Astrophysics Data System (ADS)

    Livi, Lorenzo; Maiorino, Enrico; Pinna, Andrea; Sadeghian, Alireza; Rizzi, Antonello; Giuliani, Alessandro

    2016-01-01

    In this paper, we study the structure and dynamical properties of protein contact networks with respect to other biological networks, together with simulated archetypal models acting as probes. We consider both classical topological descriptors, such as modularity and statistics of the shortest paths, and different interpretations in terms of diffusion provided by the discrete heat kernel, which is elaborated from the normalized graph Laplacians. A principal component analysis shows high discrimination among the network types, by considering both the topological and heat kernel based vector characterizations. Furthermore, a canonical correlation analysis demonstrates the strong agreement among those two characterizations, providing thus an important justification in terms of interpretability for the heat kernel. Finally, and most importantly, the focused analysis of the heat kernel provides a way to yield insights on the fact that proteins have to satisfy specific structural design constraints that the other considered networks do not need to obey. Notably, the heat trace decay of an ensemble of varying-size proteins denotes subdiffusion, a peculiar property of proteins.

  8. Theory of force-extension curves for modular proteins and DNA hairpins

    NASA Astrophysics Data System (ADS)

    Bonilla, L. L.; Carpio, A.; Prados, A.

    2015-05-01

    We study a model describing the force-extension curves of modular proteins, nucleic acids, and other biomolecules made out of several single units or modules. At a mesoscopic level of description, the configuration of the system is given by the elongations of each of the units. The system free energy includes a double-well potential for each unit and an elastic nearest-neighbor interaction between them. Minimizing the free energy yields the system equilibrium properties whereas its dynamics is given by (overdamped) Langevin equations for the elongations, in which friction and noise amplitude are related by the fluctuation-dissipation theorem. Our results, both for the equilibrium and the dynamical situations, include analytical and numerical descriptions of the system force-extension curves under force or length control and agree very well with actual experiments in biomolecules. Our conclusions also apply to other physical systems comprising a number of metastable units, such as storage systems or semiconductor superlattices.

  9. Theory of force-extension curves for modular proteins and DNA hairpins.

    PubMed

    Bonilla, L L; Carpio, A; Prados, A

    2015-05-01

    We study a model describing the force-extension curves of modular proteins, nucleic acids, and other biomolecules made out of several single units or modules. At a mesoscopic level of description, the configuration of the system is given by the elongations of each of the units. The system free energy includes a double-well potential for each unit and an elastic nearest-neighbor interaction between them. Minimizing the free energy yields the system equilibrium properties whereas its dynamics is given by (overdamped) Langevin equations for the elongations, in which friction and noise amplitude are related by the fluctuation-dissipation theorem. Our results, both for the equilibrium and the dynamical situations, include analytical and numerical descriptions of the system force-extension curves under force or length control and agree very well with actual experiments in biomolecules. Our conclusions also apply to other physical systems comprising a number of metastable units, such as storage systems or semiconductor superlattices. PMID:26066204

  10. Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy

    PubMed Central

    Negro-Demontel, María Luciana; Saccardo, Paolo; Giacomini, Cecilia; Yáñez-Muñoz, Rafael Joaquín; Ferrer-Miralles, Neus; Vazquez, Esther; Villaverde, Antonio; Peluffo, Hugo

    2014-01-01

    Traumatic brain injury (TBI) remains as one of the leading causes of mortality and morbidity worldwide and there are no effective treatments currently available. Gene therapy applications have emerged as important alternatives for the treatment of diverse nervous system injuries. New strategies are evolving with the notion that each particular pathological condition may require a specific vector. Moreover, the lack of detailed comparative studies between different vectors under similar conditions hampers the selection of an ideal vector for a given pathological condition. The potential use of lentiviral vectors versus several modular protein-based nanovectors was compared using a controlled cortical impact model of TBI under the same gene therapy conditions. We show that variables such as protein/DNA ratio, incubation volume, and presence of serum or chloroquine in the transfection medium impact on both nanovector formation and transfection efficiency in vitro. While lentiviral vectors showed GFP protein 1 day after TBI and increased expression at 14 days, nanovectors showed stable and lower GFP transgene expression from 1 to 14 days. No toxicity after TBI by any of the vectors was observed as determined by resulting levels of IL-1β or using neurological sticky tape test. In fact, both vector types induced functional improvement per se. PMID:26015985

  11. Multifunctional cellulase and hemicellulase

    SciTech Connect

    Fox, Brian G.; Takasuka, Taichi; Bianchetti, Christopher M.

    2015-09-29

    A multifunctional polypeptide capable of hydrolyzing cellulosic materials, xylan, and mannan is disclosed. The polypeptide includes the catalytic core (cc) of Clostridium thermocellum Cthe_0797 (CelE), the cellulose-specific carbohydrate-binding module CBM3 of the cellulosome anchoring protein cohesion region (CipA) of Clostridium thermocellum (CBM3a), and a linker region interposed between the catalytic core and the cellulose-specific carbohydrate binding module. Methods of using the multifunctional polypeptide are also disclosed.

  12. An affinity-based scoring scheme for predicting DNA-binding activities of modularly assembled zinc-finger proteins

    PubMed Central

    Sander, Jeffry D.; Zaback, Peter; Joung, J. Keith; Voytas, Daniel F.; Dobbs, Drena

    2009-01-01

    Zinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this ‘modular assembly’ approach do not always function well in vivo. Here we report a modular assembly scoring strategy that both identifies combinations of modules least likely to function efficiently in vivo and provides accurate estimates of their relative binding affinities in vitro. Predicted binding affinities for 53 ‘three-finger’ ZFPs, computed based on energy contributions of the constituent modules, were highly correlated (r = 0.80) with activity levels measured in bacterial two-hybrid assays. Moreover, Kd values for seven modularly assembled ZFPs and their intended targets, measured using fluorescence anisotropy, were also highly correlated with predictions (r = 0.91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here. PMID:19056825

  13. Multifunctionality of Acidulated Serum Albumin on Inhibiting Zn²⁺-Mediated Amyloid β-Protein Fibrillogenesis and Cytotoxicity.

    PubMed

    Xie, Baolong; Dong, Xiaoyan; Wang, Yongjian; Sun, Yan

    2015-07-01

    Fibrillogenesis of amyloid β-proteins (Aβ) mediated by transition-metal ions such as Zn(2+) in neuronal cells plays a causative role in Alzheimer's disease. Hence, it is highly desired to design multifunctional agents capable of inhibiting Aβ aggregation and modulating metal-Aβ species. In this study, we fabricated acidulated human serum albumin (A-HSA) as a multifunctional agent for binding Zn(2+) and modulating Zn(2+)-mediated Aβ fibrillogenesis and cytotoxicity. On average, 19.5 diglycolic anhydrides were modified onto the surface of human serum albumin (HSA). It was confirmed that A-HSA kept the stability and biocompatibility of native HSA. Moreover, it could inhibit Aβ42 fibrillogenesis and change the pathway of Zn(2+)-mediated Aβ42 aggregation, as demonstrated by extensive biophysical assays. In addition, upon incubation with A-HSA, the cytotoxicity presented by Zn(2+)-Aβ42 aggregates was significantly mitigated in living cells. The results showed that A-HSA had much stronger inhibitory effect on Zn(2+)-mediated Aβ42 fibrillogenesis and cytotoxicity than equimolar HSA. Isothermal titration calorimetry and stopped-flow fluorescence measurements were then performed to investigate the working mechanism of A-HSA. The studies showed that the A-HSA surface, with more negative charges, not only had stronger affinity for Zn(2+) but also might decrease the binding affinity of Aβ42 for Zn(2+). Moreover, hydrophobic binding and electrostatic repulsion could work simultaneously on the bound Aβ42 on the A-HSA surface. As a result, Aβ42 conformations could be stretched, which avoided the formation of toxic Zn(2+)-Aβ42 aggregates. The research thus revealed that A-HSA is a multifunctional agent capable of altering the pathway of Zn(2+)-mediated Aβ42 aggregation and greatly mitigating the amyloid cytotoxicity. PMID:26070334

  14. Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications.

    PubMed

    Lee, Moo-Seung; Koo, Sunwoo; Jeong, Dae Gwin; Tesh, Vernon L

    2016-01-01

    Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are primary virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications, such as hemolytic uremic syndrome and central nervous system abnormalities. Current therapeutic options to treat patients infected with toxin-producing bacteria are limited. The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. However, in the last decade, numerous studies have demonstrated that in addition to being potent protein synthesis inhibitors, Stxs are also multifunctional proteins capable of activating multiple cell stress signaling pathways, which may result in apoptosis, autophagy or activation of the innate immune response. Here, we briefly present the current understanding of Stx-activated signaling pathways and provide a concise review of therapeutic applications to target tumors by engineering the toxins. PMID:26999205

  15. Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications

    PubMed Central

    Lee, Moo-Seung; Koo, Sunwoo; Jeong, Dae Gwin; Tesh, Vernon L.

    2016-01-01

    Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are primary virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications, such as hemolytic uremic syndrome and central nervous system abnormalities. Current therapeutic options to treat patients infected with toxin-producing bacteria are limited. The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. However, in the last decade, numerous studies have demonstrated that in addition to being potent protein synthesis inhibitors, Stxs are also multifunctional proteins capable of activating multiple cell stress signaling pathways, which may result in apoptosis, autophagy or activation of the innate immune response. Here, we briefly present the current understanding of Stx-activated signaling pathways and provide a concise review of therapeutic applications to target tumors by engineering the toxins. PMID:26999205

  16. Self-assembly and modular functionalization of three-dimensional crystals from oppositely charged proteins

    PubMed Central

    Liljeström, Ville; Mikkilä, Joona; Kostiainen, Mauri A.

    2014-01-01

    Multicomponent crystals and nanoparticle superlattices are a powerful approach to integrate different materials into ordered nanostructures. Well-developed, especially DNA-based, methods for their preparation exist, yet most techniques concentrate on molecular and synthetic nanoparticle systems in non-biocompatible environment. Here we describe the self-assembly and characterization of binary solids that consist of crystalline arrays of native biomacromolecules. We electrostatically assembled cowpea chlorotic mottle virus particles and avidin proteins into heterogeneous crystals, where the virus particles adopt a non-close-packed body-centred cubic arrangement held together by avidin. Importantly, the whole preparation process takes place at room temperature in a mild aqueous medium allowing the processing of delicate biological building blocks into ordered structures with lattice constants in the nanometre range. Furthermore, the use of avidin–biotin interaction allows highly selective pre- or post-functionalization of the protein crystals in a modular way with different types of functional units, such as fluorescent dyes, enzymes and plasmonic nanoparticles. PMID:25033911

  17. Self-assembly and modular functionalization of three-dimensional crystals from oppositely charged proteins

    NASA Astrophysics Data System (ADS)

    Liljeström, Ville; Mikkilä, Joona; Kostiainen, Mauri A.

    2014-07-01

    Multicomponent crystals and nanoparticle superlattices are a powerful approach to integrate different materials into ordered nanostructures. Well-developed, especially DNA-based, methods for their preparation exist, yet most techniques concentrate on molecular and synthetic nanoparticle systems in non-biocompatible environment. Here we describe the self-assembly and characterization of binary solids that consist of crystalline arrays of native biomacromolecules. We electrostatically assembled cowpea chlorotic mottle virus particles and avidin proteins into heterogeneous crystals, where the virus particles adopt a non-close-packed body-centred cubic arrangement held together by avidin. Importantly, the whole preparation process takes place at room temperature in a mild aqueous medium allowing the processing of delicate biological building blocks into ordered structures with lattice constants in the nanometre range. Furthermore, the use of avidin-biotin interaction allows highly selective pre- or post-functionalization of the protein crystals in a modular way with different types of functional units, such as fluorescent dyes, enzymes and plasmonic nanoparticles.

  18. A modular toolkit to inhibit proline-rich motif–mediated protein–protein interactions

    PubMed Central

    Opitz, Robert; Müller, Matthias; Reuter, Cédric; Barone, Matthias; Soicke, Arne; Roske, Yvette; Piotukh, Kirill; Huy, Peter; Beerbaum, Monika; Wiesner, Burkhard; Beyermann, Michael; Schmieder, Peter; Freund, Christian; Volkmer, Rudolf; Oschkinat, Hartmut; Schmalz, Hans-Günther; Kühne, Ronald

    2015-01-01

    Small-molecule competitors of protein–protein interactions are urgently needed for functional analysis of large-scale genomics and proteomics data. Particularly abundant, yet so far undruggable, targets include domains specialized in recognizing proline-rich segments, including Src-homology 3 (SH3), WW, GYF, and Drosophila enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. Here, we present a modular strategy to obtain an extendable toolkit of chemical fragments (ProMs) designed to replace pairs of conserved prolines in recognition motifs. As proof-of-principle, we developed a small, selective, peptidomimetic inhibitor of Ena/VASP EVH1 domain interactions. Highly invasive MDA MB 231 breast-cancer cells treated with this ligand showed displacement of VASP from focal adhesions, as well as from the front of lamellipodia, and strongly reduced cell invasion. General applicability of our strategy is illustrated by the design of an ErbB4-derived ligand containing two ProM-1 fragments, targeting the yes-associated protein 1 (YAP1)-WW domain with a fivefold higher affinity. PMID:25848013

  19. Arc is a flexible modular protein capable of reversible self-oligomerization

    PubMed Central

    Myrum, Craig; Baumann, Anne; Bustad, Helene J.; Flydal, Marte Innselset; Mariaule, Vincent; Alvira, Sara; Cuéllar, Jorge; Haavik, Jan; Soulé, Jonathan; Valpuesta, José Maria; Márquez, José Antonio; Martinez, Aurora; Bramham, Clive R.

    2015-01-01

    The immediate early gene product Arc (activity-regulated cytoskeleton-associated protein) is posited as a master regulator of long-term synaptic plasticity and memory. However, the physicochemical and structural properties of Arc have not been elucidated. In the present study, we expressed and purified recombinant human Arc (hArc) and performed the first biochemical and biophysical analysis of hArc's structure and stability. Limited proteolysis assays and MS analysis indicate that hArc has two major domains on either side of a central more disordered linker region, consistent with in silico structure predictions. hArc's secondary structure was estimated using CD, and stability was analysed by CD-monitored thermal denaturation and differential scanning fluorimetry (DSF). Oligomerization states under different conditions were studied by dynamic light scattering (DLS) and visualized by AFM and EM. Biophysical analyses show that hArc is a modular protein with defined secondary structure and loose tertiary structure. hArc appears to be pyramid-shaped as a monomer and is capable of reversible self-association, forming large soluble oligomers. The N-terminal domain of hArc is highly basic, which may promote interaction with cytoskeletal structures or other polyanionic surfaces, whereas the C-terminal domain is acidic and stabilized by ionic conditions that promote oligomerization. Upon binding of presenilin-1 (PS1) peptide, hArc undergoes a large structural change. A non-synonymous genetic variant of hArc (V231G) showed properties similar to the wild-type (WT) protein. We conclude that hArc is a flexible multi-domain protein that exists in monomeric and oligomeric forms, compatible with a diverse, hub-like role in plasticity-related processes. PMID:25748042

  20. A modular approach to multifunctional polypeptide/ceramic fluorapatite-based self-assembled system in affinity chromatography for the purification of human Immunoglobulin G.

    PubMed

    Islam, Tuhidul; Fernández-Lahore, Marcelo

    2015-03-01

    The multifunctional bone sialoprotein/apatite (AP) self-assembled systems in the mineralized tissues show a pathway for the noncovalent immobilization of ligands on the AP chromatographic matrix. A model approach is presented here regarding the physical immobilization of ligands on the ceramic fluorapatite (CFT) matrix for the purification of human Immunoglobulin G (hIgG). The peptide pIC, HWRGWV-KPRSVSG, composed of a hIgG-specific peptide, HWRGWV (pLI), and a CFT-specific peptide, KPRSVSG (pTC), was synthesized and subjected to physicochemical characterization. A circular dichroism study showed that pIC possesses a flexible structural feature, which is significant in terms of its multifunctional activities. With the current approach, hIgG will be retained selectively by the self-assembled pIC/CFT column, while other biomolecules will pass through the column without being interacted. Therefore, the chromatographic conditions that are the key factors for the successful implementation of this technique were optimized as a function of the composition and pH of the mobile phase. Here, 115 mM sodium chloride (NaCl) in 20 mM sodium phosphate, pH 7.4, was used as the binding buffer, and the elution was performed with 225 mM NaCl in 20 mM sodium phosphate containing 0.3% w/v sodium acetate at pH 6. The binding capacity of the pIC/CFT column was 21.5 mg hIgG/ml matrix with a ligand density of 18.8 µmol/ml, and the binding capacity of the column increased with the increment of ligand density. Afterward, the applicability of a spacer arm between pLI and pTC was also verified. The hIgG-binding capacity of the column decreased with the increment in size of the spacer. In conclusion, the peptide-mediated self-assembled biomimetic system can be used as an alternative to the chemical immobilization of ligands in order to prevent unwanted consequences that result from some of the conventional ligand coupling chemistry. PMID:25663265

  1. Characterization of binding preference of polyhydroxyalkanoate biosynthesis-related multifunctional protein PhaM from Ralstonia eutropha.

    PubMed

    Ushimaru, Kazunori; Tsuge, Takeharu

    2016-05-01

    The binding preference of a polyhydroxyalkanoate (PHA) biosynthesis-related multifunctional protein from Ralstonia eutropha (PhaMRe) was characterized. In vitro activity assay showed that PHA synthase from R. eutropha (PhaCRe) was activated by the presence of PhaMRe but PHA synthase from Aeromonas caviae (PhaCAc) was not. Additionally, in vitro assays of protein-protein interactions demonstrated that PhaMRe interacted with PhaCRe directly, but did not interact with PhaCAc. These results suggest that the protein-protein interaction is important for the activation of PhaC by PhaMRe. Further analyses indicated that PhaMRe has little or no direct interaction with the PHA polymer chain. Subsequently, PHA biosynthesis genes (phaA Re, phaB Re, and phaC Re/phaC Ac) and the phaM Re gene were introduced into recombinant Escherichia coli and cultivated for PHA accumulation. Contrary to our expectations, the expression of PhaMRe decreased PHA accumulation and changed the morphology of PHA granules to be microscopically obscure shape in PhaCRe-expressing E. coli. No change in the amount of P(3HB) or the morphology of granules by PhaMRe expression was observed in PhaCAc-expressing E. coli. These observations suggest that PhaMRe affects cellular physiology through the PhaM-PhaC interaction. PMID:26728018

  2. A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.

    PubMed

    Pang, Yan; Liu, Jinyao; Qi, Yizhi; Li, Xinghai; Chilkoti, Ashutosh

    2016-08-22

    A versatile method is described to engineer precisely defined protein/peptide-polymer therapeutics by a modular approach that consists of three steps: 1) fusion of a protein/peptide of interest with an elastin-like polypeptide that enables facile purification and high yields; 2) installation of a clickable group at the C terminus of the recombinant protein/peptide with almost complete conversion by enzyme-mediated ligation; and 3) attachment of a polymer by a click reaction with near-quantitative conversion. We demonstrate that this modular approach is applicable to various protein/peptide drugs and used it to conjugate them to structurally diverse water-soluble polymers that prolong the plasma circulation duration of these proteins. The protein/peptide-polymer conjugates exhibited significantly improved pharmacokinetics and therapeutic effects over the native protein/peptide upon administration to mice. The studies reported here provide a facile method for the synthesis of protein/peptide-polymer conjugates for therapeutic use and other applications. PMID:27439953

  3. DNA translocation activity of the multifunctional replication protein ORF904 from the archaeal plasmid pRN1

    PubMed Central

    Sanchez, Martin; Drechsler, Markus; Stark, Holger; Lipps, Georg

    2009-01-01

    The replication protein ORF904 from the plasmid pRN1 is a multifunctional enzyme with ATPase-, primase- and DNA polymerase activity. Sequence analysis suggests the presence of at least two conserved domains: an N-terminal prim/pol domain with primase and DNA polymerase activities and a C-terminal superfamily 3 helicase domain with a strong double-stranded DNA dependant ATPase activity. The exact molecular function of the helicase domain in the process of plasmid replication remains unclear. Potentially this motor protein is involved in duplex remodelling and/or origin opening at the plasmid replication origin. In support of this we found that the monomeric replication protein ORF904 forms a hexameric ring in the presence of DNA. It is able to translocate along single-stranded DNA in 3′–5′ direction as well as on double-stranded DNA. Critical residues important for ATPase activity and DNA translocation activity were identified and are in agreement with a homology model of the helicase domain. In addition we propose that a winged helix DNA-binding domain at the C-terminus of the helicase domain could assist the binding of the replication protein specifically to the replication origin. PMID:19762479

  4. Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase

    NASA Astrophysics Data System (ADS)

    Wagner, John A.; Cozens, Alison L.; Schulman, Howard; Gruenert, Dieter C.; Stryer, Lubert; Gardner, Phyllis

    1991-02-01

    CYSTIC fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells. These channels in normal cells are activated by cyclic AMP-dependent protein kinase1,2 and protein kinase C3,4. In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels1-4. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. We find that intracellular application of activated kinase and ATP activates a Cl- current similar to that activated by a Ca2+ ionophore, that peptide inhibitors of either the kinase or calmodulin block Ca2+-dependent activation of Cl- channels, and that a peptide inhibitor of protein kinase C does not block Ca2+-dependent activation. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis.

  5. Antimicrobial Lactoferrin Peptides: The Hidden Players in the Protective Function of a Multifunctional Protein

    PubMed Central

    Sinha, Mau; Kaushik, Sanket; Kaur, Punit; Singh, Tej P.

    2013-01-01

    Lactoferrin is a multifunctional, iron-binding glycoprotein which displays a wide array of modes of action to execute its primary antimicrobial function. It contains various antimicrobial peptides which are released upon its hydrolysis by proteases. These peptides display a similarity with the antimicrobial cationic peptides found in nature. In the current scenario of increasing resistance to antibiotics, there is a need for the discovery of novel antimicrobial drugs. In this context, the structural and functional perspectives on some of the antimicrobial peptides found in N-lobe of lactoferrin have been reviewed. This paper provides the comparison of lactoferrin peptides with other antimicrobial peptides found in nature as well as interspecies comparison of the structural properties of these peptides within the native lactoferrin. PMID:23554820

  6. Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import.

    PubMed

    Paila, Yamuna D; Richardson, Lynn Gl; Inoue, Hitoshi; Parks, Elizabeth S; McMahon, James; Inoue, Kentaro; Schnell, Danny J

    2016-01-01

    Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated β-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. PMID:26999824

  7. Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import

    PubMed Central

    Paila, Yamuna D; Richardson, Lynn GL; Inoue, Hitoshi; Parks, Elizabeth S; McMahon, James; Inoue, Kentaro; Schnell, Danny J

    2016-01-01

    Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated β-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. DOI: http://dx.doi.org/10.7554/eLife.12631.001 PMID:26999824

  8. Mouse Spam1 (PH-20) is a multifunctional protein: evidence for its expression in the female reproductive tract.

    PubMed

    Zhang, Hong; Martin-DeLeon, Patricia A

    2003-08-01

    Sperm adhesion molecule 1 (Spam1) is a widely conserved sperm surface protein with multiple roles in mammalian fertilization. Although the gene for this protein has been thought to be testis specific based on Northern blot analysis, there is evidence for nontesticular expression when transcripts are analyzed by more sensitive techniques. In the present investigation, results of a reverse transcription polymerase chain reaction assay, an RNase-protection assay (RPA), and an in situ transcript hybridization assay revealed that the murine Spam1 gene is transcribed in the female genital tract. RPA revealed that Spam1 transcripts are synthesized in a region-dependent manner, with the oviduct having lower transcript levels than the uterus and vagina. The transcripts levels were 3- to 10-fold lower in the female genital tract than in the testis. In situ transcript hybridization assay revealed RNA in the luminal epithelium in all three regions of the genital tract and in the uterine myometrium and the oviductal mesothelium. Western blot analysis and immunohistochemistry demonstrated that the protein concentration is 1.5- to 3-fold lower in female tissues than in sperm, and localization is similar to that of the transcripts. The protein has hyaluronidase activity at neutral pH, which is unique for sperm hyaluronidase, but not at acidic pH. In the uterus, Spam1 expression fluctuated during the estrous cycle. Its localization suggests that in addition to functioning as a secretory protein, it may be involved in hyaluronic acid metabolism or turnover in the female genital tract. Our results provide further evidence that Spam1 is a multifunctional protein and that it is less restricted in its expression than previously reported. PMID:12672666

  9. Phosphorylation of sites 3 and 2 in rabbit skeletal muscle glycogen synthase by a multifunctional protein kinase (ATP-citrate lyase kinase)

    SciTech Connect

    Sheorain, V.S.; Ramakrishna, S.; Benjamin, W.B.; Soderling, T.R.

    1985-10-05

    A multifunctional protein kinase, purified from rat liver as ATP-citrate lyase kinase, has been identified as a glycogen synthase kinase. This kinase catalyzed incorporation of up to 1.5 mol of and)2numberSPO4/mol of synthase subunit associated with a decrease in the glycogen synthase activity ratio from 0.85 to a value of 0.15. Approximately 65-70% of the TUPO4 was incorporated into site 3 and 30-35% into site 2 as determined by reverse phase high performance liquid chromatography. This multifunctional kinase was distinguished from glycogen synthase kinase-3 on the basis of nucleotide and protein substrate specificities. Since the phosphate contents in glycogen synthase of sites 3 and 2 are altered in diabetes and by insulin administration, the possible involvement of the multifunctional kinase was explored. Glycogen synthase purified from diabetic rabbits was phosphorylated in vitro by this multifunctional kinase at only 10% of the rate compared to synthase purified from control rabbits. Treatment of the diabetics with insulin restored the synthase to a form that was readily phosphorylated in vitro.

  10. De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity.

    PubMed

    Boyken, Scott E; Chen, Zibo; Groves, Benjamin; Langan, Robert A; Oberdorfer, Gustav; Ford, Alex; Gilmore, Jason M; Xu, Chunfu; DiMaio, Frank; Pereira, Jose Henrique; Sankaran, Banumathi; Seelig, Georg; Zwart, Peter H; Baker, David

    2016-05-01

    In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins. PMID:27151862

  11. A Compact, Multifunctional Fusion Module Directs Cholesterol-Dependent Homomultimerization and Syncytiogenic Efficiency of Reovirus p10 FAST Proteins

    PubMed Central

    Key, Tim; Duncan, Roy

    2014-01-01

    The homologous p10 fusion-associated small transmembrane (FAST) proteins of the avian (ARV) and Nelson Bay (NBV) reoviruses are the smallest known viral membrane fusion proteins, and are virulence determinants of the fusogenic reoviruses. The small size of FAST proteins is incompatible with the paradigmatic membrane fusion pathway proposed for enveloped viral fusion proteins. Understanding how these diminutive viral fusogens mediate the complex process of membrane fusion is therefore of considerable interest, from both the pathogenesis and mechanism-of-action perspectives. Using chimeric ARV/NBV p10 constructs, the 36–40-residue ectodomain was identified as the major determinant of the differing fusion efficiencies of these homologous p10 proteins. Extensive mutagenic analysis determined the ectodomain comprises two distinct, essential functional motifs. Syncytiogenesis assays, thiol-specific surface biotinylation, and liposome lipid mixing assays identified an ∼25-residue, N-terminal motif that dictates formation of a cystine loop fusion peptide in both ARV and NBV p10. Surface immunofluorescence staining, FRET analysis and cholesterol depletion/repletion studies determined the cystine loop motif is connected through a two-residue linker to a 13-residue membrane-proximal ectodomain region (MPER). The MPER constitutes a second, independent motif governing reversible, cholesterol-dependent assembly of p10 multimers in the plasma membrane. Results further indicate that: (1) ARV and NBV homomultimers segregate to distinct, cholesterol-dependent microdomains in the plasma membrane; (2) p10 homomultimerization and cholesterol-dependent microdomain localization are co-dependent; and (3) the four juxtamembrane MPER residues present in the multimerization motif dictate species-specific microdomain association and homomultimerization. The p10 ectodomain therefore constitutes a remarkably compact, multifunctional fusion module that directs syncytiogenic efficiency and

  12. Scalable Production of a Multifunctional Protein (TSG-6) That Aggregates with Itself and the CHO Cells That Synthesize It.

    PubMed

    Kim, Dong-Ki; Choi, Hosoon; Nishida, Hidetaka; Oh, Joo Youn; Gregory, Carl; Lee, Ryang Hwa; Yu, Ji Min; Watanabe, Jun; An, Su Yeon; Bartosh, Thomas J; Prockop, Darwin J

    2016-01-01

    TNF-α stimulated gene/protein 6 (TNFAIP6/TSG-6) is a multifunctional protein that has a number of potential therapeutic applications. Experiments and clinical trials with TSG-6, however, have been limited by the technical difficulties of producing the recombinant protein. We prepared stable clones of CHO cells that expressed recombinant human TSG-6 (rhTSG-6) as a secreted glycoprotein. Paradoxically, both cell number and protein production decreased dramatically when the clones were expanded. The decreases occurred because the protein aggregated the synthesizing CHO cells by binding to the brush border of hyaluronan that is found around many cultured cells. In addition, the rhTSG-6 readily self-aggregated. To address these problems, we added to the medium an inhibitor of hyaluronan synthesis and heparin to compete with the binding of TSG-6 to hyaluronan. Also, we optimized the composition of the culture medium, and transferred the CHO cells from a spinner culture system to a bioreactor that controlled pH and thereby decreased pH-dependent binding properties of the protein. With these and other improvements in the culture conditions, we obtained 57.0 mg ± 9.16 S.D. of rhTSG-6 in 5 or 6 liter of medium. The rhTSG-6 accounted for 18.0% ± 3.76 S.D. of the total protein in the medium. We then purified the protein with a Ni-chelate column that bound the His tag engineered into the C-terminus of the protein followed by an anion exchange column. The yield of the purified monomeric rhTSG-6 was 4.1 mg to 5.6 mg per liter of culture medium. After intravenous injection into mice, the protein had a longer plasma half-life than commercially available rhTSG-6 isolated from a mammalian cell lysate, apparently because it was recovered as a secreted glycoprotein. The bioactivity of the rhTSG-6 in suppressing inflammation was demonstrated in a murine model. PMID:26793973

  13. Scalable Production of a Multifunctional Protein (TSG-6) That Aggregates with Itself and the CHO Cells That Synthesize It

    PubMed Central

    Kim, Dong-Ki; Choi, Hosoon; Nishida, Hidetaka; Oh, Joo Youn; Gregory, Carl; Lee, Ryang Hwa; Yu, Ji Min; Watanabe, Jun; An, Su Yeon; Bartosh, Thomas J.; Prockop, Darwin J.

    2016-01-01

    TNF-α stimulated gene/protein 6 (TNFAIP6/TSG-6) is a multifunctional protein that has a number of potential therapeutic applications. Experiments and clinical trials with TSG-6, however, have been limited by the technical difficulties of producing the recombinant protein. We prepared stable clones of CHO cells that expressed recombinant human TSG-6 (rhTSG-6) as a secreted glycoprotein. Paradoxically, both cell number and protein production decreased dramatically when the clones were expanded. The decreases occurred because the protein aggregated the synthesizing CHO cells by binding to the brush border of hyaluronan that is found around many cultured cells. In addition, the rhTSG-6 readily self-aggregated. To address these problems, we added to the medium an inhibitor of hyaluronan synthesis and heparin to compete with the binding of TSG-6 to hyaluronan. Also, we optimized the composition of the culture medium, and transferred the CHO cells from a spinner culture system to a bioreactor that controlled pH and thereby decreased pH-dependent binding properties of the protein. With these and other improvements in the culture conditions, we obtained 57.0 mg ± 9.16 S.D. of rhTSG-6 in 5 or 6 liter of medium. The rhTSG-6 accounted for 18.0% ± 3.76 S.D. of the total protein in the medium. We then purified the protein with a Ni-chelate column that bound the His tag engineered into the C-terminus of the protein followed by an anion exchange column. The yield of the purified monomeric rhTSG-6 was 4.1 mg to 5.6 mg per liter of culture medium. After intravenous injection into mice, the protein had a longer plasma half-life than commercially available rhTSG-6 isolated from a mammalian cell lysate, apparently because it was recovered as a secreted glycoprotein. The bioactivity of the rhTSG-6 in suppressing inflammation was demonstrated in a murine model. PMID:26793973

  14. Listeria monocytogenes CtaP is a multifunctional cysteine transport-associated protein required for bacterial pathogenesis

    PubMed Central

    Xayarath, Bobbi; Marquis, Hélène; Port, Gary C.; Freitag, Nancy E.

    2009-01-01

    Summary The bacterial pathogen Listeria monocytogenes survives under a myriad of conditions in the outside environment and within the human host where infections can result in severe disease. Bacterial life within the host requires the expression of genes with roles in nutrient acquisition as well as the biosynthesis of bacterial products required to support intracellular growth. A gene product identified as the substrate-binding component of a novel oligopeptide transport system (encoded by lmo0135) was recently shown to be required for L. monocytogenes virulence. Here we demonstrate that lmo0135 encodes a multifunctional protein that is associated with cysteine transport, acid resistance, bacterial membrane integrity, and adherence to host cells. The lmo0135 gene product (designated CtaP, for cysteine transport associated protein) was required for bacterial growth in the presence of low concentrations of cysteine in vitro, but was not required for bacterial replication within the host cytosol. Loss of CtaP increased membrane permeability and acid sensitivity, and reduced bacterial adherence to host cells. ctaP deletion mutants were severely attenuated following intragastric and intravenous inoculation of mice. Taken together, the data presented indicates that CtaP contributes to multiple facets of L. monocytogenes physiology, growth, and survival both inside and outside of animal cells. PMID:19818015

  15. Modular Detection of GFP-Labeled Proteins for Rapid Screening by Electron Microscopy in Cells and Organisms.

    PubMed

    Ariotti, Nicholas; Hall, Thomas E; Rae, James; Ferguson, Charles; McMahon, Kerrie-Ann; Martel, Nick; Webb, Robyn E; Webb, Richard I; Teasdale, Rohan D; Parton, Robert G

    2015-11-23

    Reliable and quantifiable high-resolution protein localization is critical for understanding protein function. However, the time required to clone and characterize any protein of interest is a significant bottleneck, especially for electron microscopy (EM). We present a modular system for enzyme-based protein tagging that allows for improved speed and sampling for analysis of subcellular protein distributions using existing clone libraries to EM-resolution. We demonstrate that we can target a modified soybean ascorbate peroxidase (APEX) to any GFP-tagged protein of interest by engineering a GFP-binding peptide (GBP) directly to the APEX-tag. We demonstrate that APEX-GBP (1) significantly reduces the time required to characterize subcellular protein distributions of whole libraries to less than 3 days, (2) provides remarkable high-resolution localization of proteins to organelle subdomains, and (3) allows EM localization of GFP-tagged proteins, including proteins expressed at endogenous levels, in vivo by crossing existing GFP-tagged transgenic zebrafish lines with APEX-GBP transgenic lines. PMID:26585296

  16. p204, a p200 family protein, as a multifunctional regulator of cell proliferation and differentiation

    PubMed Central

    Luan, Yi; Lengyel, Peter; Liu, Chuan-Ju

    2015-01-01

    The interferon-inducible p200 family comprises a group of homologous mouse and human proteins. Most of these have an N-terminal DAPIN domain and one or two partially conserved, 200 amino acid long C-terminal domains (designated as 200X domain). These proteins play important roles in the regulation of cell proliferation, tissue differentiation, apoptosis and senescence. p200 family proteins are involved also in autoimmunity and the control of tumor growth. These proteins function by binding to various target proteins (e.g. transcription factors, signaling proteins, oncoproteins and tumor suppressor proteins) and modulating target activity. This review concentrates on p204, a murine member of the family and its roles in regulating cell proliferation, cell and tissue differentiation (e.g. of skeletal muscle myotubes, beating cardiac myocytes, osteoblasts, chondrocytes and macrophages) and signaling by Ras proteins. The expression of p204 in various tissues as promoted by tissue-specific transcription factors, its distribution among subcellular compartments, and the controls of these features are also discussed. PMID:19027346

  17. The Multifunctions of WD40 Proteins in Genome Integrity and Cell Cycle Progression

    PubMed Central

    Zhang, Caiguo; Zhang, Fan

    2015-01-01

    Eukaryotic genome encodes numerous WD40 repeat proteins, which generally function as platforms of protein-protein interactions and are involved in numerous biological process, such as signal transduction, gene transcriptional regulation, protein modifications, cytoskeleton assembly, vesicular trafficking, DNA damage and repair, cell death and cell cycle progression. Among these diverse functions, genome integrity maintenance and cell cycle progression are extremely important as deregulation of them is clinically linked to uncontrolled proliferative diseases such as cancer. Thus, we mainly summarize and discuss the recent understanding of WD40 proteins and their molecular mechanisms linked to genome stability and cell cycle progression in this review, thereby demonstrating their pervasiveness and importance in cellular networks. PMID:25653723

  18. Multifunctional Roles for the Protein Translocation Machinery in RNA Anchoring to the Endoplasmic Reticulum*

    PubMed Central

    Jagannathan, Sujatha; Hsu, Jack C.-C.; Reid, David W.; Chen, Qiang; Thompson, Will J.; Moseley, Arthur M.; Nicchitta, Christopher V.

    2014-01-01

    Signal sequence-encoding mRNAs undergo translation-dependent localization to the endoplasmic reticulum (ER) and at the ER are anchored via translation on Sec61-bound ribosomes. Recent investigations into the composition and membrane association characteristics of ER-associated mRNAs have, however, revealed both ribosome-dependent (indirect) and ribosome-independent (direct) modes of mRNA association with the ER. These findings raise important questions regarding our understanding of how mRNAs are selected, localized, and anchored to the ER. Using semi-intact tissue culture cells, we performed a polysome solubilization screen and identified conditions that distinguish polysomes engaged in the translation of distinct cohorts of mRNAs. To gain insight into the molecular basis of direct mRNA anchoring to the ER, we performed RNA-protein UV photocross-linking studies in rough microsomes and demonstrate that numerous ER integral membrane proteins display RNA binding activity. Quantitative proteomic analyses of HeLa cytosolic and ER-bound polysome fractions identified translocon components as selective polysome-interacting proteins. Notably, the Sec61 complex was highly enriched in polysomes engaged in the translation of endomembrane organelle proteins, whereas translocon accessory proteins, such as ribophorin I, were present in all subpopulations of ER-associated polysomes. Analyses of the protein composition of oligo(dT)-selected UV photocross-linked ER protein-RNA adducts identified Sec61α,β and ribophorin I as ER-poly(A) mRNA-binding proteins, suggesting unexpected roles for the protein translocation and modification machinery in mRNA anchoring to the ER. In summary, we propose that multiple mechanisms of mRNA and ribosome association with ER operate to enable an mRNA transcriptome-wide function for the ER in protein synthesis. PMID:25063809

  19. Expression of the multifunctional Y-box protein, YB-1, in myofibroblasts of the infarcted rat heart

    SciTech Connect

    Kamalov, German; Varma, Balwantkumar R.; Lu Li; Sun Yao; Weber, Karl T.; Guntaka, Ramareddy V. . E-mail: rguntaka@utmem.edu

    2005-08-19

    Intracellular signaling mechanisms regulating the turnover of {alpha}-SMA-positive myofibroblasts (myoFbs) at the site of myocardial infarction (MI) are poorly understood. Y-Box (YB)-1, a multifunctional protein, may be involved in regulation of proliferation, migration and apoptosis of myoFbs. Our objective was to study the expression of YB-1 in the infarcted rat heart and its localization in myoFbs. On days 3-28 following MI, we monitored YB-1 expression and its colocalization with {alpha}-SMA, and proliferation markers PCNA and Ki-67 in infarcted tissue by Western blot, immunohistochemistry, and immunofluorescent double-labeling. YB-1 is barely detectable in normal myocardium. At the infarct site, however, YB-1 is markedly elevated from day 3 post-MI concomitant with the induction of cell proliferation. MyoFbs are the major source of YB-1 and retain it up to day 28 post-MI. We suggest early expression of YB-1 promotes proliferation and migration of myoFbs, whereas prolonged expression may be responsible for scar formation.

  20. Multifunctionality of PIWI proteins in control of germline stem cell fate.

    PubMed

    Yakushev, E Y; Sokolova, O A; Gvozdev, V A; Klenov, M S

    2013-06-01

    PIWI proteins interacting with specific type of small RNAs (piRNAs) repress transposable elements in animals. Besides, they have been shown to participate in various cellular processes: in the regulation of heterochromatin formation including telomere structures, in the control of translation and the cell cycle, and in DNA rearrangements. PIWI proteins were first identified by their roles in the self-renewal of germline stem cells. PIWI protein functions are not limited to gonadogenesis, but the role in determining the fate of stem cells is their specific feature conserved throughout the evolution of animals. Molecular mechanisms underlying these processes are far from being understood. This review focuses on the role of PIWI proteins in the control of maintenance and proliferation of germinal stem cells and its relation to the known function of PIWI in transposon repression. PMID:23980885

  1. AminoxyTMT: A novel multi-functional reagent for characterization of protein carbonylation.

    PubMed

    Afiuni-Zadeh, Somaieh; Rogers, John C; Snovida, Sergei I; Bomgarden, Ryan D; Griffin, Timothy J

    2016-01-01

    Protein carbonylation is a common oxidative stress (OS)-driven post-translational modification (PTM). Proteome-wide carbonylation events can best be characterized using a combination of analytical approaches. Immunoblotting of carbonylated proteins provides data on the extent of modifications within complex samples, as well as a broad comparison of carbonylation profiles between different biological states (e.g., disease versus control), while mass spectrometry (MS)-based analysis provides information on proteins susceptible to carbonylation, as well as the potential for quantitative characterization of specific sites of amino acid modification. Here, we present a novel use for aminoxyTMT, a derivative of the Tandem Mass Tag (TMT) isobaric labeling reagent, which utilizes an aminooxy functional group for covalent labeling of reactive carbonyls in proteins. When coupled with anti-TMT antibody, we demonstrate the use of aminoxyTMT for immunoblot profiling of protein carbonylation in complex mixtures, as well as enrichment of modified peptides from these mixtures. Proof-of-principle experiments also show the amenability of aminoxyTMT-labeled carbonylated peptides enriched from complex mixtures to identification using tandem MS (MS/MS) and database searching, as well as quantitative analysis using TMT-based reporter ion intensity measurements. PMID:27071607

  2. Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein

    SciTech Connect

    Calvo, Eric; Mans, Ben J.; Ribeiro, José M.C.; Andersen, John F.

    2009-04-07

    The mosquito D7 salivary proteins are encoded by a multigene family related to the arthropod odorant-binding protein (OBP) superfamily. Forms having either one or two OBP domains are found in mosquito saliva. Four single-domain and one two-domain D7 proteins from Anopheles gambiae and Aedes aegypti (AeD7), respectively, were shown to bind biogenic amines with high affinity and with a stoichiometry of one ligand per protein molecule. Sequence comparisons indicated that only the C-terminal domain of AeD7 is homologous to the single-domain proteins from A. gambiae, suggesting that the N-terminal domain may bind a different class of ligands. Here, we describe the 3D structure of AeD7 and examine the ligand-binding characteristics of the N- and C-terminal domains. Isothermal titration calorimetry and ligand complex crystal structures show that the N-terminal domain binds cysteinyl leukotrienes (cysLTs) with high affinities (50-60 nM) whereas the C-terminal domain binds biogenic amines. The lipid chain of the cysLT binds in a hydrophobic pocket of the N-terminal domain, whereas binding of norepinephrine leads to an ordering of the C-terminal portion of the C-terminal domain into an alpha-helix that, along with rotations of Arg-176 and Glu-268 side chains, acts to bury the bound ligand.

  3. Multifunctional Delivery Systems for Advanced oral Uptake of Peptide/Protein Drugs.

    PubMed

    Park, Jin Woo; Kim, Sun Jin; Kwag, Dong Sup; Kim, Sol; Park, Jeyoung; Youn, Yu Seok; Bae, You Han; Lee, Eun Seong

    2015-01-01

    In recent years, advances in biotechnology and protein engineering have enabled the production of large quantities of proteins and peptides as important therapeutic agents. Various researchers have used biocompatible functional polymers to prepare oral dosage forms of proteins and peptides for chronic use and for easier administration to enhance patient compliance. However, there is a need to enhance their safety and effectiveness further. Most macromolecules undergo severe denaturation at low pH and enzymatic degradation in the gastrointestinal tract. The macromolecules' large molecular size and low lipophilicity cause low permeation through the intestinal membrane. The major strategies that have been used to overcome these challenges (in oral drug carrier systems) can be classified as follows: enteric coating or encapsulation with pH-sensitive polymers or mucoadhesive polymers, co-administration of protease inhibitors, incorporation of absorption enhancers, modification of the physicochemical properties of the macromolecules, and site-specific delivery to the colon. This review attempts to summarize the various advanced oral delivery carriers, including nanoparticles, lipid carriers, such as liposomes, nano-aggregates using amphiphilic polymers, complex coacervation of oppositely charged polyelectrolytes, and inorganic porous particles. The particles were formulated and/or surface modified with functional polysaccharides or synthetic polymers to improve oral bioavailability of proteins and peptides. We also discuss formulation strategies to overcome barriers, therapeutic efficacies in vivo, and potential benefits and issues for successful oral dosage forms of the proteins and peptides. PMID:26027575

  4. Isolation and characterization of the orotidine 5'-monophosphate decarboxylase domain of the multifunctional protein uridine 5'-monophosphate synthase.

    PubMed

    Floyd, E E; Jones, M E

    1985-08-01

    The multifunctional protein uridine 5'-monophosphate (UMP) synthase catalyzes the final two reactions of the de novo biosynthesis of UMP in mammalian cells by the sequential action of orotate phosphoribosyltransferase (EC 2.4.2.10) and orotidine 5'-monophosphate (OMP) decarboxylase (EC 4.1.1.23). This protein is composed of one or two identical subunits; the monomer weighs of 51,500 daltons. UMP synthase from mouse Ehrlich ascites cells can exist as three distinct species as determined by sucrose density gradient centrifugation: a 3.6 S monomer, a 5.1 S dimer, and a 5.6 S conformationally altered dimer. Limited digestion of each of these three species with trypsin produced a 28,500-dalton peptide that was relatively resistant to further proteolysis. The peptide appears to be one of the two enzyme domains of UMP synthase for it retained only OMP decarboxylase activity. Similar results were obtained when UMP synthase was digested with elastase. OMP decarboxylase activity was less stable for the domain than for UMP synthase; the domain can rapidly lose activity upon storage or upon dilution. The size of the mammalian OMP decarboxylase domain is similar to that of yeast OMP decarboxylase. If the polypeptides which are cleaved from UMP synthase by trypsin are derived exclusively from either the amino or the carboxyl end of UMP synthase, then the size of a fragment possessing the orotate phosphoribosyltransferase domain could be as large as 23,000 daltons which is similar in size to the orotate phosphoribosyltransferase of yeast and of Escherichia coli. PMID:3839509

  5. Peroxisomal multifunctional protein-2 deficiency causes neuroinflammation and degeneration of Purkinje cells independent of very long chain fatty acid accumulation.

    PubMed

    Verheijden, Simon; Bottelbergs, Astrid; Krysko, Olga; Krysko, Dmitri V; Beckers, Lien; De Munter, Stephanie; Van Veldhoven, Paul P; Wyns, Sabine; Kulik, Wim; Nave, Klaus-Armin; Ramer, Matt S; Carmeliet, Peter; Kassmann, Celia M; Baes, Myriam

    2013-10-01

    Although peroxisome biogenesis and β-oxidation disorders are well known for their neurodevelopmental defects, patients with these disorders are increasingly diagnosed with neurodegenerative pathologies. In order to investigate the cellular mechanisms of neurodegeneration in these patients, we developed a mouse model lacking multifunctional protein 2 (MFP2, also called D-bifunctional protein), a central enzyme of peroxisomal β-oxidation, in all neural cells (Nestin-Mfp2(-/-)) or in oligodendrocytes (Cnp-Mfp2(-/-)) and compared these models with an already established general Mfp2 knockout. Nestin-Mfp2 but not Cnp-Mfp2 knockout mice develop motor disabilities and ataxia, similar to the general mutant. Deterioration of motor performance correlates with the demise of Purkinje cell axons in the cerebellum, which precedes loss of Purkinje cells and cerebellar atrophy. This closely mimics spinocerebellar ataxias of patients affected with mild peroxisome β-oxidation disorders. However, general knockouts have a much shorter life span than Nestin-Mfp2 knockouts which is paralleled by a disparity in activation of the innate immune system. Whereas in general mutants a strong and chronic proinflammatory reaction proceeds throughout the brain, elimination of MFP2 from neural cells results in minor neuroinflammation. Neither the extent of the inflammatory reaction nor the cerebellar degeneration could be correlated with levels of very long chain fatty acids, substrates of peroxisomal β-oxidation. In conclusion, MFP2 has multiple tasks in the adult brain, including the maintenance of Purkinje cells and the prevention of neuroinflammation but this is not mediated by its activity in oligodendrocytes nor by its role in very long chain fatty acid degradation. PMID:23777740

  6. Polarized Defense Against Fungal Pathogens Is Mediated by the Jacalin-Related Lectin Domain of Modular Poaceae-Specific Proteins.

    PubMed

    Weidenbach, Denise; Esch, Lara; Möller, Claudia; Hensel, Goetz; Kumlehn, Jochen; Höfle, Caroline; Hückelhoven, Ralph; Schaffrath, Ulrich

    2016-04-01

    Modular proteins are an evolutionary answer to optimize performance of proteins that physically interact with each other for functionality. Using a combination of genetic and biochemical experiments, we characterized the rice protein OsJAC1, which consists of a jacalin-related lectin (JRL) domain predicted to bind mannose-containing oligosaccharides, and a dirigent domain which might function in stereoselective coupling of monolignols. Transgenic overexpression of OsJAC1 in rice resulted in quantitative broad-spectrum resistance against different pathogens including bacteria, oomycetes, and fungi. Overexpression of this gene or its wheat ortholog TAJA1 in barley enhanced resistance against the powdery mildew fungus. Both protein domains of OsJAC1 are required to establish resistance as indicated by single or combined transient expression of individual domains. Expression of artificially separated and fluorescence-tagged protein domains showed that the JRL domain is sufficient for targeting the powdery mildew penetration site. Nevertheless, co-localization of the lectin and the dirigent domain occurred. Phylogenetic analyses revealed orthologs of OsJAC1 exclusively within the Poaceae plant family. Dicots, by contrast, only contain proteins with either JRL or dirigent domain(s). Altogether, our results identify OsJAC1 as a representative of a novel type of resistance protein derived from a plant lineage-specific gene fusion event for better function in local pathogen defense. PMID:26708413

  7. phiX174 cistron A protein is a multifunctional enzyme in DNA replication.

    PubMed

    Eisenberg, S; Griffith, J; Kornberg, A

    1977-08-01

    The cistron A protein induced by phage varphiX174 nicks (produces a single-strand break in) the viral strand of the superhelical varphiX duplex DNA, thereby forming a complex with the DNA. The protein, seen bound to the DNA in the electron microscope, was located in the restriction endonuclease fragment between nucleotides 4290 and 4330 on the varphiX map [Sanger, F., Air, G. M., Barrel, B. G., Brown, N. L., Coulson, A. R., Fiddes, J. C., Hutchison, C. A., III, Slocomb, P. M. Y. & Smith, M. (1977) Nature 265, 687-695]. Replication also was initiated at this point, thus identifying the site of cistron A protein nicking and binding as the origin of replication. The cisA-DNA complex (separated from free cistron A protein), upon the addition of Escherichia coli rep protein, ATP, and DNA binding protein, is unwound to generate a single-stranded linear [presumably the nicked (+) strand] and a circular [presumably the (-) strand] molecule. The cisA-DNA complex, upon the further addition of DNA polymerase III holoenzyme and deoxynucleoside triphosphates, supports replication to generate viral, single-stranded circles, as many as 15 circles per cisA-DNA complex. The replicating intermediates seen in the electron microscope are a novel form of "rolling circle" [Gilbert, W. & Dressler, D. H. (1969) Cold Spring Harbor Symp. Quant. Biol. 33, 473-485]. The 5' end (presumably with the cistron A protein bound to it) is locked in the replication fork and loops back to accompany the strand-separation and replication fork around the template [(-) strand] circle. Thus, the multiple functions of cistron A protein include: (i) nicking the viral strand at the origin of replication to initiate a round of replication, (ii) participating in a complex which supports fork movement in strand separation and replication, (iii) nicking again at the regenerated origin to produce a unit-length DNA, and (iv) ligating the newly generated 3'-OH end to the 5'-phosphate-complexed end to form a circular

  8. Frequency of Factor H-binding Protein Modular Groups and Susceptibility to Cross-reactive Bactericidal Activity in Invasive Meningococcal Isolates

    PubMed Central

    Pajon, Rolando; Beernink, Peter T.; Harrison, Lee H.; Granoff, Dan M.

    2010-01-01

    Meningococcal factor H binding protein (fHbp) is a promising vaccine candidate that elicits serum bactericidal antibodies in humans. Based on sequence variability of the entire protein, fHbp has been divided into three variant groups or two sub-families. We recently reported that the fHbp architecture was modular, consisting of five variable segments, each encoded by genes from one of two lineages. Based on combinations of segments from different lineages, all 70 known fHbp sequence variants could be classified into one of six modular groups. In this study, we analyzed sequences of 172 new fHbp variants that were available from public databases. All but three variants could be classified into one of the six previously described modular groups. Among systematically collected invasive group B isolates from the U.S. and Europe, modular group I overall was most common (60%) but group IV (natural chimeras) accounted for 23% of UK isolates and <1% of U.S. isolates (P<0.0001). Mouse antisera to recombinant fHbp from each of the modular groups showed modular group-specific bactericidal activity against strains with low fHbp expression but had broader activity against strains with higher fHbp expression. Thus both modular group and relative expression of fHbp affected strain susceptibility to anti-fHbp bactericidal activity. The results confirmed the modular architecture of fHbp and underscored its importance for the design of broadly protective group B vaccines in different regions. PMID:20044056

  9. The antagonistic effect of Banana bunchy top virus multifunctional protein B4 against Fusarium oxysporum.

    PubMed

    Zhuang, Jun; Coates, Christopher J; Mao, Qianzhuo; Wu, Zujian; Xie, Lianhui

    2016-06-01

    The viral-induced banana bunchy top disease and the fungal-induced banana blight are two major causes of concern for industrial scale production of bananas. Banana blight is particularly troublesome, affecting ∼80% of crops worldwide. Strict guidelines and protocols are in place in order to ameliorate the effects of this devastating disease, yet little success has been achieved. From the data presented here, we have found that Banana bunchy top virus (BBTV)-infected bananas are more resistant to Fusarium oxysporum f. sp. cubense (Foc). BBTV appears to be antagonistic towards Foc, thus improving the survivability of plants against blight. The BBTV suppressor of RNA silencing, namely protein B4, displays fungicidal properties in vitro. Furthermore, transgenic tomatoes expressing green fluorescent protein (GFP)-tagged protein B4 demonstrate enhanced resistance to F. oxysporum f. sp. lycopersici (Fol). Differential gene expression analysis indicates that increased numbers of photogenesis-related gene transcripts are present in dark-green leaves of B4-GFP-modified tomato plants relative to those found in WT plants. Conversely, the transcript abundance of immunity-related genes is substantially lower in transgenic tomatoes compared with WT plants, suggesting that plant defences may be influenced by protein B4. This viral-fungal interaction provides new insights into microbial community dynamics within a single host and has potential commercial value for the breeding of transgenic resistance to Fusarium-related blight/wilt. PMID:26369403

  10. Nuclear Import and the Evolution of a Multifunctional RNA-binding Protein

    PubMed Central

    Rosenblum, Jonathan S.; Pemberton, Lucy F.; Bonifaci, Neris; Blobel, Günter

    1998-01-01

    La (SS-B) is a highly expressed protein that is able to bind 3′-oligouridylate and other common RNA sequence/structural motifs. By virtue of these interactions, La is present in a myriad of nuclear and cytoplasmic ribonucleoprotein complexes in vivo where it may function as an RNA-folding protein or RNA chaperone. We have recently characterized the nuclear import pathway of the S. cerevisiae La, Lhp1p. The soluble transport factor, or karyopherin, that mediates the import of Lhp1p is Kap108p/Sxm1p. We have now determined a 113-amino acid domain of Lhp1p that is brought to the nucleus by Kap108p. Unexpectedly, this domain does not coincide with the previously identified nuclear localization signal of human La. Furthermore, when expressed in Saccharomyces cerevisiae, the nuclear localization of Schizosaccharomyces pombe, Drosophila, and human La proteins are independent of Kap108p. We have been able to reconstitute the nuclear import of human La into permeabilized HeLa cells using the recombinant human factors karyopherin α2, karyopherin β1, Ran, and p10. As such, the yeast and human La proteins are imported using different sequence motifs and dissimilar karyopherins. Our results are consistent with an intermingling of the nuclear import and evolution of La. PMID:9817748

  11. Multifunctional nanoparticle-protein conjugates with controllable bioactivity and pH responsiveness

    NASA Astrophysics Data System (ADS)

    Liu, Feng; Xue, Lulu; Yuan, Yuqi; Pan, Jingjing; Zhang, Chenjie; Wang, Hongwei; Brash, John L.; Yuan, Lin; Chen, Hong

    2016-02-01

    The modulation of protein activity is of significance for disease therapy, molecular diagnostics, and tissue engineering. Nanoparticles offer a new platform for the preparation of protein conjugates with improved protein properties. In the present work, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase) and poly(methacrylic acid) (PMAA) were attached together to gold nanoparticles (AuNPs), forming AuNP-PPase-PMAA conjugates having controllable multi-biofunctionalities and responsiveness to pH. By treating with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and regulating the pH, the bioactivity of the conjugate becomes ``on/off''-switchable. In addition, by taking advantage of the ability of AuNPs to undergo reversible aggregation/dispersion, the conjugates can be recycled and reused multiple times; and due to the shielding effect of the PMAA, the conjugated enzyme has high resistance to protease digestion. This approach has considerable potential in areas such as controlled delivery and release of drugs, biosensing, and biocatalysis.The modulation of protein activity is of significance for disease therapy, molecular diagnostics, and tissue engineering. Nanoparticles offer a new platform for the preparation of protein conjugates with improved protein properties. In the present work, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase) and poly(methacrylic acid) (PMAA) were attached together to gold nanoparticles (AuNPs), forming AuNP-PPase-PMAA conjugates having controllable multi-biofunctionalities and responsiveness to pH. By treating with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and regulating the pH, the bioactivity of the conjugate becomes ``on/off''-switchable. In addition, by taking advantage of the ability of AuNPs to undergo reversible aggregation/dispersion, the conjugates can be recycled and reused multiple times; and due to the shielding effect of the PMAA, the conjugated enzyme has high resistance to protease digestion

  12. Secretory leukocyte protease inhibitor (SLPI), a multifunctional protein in the host defense response.

    PubMed

    Majchrzak-Gorecka, Monika; Majewski, Pawel; Grygier, Beata; Murzyn, Krzysztof; Cichy, Joanna

    2016-04-01

    Secretory leukocyte protease inhibitor (SLPI), a ∼12kDa nonglycosylated cationic protein, is emerging as an important regulator of innate and adaptive immunity and as a component of tissue regenerative programs. First described as an inhibitor of serine proteases such as neutrophil elastase, this protein is increasingly recognized as a molecule that benefits the host via its anti-proteolytic, anti-microbial and immunomodulatory activities. Here, we discuss the diverse functions of SLPI. Moreover, we review several novel layers of SLPI-mediated control that protect the host from excessive/dysregulated inflammation typical of infectious, allergic and autoinflammatory diseases and that support healing responses through affecting cell proliferation, differentiation and apoptosis. PMID:26718149

  13. Targeting multifunctional proteins by virtual screening: structurally diverse cytohesin inhibitors with differentiated biological functions.

    PubMed

    Stumpfe, Dagmar; Bill, Anke; Novak, Nina; Loch, Gerrit; Blockus, Heike; Geppert, Hanna; Becker, Thomas; Schmitz, Anton; Hoch, Michael; Kolanus, Waldemar; Famulok, Michael; Bajorath, Jürgen

    2010-09-17

    Virtual screening (VS) of chemical libraries formatted in silico provides an alternative to experimental high-throughput screening (HTS) for the identification of small molecule modulators of protein function. We have tailored a VS approach combining fingerprint similarity searching and support vector machine modeling toward the identification of small molecular probes for the study of cytohesins, a family of cytoplasmic regulator proteins with multiple cellular functions. A total of 40 new structurally diverse inhibitors were identified, and 26 of these compounds were more active than the primary VS template, a single known inhibitory chemotype, in at least one of three different assays (guanine nucleotide exchange, Drosophila insulin signaling, and human leukocyte cell adhesion). Moreover, these inhibitors displayed differential inhibitory profiles. Our findings demonstrate that, at least for the cytohesins, computational extrapolation from known active compounds was capable of identifying small molecular probes with highly diversified functional profiles. PMID:20614894

  14. Calcium/calmodulin-dependent protein kinase IV: A multifunctional enzyme and potential therapeutic target.

    PubMed

    Naz, Huma; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2016-05-01

    The calcium/calmodulin-dependent protein kinase IV (CAMKIV) belongs to the serine/threonine protein kinase family, and is primarily involved in transcriptional regulation in lymphocytes, neurons and male germ cells. CAMKIV operates the signaling cascade and regulates activity of several transcription activators by phosphorylation, which in turn plays pivotal roles in immune response, inflammation and memory consolidation. In this review, we tried to focus on different aspects of CAMKIV to understand the significance of this protein in the biological system. This enzyme is associated with varieties of disorders such as cerebral hypoxia, azoospermia, endometrial and ovarian cancer, systemic lupus, etc., and hence it is considered as a potential therapeutic target. Structure of CAMKIV is comprised of five distinct domains in which kinase domain is responsible for enzyme activity. CAMKIV is involved in varieties of cellular functions such as regulation of gene expression, T-cell maturation, regulation of survival phase of dendritic cells, bone growth and metabolism, memory consolidation, sperm motility, regulation of microtubule dynamics, cell-cycle progression and apoptosis. In this review, we performed an extensive analysis on structure, function and regulation of CAMKIV and associated diseases. PMID:26773169

  15. Multifunctional nanoparticle-protein conjugates with controllable bioactivity and pH responsiveness.

    PubMed

    Liu, Feng; Xue, Lulu; Yuan, Yuqi; Pan, Jingjing; Zhang, Chenjie; Wang, Hongwei; Brash, John L; Yuan, Lin; Chen, Hong

    2016-02-21

    The modulation of protein activity is of significance for disease therapy, molecular diagnostics, and tissue engineering. Nanoparticles offer a new platform for the preparation of protein conjugates with improved protein properties. In the present work, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase) and poly(methacrylic acid) (PMAA) were attached together to gold nanoparticles (AuNPs), forming AuNP-PPase-PMAA conjugates having controllable multi-biofunctionalities and responsiveness to pH. By treating with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and regulating the pH, the bioactivity of the conjugate becomes "on/off"-switchable. In addition, by taking advantage of the ability of AuNPs to undergo reversible aggregation/dispersion, the conjugates can be recycled and reused multiple times; and due to the shielding effect of the PMAA, the conjugated enzyme has high resistance to protease digestion. This approach has considerable potential in areas such as controlled delivery and release of drugs, biosensing, and biocatalysis. PMID:26840617

  16. Multifunctional role of the Pitx2 homeodomain protein C-terminal tail.

    PubMed

    Amendt, B A; Sutherland, L B; Russo, A F

    1999-10-01

    Pitx2 is a newly described bicoid-like homeodomain transcription factor that is defective in Rieger syndrome and shows a striking leftward developmental asymmetry. We have previously shown that Pitx2 (also called Ptx2 and RIEG) transactivates a reporter gene containing a bicoid enhancer and synergistically transactivates the prolactin promoter in the presence of the POU homeodomain protein Pit-1. In this report, we focused on the C-terminal region which is mutated in some Rieger patients and contains a highly conserved 14-amino-acid element. Deletion analysis of Pitx2 revealed that the C-terminal 39-amino-acid tail represses DNA binding activity and is required for Pitx2-Pit-1 interaction and Pit-1 synergism. Pit-1 interaction with the Pitx2 C terminus masks the inhibitory effect and promotes increased DNA binding activity. Interestingly, cotransfection of an expression vector encoding the C-terminal 39 amino acids of Pitx2 specifically inhibits Pitx2 transactivation activity. In contrast, the C-terminal 39-amino-acid peptide interacts with Pitx2 to increase its DNA binding activity. These data suggest that the C-terminal tail intrinsically inhibits the Pitx2 protein and that this inhibition can be overcome by interaction with other transcription factors to allow activation during development. PMID:10490637

  17. Multifunctional Role of the Pitx2 Homeodomain Protein C-Terminal Tail

    PubMed Central

    Amendt, Brad A.; Sutherland, Lillian B.; Russo, Andrew F.

    1999-01-01

    Pitx2 is a newly described bicoid-like homeodomain transcription factor that is defective in Rieger syndrome and shows a striking leftward developmental asymmetry. We have previously shown that Pitx2 (also called Ptx2 and RIEG) transactivates a reporter gene containing a bicoid enhancer and synergistically transactivates the prolactin promoter in the presence of the POU homeodomain protein Pit-1. In this report, we focused on the C-terminal region which is mutated in some Rieger patients and contains a highly conserved 14-amino-acid element. Deletion analysis of Pitx2 revealed that the C-terminal 39-amino-acid tail represses DNA binding activity and is required for Pitx2-Pit-1 interaction and Pit-1 synergism. Pit-1 interaction with the Pitx2 C terminus masks the inhibitory effect and promotes increased DNA binding activity. Interestingly, cotransfection of an expression vector encoding the C-terminal 39 amino acids of Pitx2 specifically inhibits Pitx2 transactivation activity. In contrast, the C-terminal 39-amino-acid peptide interacts with Pitx2 to increase its DNA binding activity. These data suggest that the C-terminal tail intrinsically inhibits the Pitx2 protein and that this inhibition can be overcome by interaction with other transcription factors to allow activation during development. PMID:10490637

  18. The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

    PubMed Central

    Jain, Kirti; Basu, Alakananda

    2014-01-01

    The protein kinase C (PKC) family proteins are important signal transducers and have long been the focus of cancer research. PKCɛ, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCɛ. While earlier research established the survival functions of PKCɛ, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCɛ has also been implicated in epithelial to mesenchymal transition (EMT), which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCɛ affects cell-extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCɛ signaling to cancer stem cell functioning. This review focuses on the role of PKCɛ in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCɛ as a target for cancer therapy. PMID:24727247

  19. Initiating protease with modular domains interacts with β-glucan recognition protein to trigger innate immune response in insects

    PubMed Central

    Takahashi, Daisuke; Garcia, Brandon L.; Kanost, Michael R.

    2015-01-01

    The autoactivation of an initiating serine protease upon binding of pattern recognition proteins to pathogen surfaces is a crucial step in eliciting insect immune responses such as the activation of Toll and prophenoloxidase pathways. However, the molecular mechanisms responsible for autoactivation of the initiating protease remains poorly understood. Here, we investigated the molecular basis for the autoactivation of hemolymph protease 14 (HP14), an initiating protease in hemolymph of Manduca sexta, upon the binding of β-1,3-glucan by its recognition protein, βGRP2. Biochemical analysis using HP14 zymogen (proHP14), βGRP2, and the recombinant proteins as truncated forms showed that the amino-terminal modular low-density lipoprotein receptor class A (LA) domains within HP14 are required for proHP14 autoactivation that is stimulated by its interaction with βGRP2. Consistent with this result, recombinant LA domains inhibit the activation of proHP14 and prophenoloxidase, likely by competing with the interaction between βGRP2 and LA domains within proHP14. Using surface plasmon resonance, we demonstrated that immobilized LA domains directly interact with βGRP2 in a calcium-dependent manner and that high-affinity interaction requires the C-terminal glucanase-like domain of βGRP2. Importantly, the affinity of LA domains for βGRP2 increases nearly 100-fold in the presence of β-1,3-glucan. Taken together, these results present the first experimental evidence to our knowledge that LA domains of an insect modular protease and glucanase-like domains of a βGRP mediate their interaction, and that this binding is essential for the protease autoactivation. Thus, our study provides important insight into the molecular basis underlying the initiation of protease cascade in insect immune responses. PMID:26504233

  20. WSTF does it all: a multifunctional protein in transcription, repair and replication

    PubMed Central

    Barnett, Chris; Krebs, Jocelyn E.

    2011-01-01

    Williams Syndrome Transcription Factor (WSTF) has emerged as an incredibly versatile nuclear protein. WSTF and the ATP-dependent chromatin remodeling complexes in which it exists, WINAC, WICH and B-WICH have been studied in a variety of organisms. This research has revealed roles for WSTF in a number of diverse molecular events. WSTF function includes chromatin assembly, Pol I and III gene regulation, vitamin D metabolism and DNA repair. In addition to functioning as a subunit of several ATP-dependent chromatin remodeling complexes, WSTF binds specifically to acetylated histones and is itself a histone kinase, as well as a target of phosphorylation. This review will describe the three known WSTF-containing complexes and discuss their various roles as well as mechanisms of regulating WSTF activity. PMID:21326359

  1. Multifunctional roles of insulin-like growth factor binding protein 5 in breast cancer

    PubMed Central

    Akkiprik, Mustafa; Feng, Yumei; Wang, Huamin; Chen, Kexin; Hu, Limei; Sahin, Aysegul; Krishnamurthy, Savitri; Ozer, Ayse; Hao, Xishan; Zhang, Wei

    2008-01-01

    The insulin-like growth factor axis, which has been shown to protect cells from apoptosis, plays an essential role in normal cell physiology and in cancer development. The family of insulin-like growth factor binding proteins (IGFBPs) has been shown to have a diverse spectrum of functions in cell growth, death, motility, and tissue remodeling. Among the six IGFBP family members, IGFBP-5 has recently been shown to play an important role in the biology of breast cancer, especially in breast cancer metastasis; however, the exact mechanisms of action remain obscure and sometimes paradoxical. An in-depth understanding of IGFBP-5 would shed light on its potential role as a target for breast cancer therapeutics. PMID:18710598

  2. Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

    PubMed Central

    Vannucci, Luca; Falvo, Elisabetta; Fornara, Manuela; Di Micco, Patrizio; Benada, Oldrich; Krizan, Jiri; Svoboda, Jan; Hulikova-Capkova, Katarina; Morea, Veronica; Boffi, Alberto; Ceci, Pierpaolo

    2012-01-01

    Background Nanoparticle-based systems are promising for the development of imaging and therapeutic agents. The main advantage of nanoparticles over traditional systems lies in the possibility of loading multiple functionalities onto a single molecule, which are useful for therapeutic and/or diagnostic purposes. These functionalities include targeting moieties which are able to recognize receptors overexpressed by specific cells and tissues. However, targeted delivery of nanoparticles requires an accurate system design. We present here a rationally designed, genetically engineered, and chemically modified protein-based nanoplatform for cell/tissue-specific targeting. Methods Our nanoparticle constructs were based on the heavy chain of the human protein ferritin (HFt), a highly symmetrical assembly of 24 subunits enclosing a hollow cavity. HFt-based nanoparticles were produced using both genetic engineering and chemical functionalization methods to impart several functionalities, ie, the α-melanocyte-stimulating hormone peptide as a melanoma-targeting moiety, stabilizing and HFt-masking polyethylene glycol molecules, rhodamine fluorophores, and magnetic resonance imaging agents. The constructs produced were extensively characterized by a number of physicochemical techniques, and assayed for selective melanoma-targeting in vitro and in vivo. Results Our HFt-based nanoparticle constructs functionalized with the α-melanocyte-stimulating hormone peptide moiety and polyethylene glycol molecules were specifically taken up by melanoma cells but not by other cancer cell types in vitro. Moreover, experiments in melanoma-bearing mice indicate that these constructs have an excellent tumor-targeting profile and a long circulation time in vivo. Conclusion By masking human HFt with polyethylene glycol and targeting it with an α-melanocyte-stimulating hormone peptide, we developed an HFt-based melanoma-targeting nanoplatform for application in melanoma diagnosis and treatment

  3. The Bacteroides sp. 3_1_23 Pif1 protein is a multifunctional helicase.

    PubMed

    Liu, Na-Nv; Duan, Xiao-Lei; Ai, Xia; Yang, Yan-Tao; Li, Ming; Dou, Shuo-Xing; Rety, Stephane; Deprez, Eric; Xi, Xu-Guang

    2015-10-15

    ScPif1 DNA helicase is the prototypical member of a 5'-to-3' helicase superfamily conserved from bacteria to human and plays various roles in the maintenance of genomic homeostasis. While many studies have been performed with eukaryotic Pif1 helicases, including yeast and human Pif1 proteins, the potential functions and biochemical properties of prokaryotic Pif1 helicases remain largely unknown. Here, we report the expression, purification and biochemical analysis of Pif1 helicase from Bacteroides sp. 3_1_23 (BsPif1). BsPif1 binds to a large panel of DNA substrates and, in particular, efficiently unwinds partial duplex DNAs with 5'-overhang, fork-like substrates, D-loop and flap-like substrates, suggesting that BsPif1 may act at stalled DNA replication forks and enhance Okazaki fragment maturation. Like its eukaryotic homologues, BsPif1 resolves R-loop structures and unwinds DNA-RNA hybrids. Furthermore, BsPif1 efficiently unfolds G-quadruplexes and disrupts nucleoprotein complexes. Altogether, these results highlight that prokaryotic Pif1 helicases may resolve common issues that arise during DNA transactions. Interestingly, we found that BsPif1 is different from yeast Pif1, but resembles more human Pif1 with regard to substrate specificity, helicase activity and mode of action. These findings are discussed in the context of the possible functions of prokaryotic Pif1 helicases in vivo. PMID:26384418

  4. The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis

    PubMed Central

    Jette, Nicholas; Lees-Miller, Susan P.

    2015-01-01

    The DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and the Ku70/80 heterodimer. Over the past two decades, significant progress has been made in elucidating the role of DNA-PK in non-homologous end joining (NHEJ), the major pathway for repair of ionizing radiation-induced DNA double strand breaks in human cells and recently, additional roles for DNA-PK have been reported. In this review, we will describe the biochemistry, structure and function of DNA-PK, its roles in DNA double strand break repair and its newly described roles in mitosis and other cellular processes. PMID:25550082

  5. CASP11 - An Evaluation of a Modular BCL::Fold-Based Protein Structure Prediction Pipeline.

    PubMed

    Fischer, Axel W; Heinze, Sten; Putnam, Daniel K; Li, Bian; Pino, James C; Xia, Yan; Lopez, Carlos F; Meiler, Jens

    2016-01-01

    In silico prediction of a protein's tertiary structure remains an unsolved problem. The community-wide Critical Assessment of Protein Structure Prediction (CASP) experiment provides a double-blind study to evaluate improvements in protein structure prediction algorithms. We developed a protein structure prediction pipeline employing a three-stage approach, consisting of low-resolution topology search, high-resolution refinement, and molecular dynamics simulation to predict the tertiary structure of proteins from the primary structure alone or including distance restraints either from predicted residue-residue contacts, nuclear magnetic resonance (NMR) nuclear overhauser effect (NOE) experiments, or mass spectroscopy (MS) cross-linking (XL) data. The protein structure prediction pipeline was evaluated in the CASP11 experiment on twenty regular protein targets as well as thirty-three 'assisted' protein targets, which also had distance restraints available. Although the low-resolution topology search module was able to sample models with a global distance test total score (GDT_TS) value greater than 30% for twelve out of twenty proteins, frequently it was not possible to select the most accurate models for refinement, resulting in a general decay of model quality over the course of the prediction pipeline. In this study, we provide a detailed overall analysis, study one target protein in more detail as it travels through the protein structure prediction pipeline, and evaluate the impact of limited experimental data. PMID:27046050

  6. CASP11 – An Evaluation of a Modular BCL::Fold-Based Protein Structure Prediction Pipeline

    PubMed Central

    Fischer, Axel W.; Heinze, Sten; Putnam, Daniel K.; Li, Bian; Pino, James C.; Xia, Yan; Lopez, Carlos F.; Meiler, Jens

    2016-01-01

    In silico prediction of a protein’s tertiary structure remains an unsolved problem. The community-wide Critical Assessment of Protein Structure Prediction (CASP) experiment provides a double-blind study to evaluate improvements in protein structure prediction algorithms. We developed a protein structure prediction pipeline employing a three-stage approach, consisting of low-resolution topology search, high-resolution refinement, and molecular dynamics simulation to predict the tertiary structure of proteins from the primary structure alone or including distance restraints either from predicted residue-residue contacts, nuclear magnetic resonance (NMR) nuclear overhauser effect (NOE) experiments, or mass spectroscopy (MS) cross-linking (XL) data. The protein structure prediction pipeline was evaluated in the CASP11 experiment on twenty regular protein targets as well as thirty-three ‘assisted’ protein targets, which also had distance restraints available. Although the low-resolution topology search module was able to sample models with a global distance test total score (GDT_TS) value greater than 30% for twelve out of twenty proteins, frequently it was not possible to select the most accurate models for refinement, resulting in a general decay of model quality over the course of the prediction pipeline. In this study, we provide a detailed overall analysis, study one target protein in more detail as it travels through the protein structure prediction pipeline, and evaluate the impact of limited experimental data. PMID:27046050

  7. SINEUPs are modular antisense long non-coding RNAs that increase synthesis of target proteins in cells

    PubMed Central

    Zucchelli, Silvia; Fasolo, Francesca; Russo, Roberta; Cimatti, Laura; Patrucco, Laura; Takahashi, Hazuki; Jones, Michael H.; Santoro, Claudio; Sblattero, Daniele; Cotella, Diego; Persichetti, Francesca; Carninci, Piero; Gustincich, Stefano

    2015-01-01

    Despite recent efforts in discovering novel long non-coding RNAs (lncRNAs) and unveiling their functions in a wide range of biological processes their applications as biotechnological or therapeutic tools are still at their infancy. We have recently shown that AS Uchl1, a natural lncRNA antisense to the Parkinson's disease-associated gene Ubiquitin carboxyl-terminal esterase L1 (Uchl1), is able to increase UchL1 protein synthesis at post-transcriptional level. Its activity requires two RNA elements: an embedded inverted SINEB2 sequence to increase translation and the overlapping region to target its sense mRNA. This functional organization is shared with several mouse lncRNAs antisense to protein coding genes. The potential use of AS Uchl1-derived lncRNAs as enhancers of target mRNA translation remains unexplored. Here we define AS Uchl1 as the representative member of a new functional class of natural and synthetic antisense lncRNAs that activate translation. We named this class of RNAs SINEUPs for their requirement of the inverted SINEB2 sequence to UP-regulate translation in a gene-specific manner. The overlapping region is indicated as the Binding Doman (BD) while the embedded inverted SINEB2 element is the Effector Domain (ED). By swapping BD, synthetic SINEUPs are designed targeting mRNAs of interest. SINEUPs function in an array of cell lines and can be efficiently directed toward N-terminally tagged proteins. Their biological activity is retained in a miniaturized version within the range of small RNAs length. Its modular structure was exploited to successfully design synthetic SINEUPs targeting endogenous Parkinson's disease-associated DJ-1 and proved to be active in different neuronal cell lines. In summary, SINEUPs represent the first scalable tool to increase synthesis of proteins of interest. We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies. PMID:26029048

  8. Spider wrapping silk fibre architecture arising from its modular soluble protein precursor.

    PubMed

    Tremblay, Marie-Laurence; Xu, Lingling; Lefèvre, Thierry; Sarker, Muzaddid; Orrell, Kathleen E; Leclerc, Jérémie; Meng, Qing; Pézolet, Michel; Auger, Michèle; Liu, Xiang-Qin; Rainey, Jan K

    2015-01-01

    Spiders store spidroins in their silk glands as high concentration aqueous solutions, spinning these dopes into fibres with outstanding mechanical properties. Aciniform (or wrapping) silk is the toughest spider silk and is devoid of the short amino acid sequence motifs characteristic of the other spidroins. Using solution-state NMR spectroscopy, we demonstrate that the 200 amino acid Argiope trifasciata AcSp1 repeat unit contrasts with previously characterized spidroins, adopting a globular 5-helix bundle flanked by intrinsically disordered N- and C-terminal tails. Split-intein-mediated segmental NMR-active isotope-enrichment allowed unambiguous demonstration of modular and malleable "beads-on-a-string" concatemeric behaviour. Concatemers form fibres upon manual drawing with silk-like morphology and mechanical properties, alongside secondary structuring and orientation consistent with native AcSp1 fibres. AcSp1 structural stability varies locally, with the fifth helix denaturing most readily. The structural transition of aciniform spidroin from a mostly α-helical dope to a mixed α-helix/β-sheet-containing fibre can be directly related to spidroin architecture and stability. PMID:26112753

  9. Spider wrapping silk fibre architecture arising from its modular soluble protein precursor

    PubMed Central

    Tremblay, Marie-Laurence; Xu, Lingling; Lefèvre, Thierry; Sarker, Muzaddid; Orrell, Kathleen E.; Leclerc, Jérémie; Meng, Qing; Pézolet, Michel; Auger, Michèle; Liu, Xiang-Qin; Rainey, Jan K.

    2015-01-01

    Spiders store spidroins in their silk glands as high concentration aqueous solutions, spinning these dopes into fibres with outstanding mechanical properties. Aciniform (or wrapping) silk is the toughest spider silk and is devoid of the short amino acid sequence motifs characteristic of the other spidroins. Using solution-state NMR spectroscopy, we demonstrate that the 200 amino acid Argiope trifasciata AcSp1 repeat unit contrasts with previously characterized spidroins, adopting a globular 5-helix bundle flanked by intrinsically disordered N- and C-terminal tails. Split-intein-mediated segmental NMR-active isotope-enrichment allowed unambiguous demonstration of modular and malleable “beads-on-a-string” concatemeric behaviour. Concatemers form fibres upon manual drawing with silk-like morphology and mechanical properties, alongside secondary structuring and orientation consistent with native AcSp1 fibres. AcSp1 structural stability varies locally, with the fifth helix denaturing most readily. The structural transition of aciniform spidroin from a mostly α-helical dope to a mixed α-helix/β-sheet-containing fibre can be directly related to spidroin architecture and stability. PMID:26112753

  10. Spider wrapping silk fibre architecture arising from its modular soluble protein precursor

    NASA Astrophysics Data System (ADS)

    Tremblay, Marie-Laurence; Xu, Lingling; Lefèvre, Thierry; Sarker, Muzaddid; Orrell, Kathleen E.; Leclerc, Jérémie; Meng, Qing; Pézolet, Michel; Auger, Michèle; Liu, Xiang-Qin; Rainey, Jan K.

    2015-06-01

    Spiders store spidroins in their silk glands as high concentration aqueous solutions, spinning these dopes into fibres with outstanding mechanical properties. Aciniform (or wrapping) silk is the toughest spider silk and is devoid of the short amino acid sequence motifs characteristic of the other spidroins. Using solution-state NMR spectroscopy, we demonstrate that the 200 amino acid Argiope trifasciata AcSp1 repeat unit contrasts with previously characterized spidroins, adopting a globular 5-helix bundle flanked by intrinsically disordered N- and C-terminal tails. Split-intein-mediated segmental NMR-active isotope-enrichment allowed unambiguous demonstration of modular and malleable “beads-on-a-string” concatemeric behaviour. Concatemers form fibres upon manual drawing with silk-like morphology and mechanical properties, alongside secondary structuring and orientation consistent with native AcSp1 fibres. AcSp1 structural stability varies locally, with the fifth helix denaturing most readily. The structural transition of aciniform spidroin from a mostly α-helical dope to a mixed α-helix/β-sheet-containing fibre can be directly related to spidroin architecture and stability.

  11. Constructing modular and universal single molecule tension sensor using protein G to study mechano-sensitive receptors

    PubMed Central

    Wang, Xuefeng; Rahil, Zainab; Li, Isaac T. S.; Chowdhury, Farhan; Leckband, Deborah E.; Chemla, Yann R.; Ha, Taekjip

    2016-01-01

    Recently a variety of molecular force sensors have been developed to study cellular forces acting through single mechano-sensitive receptors. A common strategy adopted is to attach ligand molecules on a surface through engineered molecular tethers which report cell-exerted tension on receptor-ligand bonds. This approach generally requires chemical conjugation of the ligand to the force reporting tether which can be time-consuming and labor-intensive. Moreover, ligand-tether conjugation can severely reduce the activity of protein ligands. To address this problem, we developed a Protein G (ProG)-based force sensor in which force-reporting tethers are conjugated to ProG instead of ligands. A recombinant ligand fused with IgG-Fc is conveniently assembled with the force sensor through ProG:Fc binding, therefore avoiding ligand conjugation and purification processes. Using this approach, we determined that molecular tension on E-cadherin is lower than dsDNA unzipping force (nominal value: 12 pN) during initial cadherin-mediated cell adhesion, followed by an escalation to forces higher than 43 pN (nominal value). This approach is highly modular and potentially universal as we demonstrate using two additional receptor-ligand interactions, P-selectin & PSGL-1 and Notch & DLL1. PMID:26875524

  12. Analysis of the Linker Region Joining the Adenylation and Carrier Protein Domains of the Modular Non-Ribosomal Peptide Synthetases

    PubMed Central

    Miller, Bradley R.; Sundlov, Jesse A.; Drake, Eric J.; Makin, Thomas A.; Gulick, Andrew M.

    2014-01-01

    Non-Ribosomal Peptide Synthetases (NRPSs) are multi-modular proteins capable of producing important peptide natural products. Using an assembly-line process the amino acid substrate and peptide intermediates are passed between the active sites of different catalytic domains of the NRPS while bound covalently to a peptidyl carrier protein (PCP) domain. Examination of the linker sequences that join the NRPS adenylation and PCP domains identified several conserved proline residues that are not found in standalone adenylation domains. We examined the roles of these proline residues and neighboring conserved sequences through mutagenesis and biochemical analysis of the reaction catalyzed by the adenylation domain and the fully reconstituted NRPS pathway. In particular, we identified a conserved LPxP motif at the start of the adenylation-PCP linker. The LPxP motif interacts with a region on the adenylation domain to stabilize a critical catalytic lysine residue belonging to the A10 motif that immediately precedes the linker. Further, this interaction with the C-terminal sub-domain of the adenylation domain may coordinate movement of the PCP with the conformational change of the adenylation domain. Through this work, we extend the conserved A10 motif of the adenylation domain and identify residues that enable proper adenylation domain function. PMID:24975514

  13. Helical repeats modular proteins are major players for organelle gene expression.

    PubMed

    Hammani, Kamel; Bonnard, Géraldine; Bouchoucha, Ayoub; Gobert, Anthony; Pinker, Franziska; Salinas, Thalia; Giegé, Philippe

    2014-05-01

    Mitochondria and chloroplasts are often described as semi-autonomous organelles because they have retained a genome. They thus require fully functional gene expression machineries. Many of the required processes going all the way from transcription to translation have specificities in organelles and arose during eukaryote history. Most factors involved in these RNA maturation steps have remained elusive for a long time. The recent identification of a number of novel protein families including pentatricopeptide repeat proteins, half-a-tetratricopeptide proteins, octotricopeptide repeat proteins and mitochondrial transcription termination factors has helped to settle long-standing questions regarding organelle gene expression. In particular, their functions have been related to replication, transcription, RNA processing, RNA editing, splicing, the control of RNA turnover and translation throughout eukaryotes. These families of proteins, although evolutionary independent, seem to share a common overall architecture. For all of them, proteins contain tandem arrays of repeated motifs. Each module is composed of two to three α-helices and their succession forms a super-helix. Here, we review the features characterising these protein families, in particular, their distribution, the identified functions and mode of action and propose that they might share similar substrate recognition mechanisms. PMID:24021622

  14. Modularity of Protein Folds as a Tool for Template-Free Modeling of Structures

    PubMed Central

    Vallat, Brinda; Madrid-Aliste, Carlos; Fiser, Andras

    2015-01-01

    Predicting the three-dimensional structure of proteins from their amino acid sequences remains a challenging problem in molecular biology. While the current structural coverage of proteins is almost exclusively provided by template-based techniques, the modeling of the rest of the protein sequences increasingly require template-free methods. However, template-free modeling methods are much less reliable and are usually applicable for smaller proteins, leaving much space for improvement. We present here a novel computational method that uses a library of supersecondary structure fragments, known as Smotifs, to model protein structures. The library of Smotifs has saturated over time, providing a theoretical foundation for efficient modeling. The method relies on weak sequence signals from remotely related protein structures to create a library of Smotif fragments specific to the target protein sequence. This Smotif library is exploited in a fragment assembly protocol to sample decoys, which are assessed by a composite scoring function. Since the Smotif fragments are larger in size compared to the ones used in other fragment-based methods, the proposed modeling algorithm, SmotifTF, can employ an exhaustive sampling during decoy assembly. SmotifTF successfully predicts the overall fold of the target proteins in about 50% of the test cases and performs competitively when compared to other state of the art prediction methods, especially when sequence signal to remote homologs is diminishing. Smotif-based modeling is complementary to current prediction methods and provides a promising direction in addressing the structure prediction problem, especially when targeting larger proteins for modeling. PMID:26252221

  15. Multifunctional imaging nanoprobes

    PubMed Central

    Jarzyna, Peter A.; Gianella, Anita; Skajaa, Torjus; Knudsen, Gitte; Deddens, Lisette H.; Cormode, David P.; Fayad, Zahi A.; Mulder, Willem J. M.

    2011-01-01

    Multifunctional imaging nanoprobes have proven to be of great value in the research of pathological processes, as well as the assessment of the delivery, fate, and therapeutic potential of encapsulated drugs. Moreover, such probes may potentially support therapy schemes by the exploitation of their own physical properties, e.g., through thermal ablation. This review will present four classes of nanoparticulate imaging probes used in this area: multifunctional probes (1) that can be tracked with at least three different and complementary imaging techniques, (2) that carry a drug and have bimodal imaging properties, (3) that are employed for nucleic acid delivery and imaging, and (4) imaging probes with capabilities that can be used for thermal ablation. We will highlight several examples where the suitable combination of different (bio)materials like polymers, inorganic nanocrystals, fluorophores, proteins/peptides, and lipids can be tailored to manufacture multifunctional probes to accomplish nanomaterials of each of the aforementioned classes. Moreover, it will be demonstrated how multimodality imaging approaches improve our understanding of in vivo nanoparticle behavior and efficacy at different levels, ranging from the subcellular level to the whole body. PMID:20039335

  16. A Modular Approach To Study Protein Adsorption on Surface Modified Hydroxyapatite.

    PubMed

    Ozhukil Kollath, Vinayaraj; Van den Broeck, Freya; Fehér, Krisztina; Martins, José C; Luyten, Jan; Traina, Karl; Mullens, Steven; Cloots, Rudi

    2015-07-13

    Biocompatible inorganic nano- and microcarriers can be suitable candidates for protein delivery. This study demonstrates facile methods of functionalization by using nanoscale linker molecules to change the protein adsorption capacity of hydroxyapatite (HA) powder. The adsorption capacity of bovine serum albumin as a model protein has been studied with respect to the surface modifications. The selected linker molecules (lysine, arginine, and phosphoserine) can influence the adsorption capacity by changing the electrostatic nature of the HA surface. Qualitative and quantitative analyses of linker-molecule interactions with the HA surface have been performed by using NMR spectroscopy, zeta-potential measurements, X-ray photoelectron spectroscopy, and thermogravimetric analyses. Additionally, correlations to theoretical isotherm models have been calculated with respect to Langmuir and Freundlich isotherms. Lysine and arginine increased the protein adsorption, whereas phosphoserine reduced the protein adsorption. The results show that the adsorption capacity can be controlled with different functionalization, depending on the protein-carrier selections under consideration. The scientific knowledge acquired from this study can be applied in various biotechnological applications that involve biomolecule-inorganic material interfaces. PMID:26096378

  17. Dissecting the Critical Factors for Thermodynamic Stability of Modular Proteins Using Molecular Modeling Approach

    PubMed Central

    Lee, Sang-Chul; Han, Jieun; Heu, Woosung; Park, Keunwan; Kim, Hyun Jung; Cheong, Hae-Kap; Kim, Dongsup; Kim, Hak-Sung; Lee, Keun Woo

    2014-01-01

    Repeat proteins have recently attracted much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural and biophysical features. In particular, repeat proteins show high stability against temperature and chaotic agents. Despite many studies, structural features for the stability of repeat proteins remain poorly understood. Here we present an interesting result from in silico analyses pursuing the factors which affect the stability of repeat proteins. Previously developed repebody structure based on variable lymphocytes receptors (VLRs) which consists of leucine-rich repeat (LRR) modules was used as initial structure for the present study. We constructed extra six repebody structures with varying numbers of repeat modules and those structures were used for molecular dynamics simulations. For the structures, the intramolecular interactions including backbone H-bonds, van der Waals energy, and hydrophobicity were investigated and then the radius of gyration, solvent-accessible surface area, ratio of secondary structure, and hydration free energy were also calculated to find out the relationship between the number of LRR modules and stability of the protein. Our results show that the intramolecular interactions lead to more compact structure and smaller surface area of the repebodies, which are critical for the stability of repeat proteins. The other features were also well compatible with the experimental results. Based on our observations, the repebody-5 was proposed as the best structure from the all repebodies in structure optimization process. The present study successfully demonstrated that our computer-based molecular modeling approach can significantly contribute to the experiment-based protein engineering challenge. PMID:24849801

  18. The multifunctional role of the pallilysin-associated Treponema pallidum protein, Tp0750, in promoting fibrinolysis and extracellular matrix component degradation.

    PubMed

    Houston, Simon; Russell, Shannon; Hof, Rebecca; Roberts, Alanna K; Cullen, Paul; Irvine, Kyle; Smith, Derek S; Borchers, Christoph H; Tonkin, Michelle L; Boulanger, Martin J; Cameron, Caroline E

    2014-02-01

    The mechanisms that facilitate dissemination of the highly invasive spirochaete, Treponema pallidum, are incompletely understood. Previous studies showed the treponemal metalloprotease pallilysin (Tp0751) possesses fibrin clot degradation capability, suggesting a role in treponemal dissemination. In the current study we report characterization of the functionally linked protein Tp0750. Structural modelling predicts Tp0750 contains a von Willebrand factor type A (vWFA) domain, a protein-protein interaction domain commonly observed in extracellular matrix (ECM)-binding proteins. We report Tp0750 is a serine protease that degrades the major clot components fibrinogen and fibronectin. We also demonstrate Tp0750 cleaves a matrix metalloprotease (MMP) peptide substrate that is targeted by several MMPs, enzymes central to ECM remodelling. Through proteomic analyses we show Tp0750 binds the endothelial fibrinolytic receptor, annexin A2, in a specific and dose-dependent manner. These results suggest Tp0750 constitutes a multifunctional protein that is able to (1) degrade infection-limiting clots by both inhibiting clot formation through degradation of host coagulation cascade proteins and promoting clot dissolution by complexing with host proteins involved in the fibrinolytic cascade and (2) facilitate ECM degradation via MMP-like proteolysis of host components. We propose that through these activities Tp0750 functions in concert with pallilysin to enable T. pallidum dissemination. PMID:24303899

  19. The Multifunctional Role of the Pallilysin-Associated Treponema pallidum Protein, Tp0750, in Promoting Fibrinolysis and Extracellular Matrix Component Degradation

    PubMed Central

    Houston, Simon; Russell, Shannon; Hof, Rebecca; Roberts, Alanna K.; Cullen, Paul; Irvine, Kyle; Smith, Derek S.; Borchers, Christoph H.; Tonkin, Michelle L.; Boulanger, Martin J.; Cameron, Caroline E.

    2014-01-01

    Summary The mechanisms that facilitate dissemination of the highly invasive spirochete, Treponema pallidum, are incompletely understood. Previous studies showed the treponemal metalloprotease pallilysin (Tp0751) possesses fibrin clot degradation capability, suggesting a role in treponemal dissemination. In the current study we report characterization of the functionally-linked protein Tp0750. Structural modelling predicts Tp0750 contains a von Willebrand factor type A (vWFA) domain, a protein-protein interaction domain commonly observed in extracellular matrix (ECM)-binding proteins. We report Tp0750 is a serine protease that degrades the major clot components fibrinogen and fibronectin. We also demonstrate Tp0750 cleaves a matrix metalloprotease (MMP) peptide substrate that is targeted by several MMPs, enzymes central to ECM remodelling. Through proteomic analyses we show Tp0750 binds the endothelial fibrinolytic receptor, annexin A2, in a specific and dose-dependent manner. These results suggest Tp0750 constitutes a multifunctional protein that is able to (1) degrade infection-limiting clots by both inhibiting clot formation through degradation of host coagulation cascade proteins and promoting clot dissolution by complexing with host proteins involved in the fibrinolytic cascade and (2) facilitate ECM degradation via MMP-like proteolysis of host components. We propose that through these activities Tp0750 functions in concert with pallilysin to enable T. pallidum dissemination. PMID:24303899

  20. ELM server: a new resource for investigating short functional sites in modular eukaryotic proteins

    PubMed Central

    Puntervoll, Pål; Linding, Rune; Gemünd, Christine; Chabanis-Davidson, Sophie; Mattingsdal, Morten; Cameron, Scott; Martin, David M. A.; Ausiello, Gabriele; Brannetti, Barbara; Costantini, Anna; Ferrè, Fabrizio; Maselli, Vincenza; Via, Allegra; Cesareni, Gianni; Diella, Francesca; Superti-Furga, Giulio; Wyrwicz, Lucjan; Ramu, Chenna; McGuigan, Caroline; Gudavalli, Rambabu; Letunic, Ivica; Bork, Peer; Rychlewski, Leszek; Küster, Bernhard; Helmer-Citterich, Manuela; Hunter, William N.; Aasland, Rein; Gibson, Toby J.

    2003-01-01

    Multidomain proteins predominate in eukaryotic proteomes. Individual functions assigned to different sequence segments combine to create a complex function for the whole protein. While on-line resources are available for revealing globular domains in sequences, there has hitherto been no comprehensive collection of small functional sites/motifs comparable to the globular domain resources, yet these are as important for the function of multidomain proteins. Short linear peptide motifs are used for cell compartment targeting, protein–protein interaction, regulation by phosphorylation, acetylation, glycosylation and a host of other post-translational modifications. ELM, the Eukaryotic Linear Motif server at http://elm.eu.org/, is a new bioinformatics resource for investigating candidate short non-globular functional motifs in eukaryotic proteins, aiming to fill the void in bioinformatics tools. Sequence comparisons with short motifs are difficult to evaluate because the usual significance assessments are inappropriate. Therefore the server is implemented with several logical filters to eliminate false positives. Current filters are for cell compartment, globular domain clash and taxonomic range. In favourable cases, the filters can reduce the number of retained matches by an order of magnitude or more. PMID:12824381

  1. Molecular Architecture and Evolution of a Modular Spider Silk Protein Gene

    NASA Astrophysics Data System (ADS)

    Hayashi, Cheryl Y.; Lewis, Randolph V.

    2000-02-01

    Spider flagelliform silk is one of the most elastic natural materials known. Extensive sequencing of spider silk genes has shown that the exons and introns of the flagelliform gene underwent intragenic concerted evolution. The intron sequences are more homogenized within a species than are the exons. This pattern can be explained by extreme mutation and recombination pressures on the internally repetitive exons. The iterated sequences within exons encode protein structures that are critical to the function of silks. Therefore, attributes that make silks exceptional biomaterials may also hinder the fixation of optimally adapted protein sequences.

  2. Secondary Structural Change Can Occur Diffusely and Not Modularly during Protein Folding and Unfolding Reactions.

    PubMed

    Malhotra, Pooja; Udgaonkar, Jayant B

    2016-05-11

    A major goal of protein folding studies is to understand the structural basis of the coupling between stabilizing interactions, which leads to cooperative conformational change. The goal is challenging because of the difficulty in simultaneously measuring global cooperativity by determining population distributions of the conformations present, and the structures of these conformations. Here, hydrogen exchange (HX) into the small protein monellin was carried out under conditions where structure-opening is rate limiting for most backbone amide sites. Detection by mass spectrometry allowed characterization of not only segment-specific structure-opening rates but also the cooperativity of unfolding of the different secondary structural segments of the protein. The segment-specific pattern of HX reveals that the backbone hydrogen-bonding network disassembles in a structurally diffuse, asynchronous manner. A comparison of the site-specific transient opening rates of secondary and tertiary structure in the protein provides a structural rationale for the observation that unfolding is hierarchical and describable by exponential kinetics, despite being diffuse. Since unfolding was studied in native conditions, the sequence of events during folding in the same conditions will be the reverse of the sequence of events observed during unfolding. Hence, the formation of secondary structural units during folding would also occur in a non-cooperative, diffuse, and asynchronous manner. PMID:27093885

  3. The elastic free energy of a tandem modular protein under force.

    PubMed

    Valle-Orero, Jessica; Eckels, Edward C; Stirnemann, Guillaume; Popa, Ionel; Berkovich, Ronen; Fernandez, Julio M

    2015-05-01

    Recent studies have provided a theoretical framework for including entropic elasticity in the free energy landscape of proteins under mechanical force. Accounting for entropic elasticity using polymer physics models has helped explain the hopping behavior seen in single molecule experiments in the low force regime. Here, we expand on the construction of the free energy of a single protein domain under force proposed by Berkovich et al. to provide a free energy landscape for N tandem domains along a continuous polypeptide. Calculation of the free energy of individual domains followed by their concatenation provides a continuous free energy landscape whose curvature is dominated by the worm-like chain at forces below 20 pN. We have validated our free energy model using Brownian dynamics and reproduce key features of protein folding. This free energy model can predict the effects of changes in the elastic properties of a multidomain protein as a consequence of biological modifications such as phosphorylation or the formation of disulfide bonds. This work lays the foundations for the modeling of tissue elasticity, which is largely determined by the properties of tandem polyproteins. PMID:25796331

  4. Modular Total Synthesis of Protein Kinase C Activator (-)-Indolactam V.

    PubMed

    Haynes-Smith, Jeremy; Diaz, Italia; Billingsley, Kelvin L

    2016-05-01

    A concise, eight-step total synthesis of (-)-indolactam V, a nanomolar agonist of protein kinase C, is reported. The synthesis relies upon an efficient copper-catalyzed amino acid arylation to establish the indole C4-nitrogen bond. This cross-coupling method is applicable to a range of hydrophobic amino acids, providing a platform for further diversification of indolactam alkaloid scaffolds and studies on their potent biological activity. PMID:27074538

  5. Modularity of Escherichia coli sRNA regulation revealed by sRNA-target and protein network analysis

    PubMed Central

    2010-01-01

    Background sRNAs, which belong to the non-coding RNA family and range from approximately 50 to 400 nucleotides, serve various important gene regulatory roles. Most are believed to be trans-regulating and function by being complementary to their target mRNAs in order to inhibiting translation by ribosome occlusion. Despite this understanding of their functionality, the global properties associated with regulation by sRNAs are not yet understood. Here we use topological analysis of sRNA targets in terms of protein-protein interaction and transcription-regulatory networks in Escherichia coli to shed light on the global correlation between sRNA regulation and cellular control networks. Results The analysis of sRNA targets in terms of their networks showed that some specific network properties could be identified. In protein-protein interaction network, sRNA targets tend to occupy more central positions (higher closeness centrality, p-val = 0.022) and more cliquish (larger clustering coefficient, p-val = 0.037). The targets of the same sRNA tend to form a network module (shorter characteristic path length, p-val = 0.015; larger density, p-val = 0.019; higher in-degree ratio, p-val = 0.009). Using the transcription-regulatory network, sRNA targets tend to be under multiple regulation (higher indegree, p-val = 0.013) and the targets usually are important to the transfer of regulatory signals (higher betweenness, p-val = 0.012). As was found for the protein-protein interaction network, the targets that are regulated by the same sRNA also tend to be closely knit within the transcription-regulatory network (larger density, p-val = 0.036), and inward interactions between them are greater than the outward interactions (higher in-degree ratio, p-val = 0.023). However, after incorporating information on predicted sRNAs and down-stream targets, the results are not as clear-cut, but the overall network modularity is still evident. Conclusions Our results indicate that s

  6. A modular perspective of protein structures; application to fragment based loop modeling

    PubMed Central

    Fernandez-Fuentes, Narcis; Fiser, Andras

    2013-01-01

    Summary Proteins can be decomposed into supersecondary structure modules. We used a generic definition of supersecondary structure elements, so-called Smotifs, which are composed of two flanking regular secondary structures connected by a loop, to explore the evolution and current variety of structure building blocks. Here, we discuss recent observations about the saturation of Smotif geometries in protein structures and how it opens new avenues in protein structure modeling and design. As a first application of these observations we describe our loop conformation modeling algorithm, ArchPred that takes advantage of Smotifs classification. In this application, instead of focusing on specific loop properties the method narrows down possible template conformations in other, often not homologous structures, by identifying the most likely supersecondary structure environment that cradles the loop. Beyond identifying the correct starting supersecondary structure geometry, it takes into account information of fit of anchor residues, sterical clashes, match of predicted and observed dihedral angle preferences, and local sequence signal. PMID:22987351

  7. Modular entanglement.

    PubMed

    Gualdi, Giulia; Giampaolo, Salvatore M; Illuminati, Fabrizio

    2011-02-01

    We introduce and discuss the concept of modular entanglement. This is the entanglement that is established between the end points of modular systems composed by sets of interacting moduli of arbitrarily fixed size. We show that end-to-end modular entanglement scales in the thermodynamic limit and rapidly saturates with the number of constituent moduli. We clarify the mechanisms underlying the onset of entanglement between distant and noninteracting quantum systems and its optimization for applications to quantum repeaters and entanglement distribution and sharing. PMID:21405382

  8. Modular evolution of glutathione peroxidase genes in association with different biochemical properties of their encoded proteins in invertebrate animals

    PubMed Central

    Bae, Young-An; Cai, Guo-Bin; Kim, Seon-Hee; Zo, Young-Gun; Kong, Yoon

    2009-01-01

    Background Phospholipid hydroperoxide glutathione peroxidases (PHGPx), the most abundant isoforms of GPx families, interfere directly with hydroperoxidation of lipids. Biochemical properties of these proteins vary along with their donor organisms, which has complicated the phylogenetic classification of diverse PHGPx-like proteins. Despite efforts for comprehensive analyses, the evolutionary aspects of GPx genes in invertebrates remain largely unknown. Results We isolated GPx homologs via in silico screening of genomic and/or expressed sequence tag databases of eukaryotic organisms including protostomian species. Genes showing strong similarity to the mammalian PHGPx genes were commonly found in all genomes examined. GPx3- and GPx7-like genes were additionally detected from nematodes and platyhelminths, respectively. The overall distribution of the PHGPx-like proteins with different biochemical properties was biased across taxa; selenium- and glutathione (GSH)-dependent proteins were exclusively detected in platyhelminth and deuterostomian species, whereas selenium-independent and thioredoxin (Trx)-dependent enzymes were isolated in the other taxa. In comparison of genomic organization, the GSH-dependent PHGPx genes showed a conserved architectural pattern, while their Trx-dependent counterparts displayed complex exon-intron structures. A codon for the resolving Cys engaged in reductant binding was found to be substituted in a series of genes. Selection pressure to maintain the selenocysteine codon in GSH-dependent genes also appeared to be relaxed during their evolution. With the dichotomized fashion in genomic organizations, a highly polytomic topology of their phylogenetic trees implied that the GPx genes have multiple evolutionary intermediate forms. Conclusion Comparative analysis of invertebrate GPx genes provides informative evidence to support the modular pathways of GPx evolution, which have been accompanied with sporadic expansion/deletion and exon

  9. Plasmodium Cysteine Repeat Modular Proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host

    PubMed Central

    2011-01-01

    Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δpcrmp3 and Δpcrmp4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δpcrmp3 and Δpcrmp4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2. Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δcrmp3 and Δcrmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life cycle; they are essential

  10. Multifunctional interpenetrating polymer network hydrogels based on methacrylated alginate for the delivery of small molecule drugs and sustained release of protein.

    PubMed

    Zhao, Jun; Zhao, Xin; Guo, Baolin; Ma, Peter X

    2014-09-01

    Multifunctional injectable thermo-/pH-responsive hydrogels as release systems for the oral delivery of small molecule drugs and the local delivery of protein are presented. The injectable interpenetrating polymer network (IPN) hydrogels based on poly(ethylene glycol) methacrylate, N-isopropylacrylamide, and methacrylated alginate were prepared by using ammonium persulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED) as a redox initiator system at body temperature, and the obtained hydrogels overcame the instability of calcium cross-linked alginate hydrogels under physiological conditions. The hydrogels showed good mechanical strength by rheometer and exhibited temperature and pH sensitivity by a swelling test. Diclofenac sodium (DCS) as a model for small molecule water-soluble anti-inflammatory drugs and bovine serum albumin (BSA) as a model for protein drugs were encapsulated in situ in the hydrogel. The DCS and BSA release results indicated that these hydrogels, as carriers, have great potential for use in the oral delivery of small molecule drugs and for long-term localized protein release. Furthermore, the cytotoxicity of these hydrogels was studied via live/dead viability and alamarBlue assays using adipose tissue-derived mesenchymal stem cells. PMID:25102223

  11. The structure of the folded domain from the signature multifunctional protein ICP27 from herpes simplex virus-1 reveals an intertwined dimer

    PubMed Central

    Tunnicliffe, Richard B.; Schacht, Mitchell; Levy, Colin; Jowitt, Thomas A.; Sandri-Goldin, Rozanne M.; Golovanov, Alexander P.

    2015-01-01

    Herpesviruses cause life-long infections by evading the host immune system and establishing latent infections. All mammalian herpesviruses express an essential multifunctional protein that is typified by ICP27 encoded by Herpes Simplex Virus 1. The only region that is conserved among the diverse members of the ICP27 family is a predicted globular domain that has been termed the ICP27 homology domain. Here we present the first crystal structure of the ICP27 homology domain, solved to 1.9 Å resolution. The protein is a homo-dimer, adopting a novel intertwined fold with one CHCC zinc-binding site per monomer. The dimerization, which was independently confirmed by SEC-MALS and AUC, is stabilized by an extensive network of intermolecular contacts, and a domain-swap involving the two N-terminal helices and C-terminal tails. Each monomer contains a lid motif that can clamp the C-terminal tail of its dimeric binding partner against its globular core, without forming any distinct secondary structure elements. The binding interface was probed with point mutations, none of which had a noticeable effect on dimer formation; however deletion of the C-terminal tail region prevented dimer formation in vivo. The structure provides a template for future biochemical studies and modelling of ICP27 homologs from other herpesviruses. PMID:26062451

  12. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 suppresses tumor growth in breast cancer-bearing mice by negatively regulating myeloid-derived suppressor cell functions.

    PubMed

    Hong, Hye-Jin; Lim, Hui Xuan; Song, Ju Han; Lee, Arim; Kim, Eugene; Cho, Daeho; Cohen, Edward P; Kim, Tae Sung

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) are one of the most important cell types that contribute to negative regulation of immune responses in the tumor microenvironment. Recently, aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1), a novel pleiotropic cytokine, was identified as an antitumor protein that inhibits angiogenesis and induces antitumor responses. However, the effect of AIMP1 on MDSCs in the tumor environment remains unclear. In the present study, we demonstrated that AIMP1 significantly inhibited tumor growth in 4T1 breast cancer-bearing mice and reduced MDSCs population of tumor sites and spleens of tumor-bearing mice. AIMP1 reduced expansion of MDSCs from bone marrow-derived cells in the tumor-conditioned media. AIMP1 also negatively regulated suppressive activities of MDSCs by inhibiting IL-6 and NO production, and Arg-1 expression. Furthermore, treatment of breast cancer-bearing mice with AIMP1 decreased the capacity of MDSCs to suppress T cell proliferation and Treg cell induction. Western blot and inhibition experiments showed that downregulation of MDSCs functions by AIMP1 may result from attenuated activation of STATs, Akt, and ERK. These findings indicate that AIMP1 plays an essential role in negative regulation of suppressive functions of MDSCs. Therefore, it has a significant potential as a therapeutic agent for cancer treatment. PMID:26613952

  13. Thick-walled carbon composite multifunctional structures

    NASA Astrophysics Data System (ADS)

    Haake, John M.; Jacobs, Jack H.; McIlroy, Bruce E.

    1997-06-01

    Satellite programs are moving in the direction of smaller and lighter structures. Technological advances have permitted more sophisticated equipment to be consolidated into compact spaces. Micro-satellites, between 10 and 100 kg, will incorporate micro-electric devices into the lay-up of the satellite structure. These structures will be designed to carry load, provide thermal control, enhance damping, and include integrated passive electronics. These multifunctional structures offer lighter weight, reduced volume, and a 'smarter' overall package for incorporation of sensors, electronics, fiber optics, powered appendages or active components. McDonnell Douglas Corporation (MDC) has applied technology from the synthesis and processing of intelligent cost effective structures (SPICES) and independent research and development (IRAD) programs to the modular instrument support system (MISS) for multifunctional space structures and micro-satellites. The SPICES program was funded by the Defense Advanced Research Projects Agency (DARPA) to develop affordable manufacturing processes for smart materials to be used in vibration control, and the MISS program was funded by NASA-Langley. The MISS program was conceived to develop concepts and techniques to make connections between different multifunctional structures. MDA fabricated a trapezoidal carbon composite structure out of IM7/977-3 tape prepreg. Flex circuits, thermal and optical conduits were embedded to realize a utility modular connector. These provide electrical, thermal, optical and mechanical connections between micro- satellite components. A quick disconnect mount was also developed to accommodate a variety of devices such as solar arrays, power sources, thermal transfer and vibration control modules.

  14. Theory for the Emergence of Modularity in Complex Systems

    NASA Astrophysics Data System (ADS)

    Deem, Michael; Park, Jeong-Man

    2013-03-01

    Biological systems are modular, and this modularity evolves over time and in different environments. A number of observations have been made of increased modularity in biological systems under increased environmental pressure. We here develop a theory for the dynamics of modularity in these systems. We find a principle of least action for the evolved modularity at long times. In addition, we find a fluctuation dissipation relation for the rate of change of modularity at short times. We discuss a number of biological and social systems that can be understood with this framework. The modularity of the protein-protein interaction network increases when yeast are exposed to heat shock, and the modularity of the protein-protein networks in both yeast and E. coli appears to have increased over evolutionary time. Food webs in low-energy, stressful environments are more modular than those in plentiful environments, arid ecologies are more modular during droughts, and foraging of sea otters is more modular when food is limiting. The modularity of social networks changes over time: stock brokers instant messaging networks are more modular under stressful market conditions, criminal networks are more modular under increased police pressure, and world trade network modularity has decreased

  15. Design and characterization of a modular membrane protein anchor to functionalize the moss Physcomitrella patens with extracellular catalytic and/or binding activities.

    PubMed

    Morath, Volker; Truong, Dong-Jiunn Jeffery; Albrecht, Florian; Polte, Ingmar; Ciccone, Rosario Adriano; Funke, Louise Friederike; Reichart, Leonie; Wolf, Christopher Guy; Brunner, Andreas-David; Fischer, Katrin; Schneider, Philipp Constantin; Brüggenthies, Johanna Barbara; Fröhlich, Fabian; Wiedemann, Gertrud; Reski, Ralf; Skerra, Arne

    2014-12-19

    Heterologous enzymes and binding proteins were secreted by the moss Physcomitrella patens or anchored extracellularly on its cell membrane in order to functionalize the apoplast as a biochemical reaction compartment. This modular membrane anchoring system utilizes the signal peptide and the transmembrane segment of the somatic embryogenesis receptor-like kinase (SERK), which were identified in a comprehensive bioinformatic analysis of the P. patens genome. By fusing the soluble enzyme NanoLuc luciferase to the signal peptide, its secretion capability was confirmed in vivo. The membrane localization of hybrid proteins comprising the SERK signal peptide, NanoLuc or other functional modules, the SERK transmembrane anchor, and a C-terminal GFP reporter was demonstrated using fluorescence microscopy as well as site-specific proteolytic release of the extracellular enzyme domain. Our membrane anchoring system enables the expression of various functional proteins in the apoplast of P. patens, empowering this photoautotrophic organism for biotechnological applications. PMID:25524107

  16. Multifunctional roles for the N-terminal basic motif of Alfalfa mosaic virus coat protein: nucleolar/cytoplasmic shuttling, modulation of RNA-binding activity, and virion formation.

    PubMed

    Herranz, Mari Carmen; Pallas, Vicente; Aparicio, Frederic

    2012-08-01

    In addition to virion formation, the coat protein (CP) of Alfalfa mosaic virus (AMV) is involved in the regulation of replication and translation of viral RNAs, and in cell-to-cell and systemic movement of the virus. An intriguing feature of the AMV CP is its nuclear and nucleolar accumulation. Here, we identify an N-terminal lysine-rich nucleolar localization signal (NoLS) in the AMV CP required to both enter the nucleus and accumulate in the nucleolus of infected cells, and a C-terminal leucine-rich domain which might function as a nuclear export signal. Moreover, we demonstrate that AMV CP interacts with importin-α, a component of the classical nuclear import pathway. A mutant AMV RNA 3 unable to target the nucleolus exhibited reduced plus-strand RNA synthesis and cell-to-cell spread. Moreover, virion formation and systemic movement were completely abolished in plants infected with this mutant. In vitro analysis demonstrated that specific lysine residues within the NoLS are also involved in modulating CP-RNA binding and CP dimerization, suggesting that the NoLS represents a multifunctional domain within the AMV CP. The observation that nuclear and nucleolar import signals mask RNA-binding properties of AMV CP, essential for viral replication and translation, supports a model in which viral expression is carefully modulated by a cytoplasmic/nuclear balance of CP accumulation. PMID:22746826

  17. Protein-Assisted Assembly of Modular 3D Plasmonic Raspberry-like Core/Satellite Nanoclusters: Correlation of Structure and Optical Properties

    PubMed Central

    Höller, Roland P. M.; Dulle, Martin; Thomä, Sabrina; Mayer, Martin; Steiner, Anja Maria; Förster, Stephan; Fery, Andreas

    2016-01-01

    We present a bottom-up assembly route for a large-scale organization of plasmonic nanoparticles (NPs) into three-dimensional (3D) modular assemblies with core/satellite structure. The protein-assisted assembly of small spherical gold or silver NPs with a hydrophilic protein shell (as satellites) onto larger metal NPs (as cores) offers high modularity in sizes and composition at high satellite coverage (close to the jamming limit). The resulting dispersions of metal/metal nanoclusters exhibit high colloidal stability and therefore allow for high concentrations and a precise characterization of the nanocluster architecture in dispersion by small-angle X-ray scattering (SAXS). Strong near-field coupling between the building blocks results in distinct regimes of dominant satellite-to-satellite and core-to-satellite coupling. High robustness against satellite disorder was proved by UV/vis diffuse reflectance (integrating sphere) measurements. Generalized multiparticle Mie theory (GMMT) simulations were employed to describe the electromagnetic coupling within the nanoclusters. The close correlation of structure and optical property allows for the rational design of core/satellite nanoclusters with tailored plasmonics and well-defined near-field enhancement, with perspectives for applications such as surface-enhanced spectroscopies. PMID:26982386

  18. Protein-Assisted Assembly of Modular 3D Plasmonic Raspberry-like Core/Satellite Nanoclusters: Correlation of Structure and Optical Properties.

    PubMed

    Höller, Roland P M; Dulle, Martin; Thomä, Sabrina; Mayer, Martin; Steiner, Anja Maria; Förster, Stephan; Fery, Andreas; Kuttner, Christian; Chanana, Munish

    2016-06-28

    We present a bottom-up assembly route for a large-scale organization of plasmonic nanoparticles (NPs) into three-dimensional (3D) modular assemblies with core/satellite structure. The protein-assisted assembly of small spherical gold or silver NPs with a hydrophilic protein shell (as satellites) onto larger metal NPs (as cores) offers high modularity in sizes and composition at high satellite coverage (close to the jamming limit). The resulting dispersions of metal/metal nanoclusters exhibit high colloidal stability and therefore allow for high concentrations and a precise characterization of the nanocluster architecture in dispersion by small-angle X-ray scattering (SAXS). Strong near-field coupling between the building blocks results in distinct regimes of dominant satellite-to-satellite and core-to-satellite coupling. High robustness against satellite disorder was proved by UV/vis diffuse reflectance (integrating sphere) measurements. Generalized multiparticle Mie theory (GMMT) simulations were employed to describe the electromagnetic coupling within the nanoclusters. The close correlation of structure and optical property allows for the rational design of core/satellite nanoclusters with tailored plasmonics and well-defined near-field enhancement, with perspectives for applications such as surface-enhanced spectroscopies. PMID:26982386

  19. Quasispecies Theory for Evolution of Modularity

    PubMed Central

    Park, Jeong-Man; Niestemski, Liang Ren; Deem, Michael W.

    2015-01-01

    Biological systems are modular, and this modularity evolves over time and in different environments. A number of observations have been made of increased modularity in biological systems under increased environmental pressure. We here develop a quasispecies theory for the dynamics of modularity in populations of these systems. We show how the steady-state fitness in a randomly changing environment can be computed. We derive a fluctuation dissipation relation for the rate of change of modularity and use it to derive a relationship between rate of environmental changes and rate of growth of modularity. We also find a principle of least action for the evolved modularity at steady state. Finally, we compare our predictions to simulations of protein evolution and find them to be consistent. PMID:25679649

  20. Integration of binding peptide selection and multifunctional particles as tool-box for capture of soluble proteins in serum.

    PubMed

    Cusano, Angela Maria; Causa, Filippo; Moglie, Raffaella Della; Falco, Nunzia; Scognamiglio, Pasqualina Liana; Aliberti, Anna; Vecchione, Raffaele; Battista, Edmondo; Marasco, Daniela; Savarese, Marika; Raucci, Umberto; Rega, Nadia; Netti, Paolo Antonio

    2014-10-01

    In this paper, we report on a general approach for the detection of a specific tumoural biomarker directly in serum. Such detection is made possible using a protein-binding peptide selected through an improved phage display technique and then conjugated to engineered microparticles (MPs). Protein biomarkers represent an unlimited source of information for non-invasive diagnostic and prognostic tests; MP-based assays are becoming largely used in manipulation of soluble biomarkers, but their direct use in serum is hampered by the complex biomolecular environment. Our technique overcomes the current limitations as it produces a selective MP--engineered with an antifouling layer--that 'captures' the relevant protein staying impervious to the background. Our system succeeds in fishing-out the human tumour necrosis factor alpha directly in serum with a high selectivity degree. Our method could have great impact in soluble protein manipulation and detection for a wide variety of diagnostic applications. PMID:25100324

  1. Integration of binding peptide selection and multifunctional particles as tool-box for capture of soluble proteins in serum

    PubMed Central

    Cusano, Angela Maria; Causa, Filippo; Moglie, Raffaella Della; Falco, Nunzia; Scognamiglio, Pasqualina Liana; Aliberti, Anna; Vecchione, Raffaele; Battista, Edmondo; Marasco, Daniela; Savarese, Marika; Raucci, Umberto; Rega, Nadia; Netti, Paolo Antonio

    2014-01-01

    In this paper, we report on a general approach for the detection of a specific tumoural biomarker directly in serum. Such detection is made possible using a protein-binding peptide selected through an improved phage display technique and then conjugated to engineered microparticles (MPs). Protein biomarkers represent an unlimited source of information for non-invasive diagnostic and prognostic tests; MP-based assays are becoming largely used in manipulation of soluble biomarkers, but their direct use in serum is hampered by the complex biomolecular environment. Our technique overcomes the current limitations as it produces a selective MP—engineered with an antifouling layer—that ‘captures’ the relevant protein staying impervious to the background. Our system succeeds in fishing-out the human tumour necrosis factor alpha directly in serum with a high selectivity degree. Our method could have great impact in soluble protein manipulation and detection for a wide variety of diagnostic applications. PMID:25100324

  2. Two modular forms of the mitochondrial sorting and assembly machinery are involved in biogenesis of alpha-helical outer membrane proteins.

    PubMed

    Thornton, Nicolas; Stroud, David A; Milenkovic, Dusanka; Guiard, Bernard; Pfanner, Nikolaus; Becker, Thomas

    2010-02-26

    The mitochondrial outer membrane contains two translocase machineries for precursor proteins--the translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex). The TOM complex functions as the main mitochondrial entry gate for nuclear-encoded proteins, whereas the SAM complex was identified according to its function in the biogenesis of beta-barrel proteins of the outer membrane. The SAM complex is required for the assembly of precursors of the TOM complex, including not only the beta-barrel protein Tom40 but also a subset of alpha-helical subunits. While the interaction of beta-barrel proteins with the SAM complex has been studied in detail, little is known about the interaction between the SAM complex and alpha-helical precursor proteins. We report that the SAM is not static but that the SAM core complex can associate with different partner proteins to form two large SAM complexes with different functions in the biogenesis of alpha-helical Tom proteins. We found that a subcomplex of TOM, Tom5-Tom40, associates with the SAM core complex to form a new large SAM complex. This SAM-Tom5/Tom40 complex binds the alpha-helical precursor of Tom6 after the precursor has been inserted into the outer membrane in an Mim1 (mitochondrial import protein 1)-dependent manner. The second large SAM complex, SAM-Mdm10 (mitochondrial distribution and morphology protein), binds the alpha-helical precursor of Tom22 and promotes its membrane integration. We suggest that the modular composition of the SAM complex provides a flexible platform to integrate the sorting pathways of different precursor proteins and to promote their assembly into oligomeric complexes. PMID:20026336

  3. Evolution of Efficient Modular Polyketide Synthases by Homologous Recombination.

    PubMed

    Chemler, Joseph A; Tripathi, Ashootosh; Hansen, Douglas A; O'Neil-Johnson, Mark; Williams, Russell B; Starks, Courtney; Park, Sung Ryeol; Sherman, David H

    2015-08-26

    The structural scaffolds of many complex natural products are produced by multifunctional type I polyketide synthase (PKS) enzymes that operate as biosynthetic assembly lines. The modular nature of these mega-enzymes presents an opportunity to construct custom biocatalysts built in a lego-like fashion by inserting, deleting, or exchanging native or foreign domains to produce targeted variants of natural polyketides. However, previously engineered PKS enzymes are often impaired resulting in limited production compared to native systems. Here, we show a versatile method for generating and identifying functional chimeric PKS enzymes for synthesizing custom macrolactones and macrolides. PKS genes from the pikromycin and erythromycin pathways were hybridized in Saccharomyces cerevisiae to generate hybrid libraries. We used a 96-well plate format for plasmid purification, transformations, sequencing, protein expression, in vitro reactions and analysis of metabolite formation. Active chimeric enzymes were identified with new functionality. Streptomyces venezuelae strains that expressed these PKS chimeras were capable of producing engineered macrolactones. Furthermore, a macrolactone generated from selected PKS chimeras was fully functionalized into a novel macrolide analogue. This method permits the engineering of PKS pathways as modular building blocks for the production of new antibiotic-like molecules. PMID:26230368

  4. Modular shield

    DOEpatents

    Snyder, Keith W.

    2002-01-01

    A modular system for containing projectiles has a sheet of material including at least a polycarbonate layer held by a metal frame having a straight frame member corresponding to each straight edge of the sheet. Each frame member has a U-shaped shield channel covering and holding a straight edge of the sheet and an adjacent U-shaped clamp channel rigidly held against the shield channel. A flexible gasket separates each sheet edge from its respective shield channel; and each frame member is fastened to each adjacent frame member only by clamps extending between adjacent clamp channels.

  5. The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans.

    PubMed

    Choy, Henry A; Kelley, Melissa M; Croda, Julio; Matsunaga, James; Babbitt, Jane T; Ko, Albert I; Picardeau, Mathieu; Haake, David A

    2011-01-01

    Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9-11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react

  6. Local modularity for community detection in complex networks

    NASA Astrophysics Data System (ADS)

    Xiang, Ju; Hu, Tao; Zhang, Yan; Hu, Ke; Li, Jian-Ming; Xu, Xiao-Ke; Liu, Cui-Cui; Chen, Shi

    2016-02-01

    Community detection is a topic of interest in the study of complex networks such as the protein-protein interaction networks and metabolic networks. In recent years, various methods were proposed to detect community structures of the networks. Here, a kind of local modularity with tunable parameter is derived from the Newman-Girvan modularity by a special self-loop strategy that depends on the community division of the networks. By the self-loop strategy, one can easily control the definition of modularity, and the resulting modularity can be optimized by using the existing modularity optimization algorithms. The local modularity is used as the target function for community detection, and a self-consistent method is proposed for the optimization of the local modularity. We analyze the behaviors of the local modularity and show the validity of the local modularity in detecting community structures on various networks.

  7. ATP-binding sites in brain p97/VCP (valosin-containing protein), a multifunctional AAA ATPase.

    PubMed Central

    Zalk, Ran; Shoshan-Barmatz, Varda

    2003-01-01

    VCP (valosin-containing protein) or p97 is a member of the AAA family (ATPases associated with a variety of cellular activities family), a diverse group of proteins sharing a key conserved AAA module containing duplicate putative ATP-binding sites. Although the functions of the AAA family are related to their putative ATP-binding sites, the binding of ATP to these sites has not yet been demonstrated. In the present study, the ATP-binding site(s) of brain VCP was characterized using the photoreactive ATP analogue, BzATP [3'- O -(4-benzoylbenzoyl)ATP]. Photo-activation of Bz-[alpha-(32)P]ATP resulted in its covalent binding to a 97-kDa purified soluble or membrane-associated protein, identified by amino acid sequencing as VCP. Bz-[alpha-(32)P]ATP covalently bound to the purified homo-hexameric VCP with an apparent high affinity (74-111 nM). A molar stoichiometry of 2.23+/-0.14 BzATP bound per homo-hexameric VCP (n =6) was determined using different methods for analysis of radiolabelling and protein determination. Nucleotides inhibited the binding of Bz-[alpha-(32)P]ATP to VCP with the following efficiency: BzATP>ATP>ADP>>adenosine 5'-[beta,gamma-imido]triphosphate>or=adenosine 5'-[beta,gamma-methylene]triphosphate, whereas AMP, GTP and CTP were ineffective. VCP was observed to possess very low ATPase activity, with nucleotide specificity similar to that for BzATP binding. Conformational changes induced by an alternating site mechanism for ATP binding are suggested as a molecular mechanism for coupling ATP binding to the diverse activities of the AAA family. PMID:12747802

  8. Three different proteins recognize a multifunctional determinant that controls replication initiation, fork arrest and transcription in Tetrahymena.

    PubMed

    Mohammad, M; Saha, S; Kapler, G M

    2000-02-01

    Type I elements regulate the initiation of DNA replication, elongation of replication forks and transcription of the Tetrahymena thermophila rDNA minichromosome. Previous studies identified a 24 kDa protein, ssA-TIBF, which binds the A-rich strand of type I elements. Here we describe two additional type I element binding activities (native mol. wt approximately 65 and approximately 250 kDa) that interact with DNA via previously unidentified 32 and 110 kDa polypeptides. The 65 kDa activity was purified to homogeneity and consists of a homodimer of a 32 kDa polypeptide. In contrast to the other type I element binding factors, the 65 kDa activity partitions preferentially to the nuclear fraction during isolation. Levels of the 65 kDa activity increase dramatically in starved cells, raising the possibility that it might negatively regulate replication or transcription. By comparison, the other two binding activities were elevated slightly during macronuclear development, when the rDNA was undergoing DNA replication. Previous studies indicate that the initiation of rDNA replication is regulated by long range interactions between dispersed type I elements. Competitive DNA binding or cooperative protein-protein interactions between the factors described here may play a regulatory role in replication or expression of the rDNA minichromosome. PMID:10637338

  9. Modular Certification

    NASA Technical Reports Server (NTRS)

    Rushby, John; Miner, Paul S. (Technical Monitor)

    2002-01-01

    Airplanes are certified as a whole: there is no established basis for separately certifying some components, particularly software-intensive ones, independently of their specific application in a given airplane. The absence of separate certification inhibits the development of modular components that could be largely "precertified" and used in several different contexts within a single airplane, or across many different airplanes. In this report, we examine the issues in modular certification of software components and propose an approach based on assume-guarantee reasoning. We extend the method from verification to certification by considering behavior in the presence of failures. This exposes the need for partitioning, and separation of assumptions and guarantees into normal and abnormal cases. We then identify three classes of property that must be verified within this framework: safe function, true guarantees, and controlled failure. We identify a particular assume-guarantee proof rule (due to McMillan) that is appropriate to the applications considered, and formally verify its soundness in PVS.

  10. Quantitative Fragmentome Mapping Reveals Novel, Domain-specific Partners for the Modular Protein RepoMan (Recruits PP1 Onto Mitotic Chromatin at Anaphase)*

    PubMed Central

    Prévost, Michèle; Chamousset, Delphine; Nasa, Isha; Freele, Emily; Morrice, Nick; Moorhead, Greg; Trinkle-Mulcahy, Laura

    2013-01-01

    RepoMan is a protein phosphatase 1 (PP1) regulatory subunit that targets the phosphatase to key substrates throughout the cell cycle. Most work to date has focused on the mitotic roles of RepoMan/PP1, although equally important interphase role(s) have been demonstrated. Initial mapping of the interactome of nuclear RepoMan, both endogenous and tagged, was complicated by various factors, including antibody cross-reactivity and low sensitivity of the detection of chromatin-associated partners above the high background of proteins that bind nonspecifically to affinity matrices. We therefore adapted the powerful combination of fluorescence imaging with labeling-based quantitative proteomics to map the “fragmentomes” of specific regions of RepoMan. These regions demonstrate distinct localization patterns and turnover dynamics that reflect underlying binding events. The increased sensitivity and signal-to-noise ratio provided by this unique approach facilitated identification of a large number of novel RepoMan interactors, several of which were rigorously validated in follow-up experiments, including the association of RepoMan/PP1 with a specific PP2A-B56γ complex, interaction with ribosomal proteins and import factors involved in their nucleocytoplasmic transport and interaction with proteins involved in the response to DNA damage. This same strategy can be used to investigate the cellular roles of other modular proteins. PMID:23362328

  11. Coevolution, modularity and human disease.

    PubMed

    Fraser, Hunter B

    2006-12-01

    The concepts of coevolution and modularity have been studied separately for decades. Recent advances in genomics have led to the first systematic studies in each of these fields at the molecular level, resulting in several important discoveries. Both coevolution and modularity appear to be pervasive features of genomic data from all species studied to date, and their presence can be detected in many types of datasets, including genome sequences, gene expression data, and protein-protein interaction data. Moreover, the combination of these two ideas might have implications for our understanding of many aspects of biology, ranging from the general architecture of living systems to the causes of various human diseases. PMID:17005391

  12. The complex subcellular distribution of satellite panicum mosaic virus capsid protein reflects its multifunctional role during infection

    SciTech Connect

    Qi Dong; Omarov, Rustem T.; Scholthof, Karen-Beth G.

    2008-06-20

    Satellite panicum mosaic virus (SPMV) depends on its helper Panicum mosaic virus for replication and movement in host plants. The positive-sense single-stranded genomic RNA of SPMV encodes a 17-kDa capsid protein (CP) to form 16-nm virions. We determined that SPMV CP accumulates in both cytosolic and non-cytosolic fractions, but cytosolic accumulation of SPMV CP is exclusively associated with virions. An N-terminal arginine-rich motif (N-ARM) on SPMV CP is used to bind its cognate RNA and to form virus particles. Intriguingly, virion formation is dispensable for successful systemic SPMV RNA accumulation, yet this process still depends on an intact N-ARM. In addition, a C-terminal domain on the SPMV CP is necessary for self-interaction. Biochemical fractionation and fluorescent microscopy of green fluorescent protein-tagged SPMV CP demonstrated that the non-cytosolic SPMV CP is associated with the cell wall, the nucleus and other membranous organelles. To our knowledge, this is the first report that a satellite virus CP not only accumulates exclusively as virions in the cytosol but also is directed to the nucleolus and membranes. That SPMV CP is found both in the nucleus and the cell wall suggests its involvement in viral nuclear import and cell-to-cell transport.

  13. Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer

    PubMed Central

    Vanharanta, Sakari; Marney, Christina B; Shu, Weiping; Valiente, Manuel; Zou, Yilong; Mele, Aldo; Darnell, Robert B; Massagué, Joan

    2014-01-01

    The mechanisms through which cancer cells lock in altered transcriptional programs in support of metastasis remain largely unknown. Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we identified RNA binding motif protein 47 (RBM47) as a suppressor of breast cancer progression and metastasis. RBM47 inhibited breast cancer re-initiation and growth in experimental models. Transcriptome-wide HITS-CLIP analysis revealed widespread RBM47 binding to mRNAs, most prominently in introns and 3′UTRs. RBM47 altered splicing and abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1, inhibit tumor progression downstream of RBM47. Our work identifies RBM47 as an RNA-binding protein that can suppress breast cancer progression and demonstrates how the inactivation of a broadly targeted RNA chaperone enables selection of a pro-metastatic state. DOI: http://dx.doi.org/10.7554/eLife.02734.001 PMID:24898756

  14. The emergence of modularity in biological systems

    NASA Astrophysics Data System (ADS)

    Lorenz, Dirk M.; Jeng, Alice; Deem, Michael W.

    2011-06-01

    In this review, we discuss modularity and hierarchy in biological systems. We review examples from protein structure, genetics, and biological networks of modular partitioning of the geometry of biological space. We review theories to explain modular organization of biology, with a focus on explaining how biology may spontaneously organize to a structured form. That is, we seek to explain how biology nucleated from among the many possibilities in chemistry. The emergence of modular organization of biological structure will be described as a symmetry-breaking phase transition, with modularity as the order parameter. Experimental support for this description will be reviewed. Examples will be presented from pathogen structure, metabolic networks, gene networks, and protein-protein interaction networks. Additional examples will be presented from ecological food networks, developmental pathways, physiology, and social networks.

  15. gC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection.

    PubMed

    Ghebrehiwet, B; Lim, B L; Kumar, R; Feng, X; Peerschke, E I

    2001-04-01

    as a ligand indicate that both cC1q-R and gC1q-R are co-immunoprecipitated with anti-C1q. Taken together, the evidence accumulated to date supports the concept that in addition to its intracellular localization, gC1q-R is expressed on the cell surface and can serve as a binding site for plasma and microbial proteins, but also challenges the existing paradigm that mitochondrial proteins never leave their designated compartment. It is therefore proposed that gC1q-R belongs to a growing list of a class of proteins initially targeted to the mitochondria but then exported to different compartments of the cell through specific mechanisms which have yet to be identified. The designation 'multifunctional and multicompartmental cellular proteins' is proposed for this class of proteins. PMID:11414365

  16. Multifunctional layered magnetic composites.

    PubMed

    Siglreitmeier, Maria; Wu, Baohu; Kollmann, Tina; Neubauer, Martin; Nagy, Gergely; Schwahn, Dietmar; Pipich, Vitaliy; Faivre, Damien; Zahn, Dirk; Fery, Andreas; Cölfen, Helmut

    2015-01-01

    A fabrication method of a multifunctional hybrid material is achieved by using the insoluble organic nacre matrix of the Haliotis laevigata shell infiltrated with gelatin as a confined reaction environment. Inside this organic scaffold magnetite nanoparticles (MNPs) are synthesized. The amount of MNPs can be controlled through the synthesis protocol therefore mineral loadings starting from 15 wt % up to 65 wt % can be realized. The demineralized organic nacre matrix is characterized by small-angle and very-small-angle neutron scattering (SANS and VSANS) showing an unchanged organic matrix structure after demineralization compared to the original mineralized nacre reference. Light microscopy and confocal laser scanning microscopy studies of stained samples show the presence of insoluble proteins at the chitin surface but not between the chitin layers. Successful and homogeneous gelatin infiltration in between the chitin layers can be shown. The hybrid material is characterized by TEM and shows a layered structure filled with MNPs with a size of around 10 nm. Magnetic analysis of the material demonstrates superparamagnetic behavior as characteristic for the particle size. Simulation studies show the potential of collagen and chitin to act as nucleators, where there is a slight preference of chitin over collagen as a nucleator for magnetite. Colloidal-probe AFM measurements demonstrate that introduction of a ferrogel into the chitin matrix leads to a certain increase in the stiffness of the composite material. PMID:25671158

  17. Multifunctional layered magnetic composites

    PubMed Central

    Siglreitmeier, Maria; Wu, Baohu; Kollmann, Tina; Neubauer, Martin; Nagy, Gergely; Schwahn, Dietmar; Pipich, Vitaliy; Faivre, Damien; Zahn, Dirk; Fery, Andreas

    2015-01-01

    Summary A fabrication method of a multifunctional hybrid material is achieved by using the insoluble organic nacre matrix of the Haliotis laevigata shell infiltrated with gelatin as a confined reaction environment. Inside this organic scaffold magnetite nanoparticles (MNPs) are synthesized. The amount of MNPs can be controlled through the synthesis protocol therefore mineral loadings starting from 15 wt % up to 65 wt % can be realized. The demineralized organic nacre matrix is characterized by small-angle and very-small-angle neutron scattering (SANS and VSANS) showing an unchanged organic matrix structure after demineralization compared to the original mineralized nacre reference. Light microscopy and confocal laser scanning microscopy studies of stained samples show the presence of insoluble proteins at the chitin surface but not between the chitin layers. Successful and homogeneous gelatin infiltration in between the chitin layers can be shown. The hybrid material is characterized by TEM and shows a layered structure filled with MNPs with a size of around 10 nm. Magnetic analysis of the material demonstrates superparamagnetic behavior as characteristic for the particle size. Simulation studies show the potential of collagen and chitin to act as nucleators, where there is a slight preference of chitin over collagen as a nucleator for magnetite. Colloidal-probe AFM measurements demonstrate that introduction of a ferrogel into the chitin matrix leads to a certain increase in the stiffness of the composite material. PMID:25671158

  18. Disorder in Milk Proteins: α-Lactalbumin. Part B. A Multifunctional Whey Protein Acting as an Oligomeric Molten Globular "Oil Container" in the Anti-Tumorigenic Drugs, Liprotides.

    PubMed

    Uversky, Vladimir N; Permyakov, Serge E; Breydo, Leonid; Redwan, Elrashdy M; Almehdar, Hussein A; Permyakov, Eugene A

    2016-07-15

    This is a second part of the three-part article from a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. We continue to describe α-lactalbumin, a small globular Ca2+-binding protein, which besides being one of the two components of lactose synthase that catalyzes the final step of the lactose biosynthesis in the lactating mammary gland, possesses a multitude of other functions. In fact, recent studies indicated that some partially folded forms of this protein possess noticeable bactericidal activity and other forms might be related to induction of the apoptosis of tumor cells. In its anti-tumorigenic function, oligomeric α-lactalbumin serves as a founding member of a new family of anticancer drugs termed liprotides (for lipids and partially denatured proteins), where an oligomeric molten globular protein acts as an "oil container" or cargo for the delivery of oleic acid to the cell membranes. PMID:26916155

  19. Multifunctional thin film surface

    SciTech Connect

    Brozik, Susan M.; Harper, Jason C.; Polsky, Ronen; Wheeler, David R.; Arango, Dulce C.; Dirk, Shawn M.

    2015-10-13

    A thin film with multiple binding functionality can be prepared on an electrode surface via consecutive electroreduction of two or more aryl-onium salts with different functional groups. This versatile and simple method for forming multifunctional surfaces provides an effective means for immobilization of diverse molecules at close proximities. The multifunctional thin film has applications in bioelectronics, molecular electronics, clinical diagnostics, and chemical and biological sensing.

  20. Modular robot

    DOEpatents

    Ferrante, T.A.

    1997-11-11

    A modular robot may comprise a main body having a structure defined by a plurality of stackable modules. The stackable modules may comprise a manifold, a valve module, and a control module. The manifold may comprise a top surface and a bottom surface having a plurality of fluid passages contained therein, at least one of the plurality of fluid passages terminating in a valve port located on the bottom surface of the manifold. The valve module is removably connected to the manifold and selectively fluidically connects the plurality of fluid passages contained in the manifold to a supply of pressurized fluid and to a vent. The control module is removably connected to the valve module and actuates the valve module to selectively control a flow of pressurized fluid through different ones of the plurality of fluid passages in the manifold. The manifold, valve module, and control module are mounted together in a sandwich-like manner and comprise a main body. A plurality of leg assemblies are removably connected to the main body and are removably fluidically connected to the fluid passages in the manifold so that each of the leg assemblies can be selectively actuated by the flow of pressurized fluid in different ones of the plurality of fluid passages in the manifold. 12 figs.

  1. Modular robot

    DOEpatents

    Ferrante, Todd A.

    1997-01-01

    A modular robot may comprise a main body having a structure defined by a plurality of stackable modules. The stackable modules may comprise a manifold, a valve module, and a control module. The manifold may comprise a top surface and a bottom surface having a plurality of fluid passages contained therein, at least one of the plurality of fluid passages terminating in a valve port located on the bottom surface of the manifold. The valve module is removably connected to the manifold and selectively fluidically connects the plurality of fluid passages contained in the manifold to a supply of pressurized fluid and to a vent. The control module is removably connected to the valve module and actuates the valve module to selectively control a flow of pressurized fluid through different ones of the plurality of fluid passages in the manifold. The manifold, valve module, and control module are mounted together in a sandwich-like manner and comprise a main body. A plurality of leg assemblies are removably connected to the main body and are removably fluidically connected to the fluid passages in the manifold so that each of the leg assemblies can be selectively actuated by the flow of pressurized fluid in different ones of the plurality of fluid passages in the manifold.

  2. Terpene Biosynthesis: Modularity Rules

    PubMed Central

    Oldfield, Eric; Lin, Fu-Yang

    2013-01-01

    Terpenes are the largest class of small molecule natural products on Earth, and the most abundant by mass. Here, we summarize recent developments in elucidating the structure and function of the proteins involved in their biosynthesis. There are 6 main building blocks or modules (α,β,γ,δ,ε and ζ) that make up the structures of these enzymes: the αα and αδ head-to-tail trans-prenyl transferases that produce trans-isoprenoid diphosphates from C5 precursors; the ε head-to-head prenyl transferases that convert these diphosphates into the tri-and tetra-terpene precursors of sterols, hopanoids and carotenoids; the βγ di- and tri-terpene synthases; the ζ head-to-tail cis-prenyl transferases that produce the cis-isoprenoid diphosphates involved in bacterial cell wall biosynthesis, and finally the α, αβ and αβγ terpene synthases that produce plant terpenes, with many of these modular enzymes having originated from ancestral α and β domain proteins. We also review progress in determining the structure and function of the two 4Fe-4S reductases involved in formation of the C5 diphosphates in many bacteria, where again, highly modular structures are found. PMID:22105807

  3. Lightweight composites for modular panelized construction

    NASA Astrophysics Data System (ADS)

    Vaidya, Amol S.

    Rapid advances in construction materials technology have enabled civil engineers to achieve impressive gains in the safety, economy, and functionality of structures built to serve the common needs of society. Modular building systems is a fast-growing modern, form of construction gaining recognition for its increased efficiency and ability to apply modern technology to the needs of the market place. In the modular construction technique, a single structural panel can perform a number of functions such as providing thermal insulation, vibration damping, and structural strength. These multifunctional panels can be prefabricated in a manufacturing facility and then transferred to the construction site. A system that uses prefabricated panels for construction is called a "panelized construction system". This study focuses on the development of pre-cast, lightweight, multifunctional sandwich composite panels to be used for panelized construction. Two thermoplastic composite panels are proposed in this study, namely Composite Structural Insulated Panels (CSIPs) for exterior walls, floors and roofs, and Open Core Sandwich composite for multifunctional interior walls of a structure. Special manufacturing techniques are developed for manufacturing these panels. The structural behavior of these panels is analyzed based on various building design codes. Detailed descriptions of the design, cost analysis, manufacturing, finite element modeling and structural testing of these proposed panels are included in this study in the of form five peer-reviewed journal articles. The structural testing of the proposed panels involved in this study included flexural testing, axial compression testing, and low and high velocity impact testing. Based on the current study, the proposed CSIP wall and floor panels were found satisfactory, based on building design codes ASCE-7-05 and ACI-318-05. Joining techniques are proposed in this study for connecting the precast panels on the construction

  4. All in the family: structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly.

    PubMed Central

    Bergdoll, M.; Eltis, L. D.; Cameron, A. D.; Dumas, P.; Bolin, J. T.

    1998-01-01

    The crystal structures of three proteins of diverse function and low sequence similarity were analyzed to evaluate structural and evolutionary relationships. The proteins include a bacterial bleomycin resistance protein, a bacterial extradiol dioxygenase, and human glyoxalase I. Structural comparisons, as well as phylogenetic analyses, strongly indicate that the modern family of proteins represented by these structures arose through a rich evolutionary history that includes multiple gene duplication and fusion events. These events appear to be historically shared in some cases, but parallel and historically independent in others. A significant early event is proposed to be the establishment of metal-binding in an oligomeric ancestor prior to the first gene fusion. Variations in the spatial arrangements of homologous modules are observed that are consistent with the structural principles of three-dimensional domain swapping, but in the unusual context of the formation of larger monomers from smaller dimers or tetramers. The comparisons support a general mechanism for metalloprotein evolution that exploits the symmetry of a homooligomeric protein to originate a metal binding site and relies upon the relaxation of symmetry, as enabled by gene duplication, to establish and refine specific functions. PMID:10082363

  5. A RepA-like protein from bacteriophage BFK20 is a multifunctional protein with primase, polymerase, NTPase and helicase activities.

    PubMed

    Halgasova, Nora; Solteszova, Barbora; Pevala, Vladimír; Košťan, Július; Kutejová, Eva; Bukovska, Gabriela

    2015-12-01

    Phage BFK20 replication protein gp43 comprises an N-terminal prim-pol domain and a C-terminal domain similar to replicative helicases. We prepared and studied two recombinant proteins: gp43-1 containing both prim-pol and helicase domains, and gp43C with the helicase domain only. A SEC-MALS analysis indicated that gp43-1 forms a hexameric homooligomer. NTPase activity testing revealed that gp43-1 was able to hydrolyze a wide spectrum of NTPs, ATP the most efficiently. The ATPase activity of gp43-1 was strongly dependent on the presence of ssDNA in the reaction, but was low in the presence of dsDNA and in the absence of DNA. On the other hand, the ATPase activity of gp43C was very low regardless of the presence of DNA. The helicase activity of gp43-1 was detected using a fluorescence-based assay with a forked DNA substrate in the presence of ATP. However, no helicase activity could be detected for gp43C. We therefore conclude that the prim-pol domain is essential for the helicase and ssDNA-dependent ATPase activity of gp43-1. PMID:26277776

  6. Portable modular detection system

    DOEpatents

    Brennan, James S.; Singh, Anup; Throckmorton, Daniel J.; Stamps, James F.

    2009-10-13

    Disclosed herein are portable and modular detection devices and systems for detecting electromagnetic radiation, such as fluorescence, from an analyte which comprises at least one optical element removably attached to at least one alignment rail. Also disclosed are modular detection devices and systems having an integrated lock-in amplifier and spatial filter and assay methods using the portable and modular detection devices.

  7. Modern Schools? Think Modular!

    ERIC Educational Resources Information Center

    Jackson, Lisa M.

    1998-01-01

    Examines how modular educational facilities can provide a viable alternative in building construction when speed and safety are key construction issues. Explains the durability of modular structures, their adherence to building codes, and the flexibility that they provide in design and appearance. The advantages to permanent modular construction…

  8. Multifunctional Tanks for Spacecraft

    NASA Technical Reports Server (NTRS)

    Collins, David H.; Lewis, Joseph C.; MacNeal, Paul D.

    2006-01-01

    A document discusses multifunctional tanks as means to integrate additional structural and functional efficiencies into designs of spacecraft. Whereas spacecraft tanks are traditionally designed primarily to store fluids and only secondarily to provide other benefits, multifunctional tanks are designed to simultaneously provide multiple primary benefits. In addition to one or more chamber(s) for storage of fluids, a multifunctional tank could provide any or all of the following: a) Passageways for transferring the fluids; b) Part or all of the primary structure of a spacecraft; c) All or part of an enclosure; d) Mechanical interfaces to components, subsystems, and/or systems; e) Paths and surfaces for transferring heat; f)Shielding against space radiation; j) Shielding against electromagnetic interference; h) Electrically conductive paths and surfaces; and i) Shades and baffles to protect against sunlight and/or other undesired light. Many different multifunctional-tank designs are conceivable. The design of a particular tank can be tailored to the requirements for the spacecraft in which the tank is to be installed. For example, the walls of the tank can be flat or curved or have more complicated shapes, and the tank can include an internal structure for strengthening the tank and/or other uses.

  9. Multifunctional nanoparticles composite for MALDI-MS: Cd2+-doped carbon nanotubes with CdS nanoparticles as the matrix, preconcentrating and accelerating probes of microwave enzymatic digestion of peptides and proteins for direct MALDI-MS analysis.

    PubMed

    Shrivas, Kamlesh; Wu, Hui-Fen

    2010-12-01

    For the first time, we utilized multifunctional nanoparticles composite (NPs composite) for matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) analysis of peptides and proteins. Multiwalled carbon nanotubes doped with Cd(2+) ions and modified with cadmium sulfide NPs were synthesized by a chemical reduction method at room temperature. The multifunctional NPs composite applied for the analysis of peptides and microwave-digested proteins in the atmospheric pressure matrix-assisted laser desorption/ionization ion-trap and MALDI time-of-flight (TOF) mass spectrometry (MS) was successfully demonstrated. The maximum detection sensitivity for peptides in MALDI-MS was achieved by the adsorption of negatively charged peptides onto the surfaces of NP composite through electrostatic interactions. The optimal conditions of peptide mixtures were obtained at 20 min of incubation time using 1 mg of NPs composite when the pH of the sample solution was kept higher than the pI values of peptides. The potentiality of the NP composite in the preconcentration of peptides was compared with that of the individual NP by calculating the preconcentration factors (PF) and found that the NPs composite showed a 4-6 times of PF than the other NPs. In addition, the NPs composite was also applied as heat-absorbing materials for efficient microwave tryptic digestion of cytochrome c and lysozyme from milk protein in MALDI-TOF-MS analysis. We believe that the use of NPs composite technique would be an efficient and powerful preconcentrating tool for MALDI-MS for the study of proteome research. PMID:21053343

  10. Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations.

    PubMed

    Rose, Honor M; Witte, Christopher; Rossella, Federica; Klippel, Stefan; Freund, Christian; Schröder, Leif

    2014-08-12

    Magnetic resonance imaging (MRI) is seriously limited when aiming for visualization of targeted contrast agents. Images are reconstructed from the weak diamagnetic properties of the sample and require an abundant molecule like water as the reporter. Micromolar to millimolar concentrations of conventional contrast agents are needed to generate image contrast, thus excluding many molecular markers as potential targets. To address this limitation, we developed and characterized a functional xenon NMR biosensor that can identify a specific cell surface marker by targeted (129)Xe MRI. Cells expressing the cell surface protein CD14 can be spatially distinguished from control cells with incorporation of as little as 20 nM of the xenon MRI readout unit, cryptophane-A. Cryptophane-A serves as a chemical host for hyperpolarized nuclei and facilitates the sensitivity enhancement achieved by xenon MRI. Although this paper describes the application of a CD14-specific biosensor, the construct has been designed in a versatile, modular fashion. This allows for quick and easy adaptation of the biosensor to any cell surface target for which there is a specific antibody. In addition, the modular design facilitates the creation of a multifunctional probe that incorporates readout modules for different detection methods, such as fluorescence, to complement the primary MRI readout. This modular antibody-based approach not only offers a practical technique with which to screen targets, but one which can be readily applied as the xenon MRI field moves closer to molecular imaging applications in vivo. PMID:25071165

  11. Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations

    PubMed Central

    Rose, Honor M.; Witte, Christopher; Rossella, Federica; Klippel, Stefan; Freund, Christian; Schröder, Leif

    2014-01-01

    Magnetic resonance imaging (MRI) is seriously limited when aiming for visualization of targeted contrast agents. Images are reconstructed from the weak diamagnetic properties of the sample and require an abundant molecule like water as the reporter. Micromolar to millimolar concentrations of conventional contrast agents are needed to generate image contrast, thus excluding many molecular markers as potential targets. To address this limitation, we developed and characterized a functional xenon NMR biosensor that can identify a specific cell surface marker by targeted 129Xe MRI. Cells expressing the cell surface protein CD14 can be spatially distinguished from control cells with incorporation of as little as 20 nM of the xenon MRI readout unit, cryptophane-A. Cryptophane-A serves as a chemical host for hyperpolarized nuclei and facilitates the sensitivity enhancement achieved by xenon MRI. Although this paper describes the application of a CD14-specific biosensor, the construct has been designed in a versatile, modular fashion. This allows for quick and easy adaptation of the biosensor to any cell surface target for which there is a specific antibody. In addition, the modular design facilitates the creation of a multifunctional probe that incorporates readout modules for different detection methods, such as fluorescence, to complement the primary MRI readout. This modular antibody-based approach not only offers a practical technique with which to screen targets, but one which can be readily applied as the xenon MRI field moves closer to molecular imaging applications in vivo. PMID:25071165

  12. Contractive multifunctions, fixed point inclusions and iterated multifunction systems

    NASA Astrophysics Data System (ADS)

    Kunze, H. E.; La Torre, D.; Vrscay, E. R.

    2007-06-01

    We study the properties of multifunction operators that are contractive in the Covitz-Nadler sense. In this situation, such operators T possess fixed points satisfying the relation x[set membership, variant]Tx. We introduce an iterative method involving projections that guarantees convergence from any starting point x0[set membership, variant]X to a point x[set membership, variant]XT, the set of all fixed points of a multifunction operator T. We also prove a continuity result for fixed point sets XT as well as a "generalized collage theorem" for contractive multifunctions. These results can then be used to solve inverse problems involving contractive multifunctions. Two applications of contractive multifunctions are introduced: (i) integral inclusions and (ii) iterated multifunction systems.

  13. Transcriptional activation by the sexual pheromone and wounding: a new gene family from Volvox encoding modular proteins with (hydroxy)proline-rich and metalloproteinase homology domains.

    PubMed

    Hallmann, A; Amon, P; Godl, K; Heitzer, M; Sumper, M

    2001-06-01

    The green alga Volvox represents the simplest kind of multicellular organism: it is composed of only two cell types, somatic and reproductive, making it suitable as a model system. The sexual development of males and females of Volvox carteri is triggered by a sex-inducing pheromone at a concentration of < 10-16 M. Early biochemical responses to the pheromone involve structural modifications within the extracellular matrix (ECM). By differential screenings of cDNA libraries made from mRNAs of pheromone-treated Volvox, four novel genes were identified that encode four closely related Volvox metalloproteinases that we use to define a new protein family, the VMPs. The existence of several features common to matrix glycoproteins, such as signal peptides, a (hydroxy)proline content of 12-25%, and Ser(Pro)2-4 repeats, suggest an extracellular localization of the VMPs within the ECM. Synthesis of VMP cDNAs is triggered not only by the sex-inducing pheromone, but also by wounding, and is restricted to the somatic cell type. Sequence comparisons suggest that the VMPs are members of the MB clan of zinc-dependent matrix metalloproteinases, although the putative zinc binding site of all VMPs is QEXXHXXGXXH rather than HEXXHXXGXXH. The presence of glutamine instead of histidine in the zinc binding motif suggests a novel family, or even clan, of peptidases. Like the matrixin family of human collagenases, Volvox VMPs exhibit a modular structure: they possess a metalloproteinase homology domain and a (hydroxy)proline-rich domain, and one of them, VMP4, also has two additional domains. Metalloproteinases seem to be crucial for biochemical modifications of the ECM during development or after wounding in the lower eukaryote Volvox with only two cell types, just as in higher organisms. PMID:11489172

  14. Multifunctional nanocomposite materials

    SciTech Connect

    Roy, R.; Komarneni, S.

    1991-11-01

    Objective is to examine the low temperature nanocomposite route in the synthesis of multifunctional materials using two-dimensional clays as hosts. After about 8 months, a significant advance was made in the design and synthesis of novel nanocomposite materials, which are nanometal intercalated clays prepared by a low temperature route. A layered V[sub 2]O[sub 5] gel has been made hydrothermally and its cation exchange properties measured. Several pillared clays have also been synthesized and characterized.

  15. Genome-Wide Detection and Analysis of Multifunctional Genes

    PubMed Central

    Pritykin, Yuri; Ghersi, Dario; Singh, Mona

    2015-01-01

    Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms—H. sapiens, D. melanogaster, and S. cerevisiae—and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality. PMID:26436655

  16. Genome-Wide Detection and Analysis of Multifunctional Genes.

    PubMed

    Pritykin, Yuri; Ghersi, Dario; Singh, Mona

    2015-10-01

    Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms--H. sapiens, D. melanogaster, and S. cerevisiae--and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality. PMID:26436655

  17. Modularity of Prosthetic Implants.

    PubMed

    Barrack

    1994-01-01

    The vast majority of total-joint-replacement components currently utilized are modular to some degree. Modularity reduces inventory and increases the surgeon's options in both primary and revision total-joint arthroplasty. Use of a modular interface, however, increases the risk of fretting, wear debris, and dissociation and mismatching of components. The use of modular heads in total hip replacement is firmly established. The occurrence of corrosion and fretting has been recognized, and most manufacturers have improved the quality of the interface to minimize these problems. Modular polyethylene liners also offer advantages, particularly in revision procedures, where the option of additional screw fixation remains important. Many uncemented acetabular components are inserted without screws, which may generate renewed interest in one-piece factory-preassembled components. The conformity, locking mechanism, and nonarticular interface of modular acetabular components have all been studied and improved. Modular tibial components offer additional flexibility in the performance of total knee replacement but introduce the risk of dissociation and increased polyethylene wear; in revision procedures, modularity provides a valuable option for dealing with bone loss and an additional method of fixation by means of press-fit stems. Modular humeral components offer a significant advantage with limited apparent risk; however, longer clinical experience is required to assess potential problems. PMID:10708990

  18. Alternative splice variants in TIM barrel proteins from human genome correlate with the structural and evolutionary modularity of this versatile protein fold.

    PubMed

    Ochoa-Leyva, Adrián; Montero-Morán, Gabriela; Saab-Rincón, Gloria; Brieba, Luis G; Soberón, Xavier

    2013-01-01

    After the surprisingly low number of genes identified in the human genome, alternative splicing emerged as a major mechanism to generate protein diversity in higher eukaryotes. However, it is still not known if its prevalence along the genome evolution has contributed to the overall functional protein diversity or if it simply reflects splicing noise. The (βα)8 barrel or TIM barrel is one of the most frequent, versatile, and ancient fold encountered among enzymes. Here, we analyze the structural modifications present in TIM barrel proteins from the human genome product of alternative splicing events. We found that 87% of all splicing events involved deletions; most of these events resulted in protein fragments that corresponded to the (βα)2, (βα)4, (βα)5, (βα)6, and (βα)7 subdomains of TIM barrels. Because approximately 7% of all the splicing events involved internal β-strand substitutions, we decided, based on the genomic data, to design β-strand and α-helix substitutions in a well-studied TIM barrel enzyme. The biochemical characterization of one of the chimeric variants suggests that some of the splice variants in the human genome with β-strand substitutions may be evolving novel functions via either the oligomeric state or substrate specificity. We provide results of how the splice variants represent subdomains that correlate with the independently folding and evolving structural units previously reported. This work is the first to observe a link between the structural features of the barrel and a recurrent genetic mechanism. Our results suggest that it is reasonable to expect that a sizeable fraction of splice variants found in the human genome represent structurally viable functional proteins. Our data provide additional support for the hypothesis of the origin of the TIM barrel fold through the assembly of smaller subdomains. We suggest a model of how nature explores new proteins through alternative splicing as a mechanism to diversify the

  19. The Rocketdyne Multifunction Tester. Part 1: Test Method

    NASA Technical Reports Server (NTRS)

    Murphy, Brian T.; Scharrer, Joseph K.; Sutton, Robert F.

    1991-01-01

    The Rocketdyne Multifunction Tester is a general purpose test apparatus which utilizes axial and radial magnetic bearings as shaft excitation devices. The tester is modular in design so that different seal and bearing packages can be tested on the same test stand. The tester will be used for rotordynamic coefficient extraction, as well as life and fluid/material compatibility evaluations. Use of a magnetic bearing as a shaft excitation device opens up many possibilities for shaft excitation and rotordynamic coefficient extraction. In addition to describing the basic apparatus, some of the excitation and extraction methods are described. Some of the excitation methods to be discussed include random, aperiodic, harmonic, impulse and chirp.

  20. Modular Buildings Buying Guide.

    ERIC Educational Resources Information Center

    Morris, Susan

    1991-01-01

    Suggests that child care program directors who are expanding their programs or opening new child care centers investigate the possibility of renting, leasing, or purchasing a modular building. Discusses the advantages of modular buildings over conventional building construction or rented space in an occupied building. Provides information about…

  1. Small Modular Biomass Systems

    SciTech Connect

    2002-12-01

    This fact sheet provides information about modular biomass systems. Small modular biomass systems can help supply electricity to rural areas, businesses, and the billions of people who live without power worldwide. These systems use locally available biomass fuels such as wood, crop waste, animal manures, and landfill gas.

  2. Modular avionic architectures

    NASA Astrophysics Data System (ADS)

    Trujillo, Edward

    The author presents an analysis revealing some of the salient features of modular avionics. A decomposition of the modular avionics concept is performed, highlighting some of the key features of such architectures. Several layers of architecture can be found in such concepts, including those relating to software structure, communication, and supportability. Particular emphasis is placed on the layer relating to partitioning, which gives rise to those features of integration, modularity, and commonality. Where integration is the sharing of common tasks or items to gain efficiency and flexibility, modularity is the partitioning of a system into reconfigurable and maintainable items, and commonality is partitioning to maximize the use of identical items across the range of applications. Two architectures, MASA (Modular Avionics System Architecture) and Pave Pillar, are considered in particular.

  3. Templated biomimetic multifunctional coatings

    NASA Astrophysics Data System (ADS)

    Sun, Chih-Hung; Gonzalez, Adriel; Linn, Nicholas C.; Jiang, Peng; Jiang, Bin

    2008-02-01

    We report a bioinspired templating technique for fabricating multifunctional optical coatings that mimic both unique functionalities of antireflective moth eyes and superhydrophobic cicada wings. Subwavelength-structured fluoropolymer nipple arrays are created by a soft-lithography-like process. The utilization of fluoropolymers simultaneously enhances the antireflective performance and the hydrophobicity of the replicated films. The specular reflectivity matches the optical simulation using a thin-film multilayer model. The dependence of the size and the crystalline ordering of the replicated nipples on the resulting antireflective properties have also been investigated by experiment and modeling. These biomimetic materials may find important technological application in self-cleaning antireflection coatings.

  4. Multifunctional reference electrode

    DOEpatents

    Redey, L.; Vissers, D.R.

    1981-12-30

    A multifunctional, low mass reference electrode of a nickel tube, thermocouple means inside the nickel tube electrically insulated therefrom for measuring the temperature thereof, a housing surrounding the nickel tube, an electrolyte having a fixed sulfide ion activity between the housing and the outer surface of the nickel tube forming the nickel/nickel sulfide/sulfide half-cell are described. An ion diffusion barrier is associated with the housing in contact with the electrolyte. Also disclosed is a cell using the reference electrode to measure characteristics of a working electrode.

  5. Multifunctional reference electrode

    DOEpatents

    Redey, Laszlo; Vissers, Donald R.

    1983-01-01

    A multifunctional, low mass reference electrode of a nickel tube, thermocouple means inside the nickel tube electrically insulated therefrom for measuring the temperature thereof, a housing surrounding the nickel tube, an electrolyte having a fixed sulfide ion activity between the housing and the outer surface of the nickel tube forming the nickel/nickel sulfide/sulfide half-cell. An ion diffusion barrier is associated with the housing in contact with the electrolyte. Also disclosed is a cell using the reference electrode to measure characteristics of a working electrode.

  6. Voluntary initiation of movement: multifunctional integration of subjective agency

    PubMed Central

    Grüneberg, Patrick; Kadone, Hideki; Suzuki, Kenji

    2015-01-01

    This paper investigates subjective agency (SA) as a special type of efficacious action consciousness. Our central claims are, firstly, that SA is a conscious act of voluntarily initiating bodily motion. Secondly, we argue that SA is a case of multifunctional integration of behavioral functions being analogous to multisensory integration of sensory modalities. This is based on new perspectives on the initiation of action opened up by recent advancements in robot assisted neuro-rehabilitation which depends on the active participation of the patient and yields experimental evidence that there is SA in terms of a conscious act of voluntarily initiating bodily motion (phenomenal performance). Conventionally, action consciousness has been considered as a sense of agency (SoA). According to this view, the conscious subject merely echoes motor performance and does not cause bodily motion. Depending on sensory input, SoA is implemented by means of unifunctional integration (binding) and inevitably results in non-efficacious action consciousness. In contrast, SA comes as a phenomenal performance which causes motion and builds on multifunctional integration. Therefore, the common conception of the brain should be shifted toward multifunctional integration in order to allow for efficacious action consciousness. For this purpose, we suggest the heterarchic principle of asymmetric reciprocity and neural operators underlying SA. The general idea is that multifunctional integration allows conscious acts to be simultaneously implemented with motor behavior so that the resulting behavior (SA) comes as efficacious action consciousness. Regarding the neural implementation, multifunctional integration rather relies on operators than on modular functions. A robotic case study and possible experimental setups with testable hypotheses building on SA are presented. PMID:26052308

  7. Voluntary initiation of movement: multifunctional integration of subjective agency.

    PubMed

    Grüneberg, Patrick; Kadone, Hideki; Suzuki, Kenji

    2015-01-01

    This paper investigates subjective agency (SA) as a special type of efficacious action consciousness. Our central claims are, firstly, that SA is a conscious act of voluntarily initiating bodily motion. Secondly, we argue that SA is a case of multifunctional integration of behavioral functions being analogous to multisensory integration of sensory modalities. This is based on new perspectives on the initiation of action opened up by recent advancements in robot assisted neuro-rehabilitation which depends on the active participation of the patient and yields experimental evidence that there is SA in terms of a conscious act of voluntarily initiating bodily motion (phenomenal performance). Conventionally, action consciousness has been considered as a sense of agency (SoA). According to this view, the conscious subject merely echoes motor performance and does not cause bodily motion. Depending on sensory input, SoA is implemented by means of unifunctional integration (binding) and inevitably results in non-efficacious action consciousness. In contrast, SA comes as a phenomenal performance which causes motion and builds on multifunctional integration. Therefore, the common conception of the brain should be shifted toward multifunctional integration in order to allow for efficacious action consciousness. For this purpose, we suggest the heterarchic principle of asymmetric reciprocity and neural operators underlying SA. The general idea is that multifunctional integration allows conscious acts to be simultaneously implemented with motor behavior so that the resulting behavior (SA) comes as efficacious action consciousness. Regarding the neural implementation, multifunctional integration rather relies on operators than on modular functions. A robotic case study and possible experimental setups with testable hypotheses building on SA are presented. PMID:26052308

  8. Diversity and Unity of Modularity

    ERIC Educational Resources Information Center

    Seok, Bongrae

    2006-01-01

    Since the publication of Fodor's (1983) The Modularity of Mind, there have been quite a few discussions of cognitive modularity among cognitive scientists. Generally, in those discussions, modularity means a property of specialized cognitive processes or a domain-specific body of information. In actuality, scholars understand modularity in many…

  9. Hierarchical multifunctional nanocomposites

    NASA Astrophysics Data System (ADS)

    Ghasemi-Nejhad, Mehrdad N.

    2014-03-01

    Nanocomposites; including nano-materials such as nano-particles, nanoclays, nanofibers, nanotubes, and nanosheets; are of significant importance in the rapidly developing field of nanotechnology. Due to the nanometer size of these inclusions, their physicochemical characteristics differ significantly from those of micron size and bulk materials. The field of nanocomposites involves the study of multiphase materials where at least one of the constituent phases has one dimension less than 100 nm. This is the range where the phenomena associated with the atomic and molecular interaction strongly influence the macroscopic properties of materials. Since the building blocks of nanocomposites are at nanoscale, they have an enormous surface area with numerous interfaces between the two intermix phases. The special properties of the nano-composite arise from the interaction of its phases at the interface and/or interphase regions. By contrast, in a conventional composite based on micrometer sized filler such as carbon fibers, the interfaces between the filler and matrix constitutes have a much smaller surface-to-volume fraction of the bulk materials, and hence influence the properties of the host structure to a much smaller extent. The optimum amount of nanomaterials in the nanocomposites depends on the filler size, shape, homogeneity of particles distribution, and the interfacial bonding properties between the fillers and matrix. The promise of nanocomposites lies in their multifunctionality, i.e., the possibility of realizing unique combination of properties unachievable with traditional materials. The challenges in reaching this promise are tremendous. They include control over the distribution in size and dispersion of the nanosize constituents, and tailoring and understanding the role of interfaces between structurally or chemically dissimilar phases on bulk properties. While the properties of the matrix can be improved by the inclusions of nanomaterials, the

  10. Modular poly(ethylene glycol) scaffolds provide the ability to decouple the effects of stiffness and protein concentration on PC12 cells.

    PubMed

    Scott, Rebecca A; Elbert, Donald L; Willits, Rebecca Kuntz

    2011-11-01

    This research focused on developing a modular poly(ethylene glycol) (PEG) scaffold, assembled from PEG microgels and collagen I, to provide an environment to decouple the chemical and mechanical cues within a three-dimensional scaffold. We first characterized the microgel fabrication process, examining the size, polydispersity, swelling ratio, mesh size and storage modulus of the polymer particles. The resulting microgels had a low polydispersity index, PDI=1.08, and a diameter of ~1.6 μm. The mesh size of the microgels, calculated from the swelling ratio, was 47.53 Å. Modular hydrogels (modugels) were then formed by compacting N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimidyl group-activated microgels with PEG-4arm-amine and 0, 1, 10, or 100 μg ml(-1) collagen. The stiffness (G(∗)) of the modugels was not significantly altered with the addition of collagen, allowing for modification of the chemical environment independent from the mechanical properties of the scaffold. PC12 cell aggregation increased in modugels as collagen concentrations increased and cell viability in modugels was improved over bulk PEG hydrogels. Overall, these results indicate that further exploration of modular scaffolds formed from microgels could allow for a better understanding of the relationship between the chemical and mechanical properties and cellular behavior. PMID:21787889

  11. Modular tokamak magnetic system

    DOEpatents

    Yang, Tien-Fang

    1988-01-01

    A modular tokamak system comprised of a plurality of interlocking moldules. Each module is comprised of a vacuum vessel section, a toroidal field coil, moldular saddle coils which generate a poloidal magnetic field and ohmic heating coils.

  12. Modularity in signaling systems

    NASA Astrophysics Data System (ADS)

    Del Vecchio, Domitilla

    2012-08-01

    Modularity is a property by which the behavior of a system does not change upon interconnection. It is crucial for understanding the behavior of a complex system from the behavior of the composing subsystems. Whether modularity holds in biology is an intriguing and largely debated question. In this paper, we discuss this question taking a control system theory view and focusing on signaling systems. In particular, we argue that, despite signaling systems being constituted of structural modules, such as covalent modification cycles, modularity does not hold in general. As in any engineering system, impedance-like effects, called retroactivity, appear at interconnections and alter the behavior of connected modules. We further argue that while signaling systems have evolved sophisticated ways to counter-act retroactivity and enforce modularity, retroactivity may also be exploited to finely control the information processing of signaling pathways. Testable predictions and experimental evidence are discussed with their implications.

  13. Multi-functional windows

    NASA Astrophysics Data System (ADS)

    Nag, Nagendra; Goldman, Lee M.; Balasubramanian, Sreeram; Sastri, Suri

    2013-06-01

    The requirements for modern aircraft are driving the need for conformal windows for future sensor systems. However, limitations on optical systems and the physical properties of optically transparent materials currently limit the geometry of existing windows and window assemblies to faceted assemblies of flat windows held in weight bearing frames. Novel material systems will have to be developed which combine different materials (e.g. ductile metals with transparent ceramics) into structures that combine transparency with structural integrity. Surmet's demonstrated ability to produce novel transparent ceramic/metal structures will allow us to produce such structures in the types of conformal shapes required for future aircraft applications. Furthermore, the ability to incorporate transparencies into such structures also holds out the promise of creating multi-functional windows which provide a broad range of capabilities that might include RF antennas and de-icing in addition to transparency. Recent results in this area will be presented.

  14. Comet: Multifunction VOEvent broker

    NASA Astrophysics Data System (ADS)

    Swinbank, John

    2014-04-01

    Comet is a Python implementation of the VOEvent Transport Protocol (VTP). VOEvent is the IVOA system for describing transient celestial events. Details of transients detected by many projects, including Fermi, Swift, and the Catalina Sky Survey, are currently made available as VOEvents, which is also the standard alert format by future facilities such as LSST and SKA. The core of Comet is a multifunction VOEvent broker, capable of receiving events either by subscribing to one or more remote brokers or by direct connection from authors; it can then both process those events locally and forward them to its own subscribers. In addition, Comet provides a tool for publishing VOEvents to the global VOEvent backbone.

  15. Modular avionics packaging standardization

    NASA Astrophysics Data System (ADS)

    Austin, M.; McNichols, J. K.

    The Modular Avionics Packaging (MAP) Program for packaging future military avionics systems with the objective of improving reliability, maintainability, and supportability, and reducing equipment life cycle costs is addressed. The basic MAP packaging concepts called the Standard Avionics Module, the Standard Enclosure, and the Integrated Rack are summarized, and the benefits of modular avionics packaging, including low risk design, technology independence with common functions, improved maintainability and life cycle costs are discussed. Progress made in MAP is briefly reviewed.

  16. Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

    DOEpatents

    Glazer, Alexander N.; Cai, Yuping

    2003-11-18

    The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein, including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

  17. Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

    DOEpatents

    Glazer, Alexander N.; Cai, Yuping

    2007-02-13

    The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein. including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

  18. Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

    DOEpatents

    Glazer, Alexander N.; Cai, Yuping

    2007-01-30

    The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein, including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

  19. Modularity and mental architecture.

    PubMed

    Robbins, Philip

    2013-11-01

    Debates about the modularity of cognitive architecture have been ongoing for at least the past three decades, since the publication of Fodor's landmark book The Modularity of Mind. According to Fodor, modularity is essentially tied to informational encapsulation, and as such is only found in the relatively low-level cognitive systems responsible for perception and language. According to Fodor's critics in the evolutionary psychology camp, modularity simply reflects the fine-grained functional specialization dictated by natural selection, and it characterizes virtually all aspects of cognitive architecture, including high-level systems for judgment, decision making, and reasoning. Though both of these perspectives on modularity have garnered support, the current state of evidence and argument suggests that a broader skepticism about modularity may be warranted. WIREs Cogn Sci 2013, 4:641-649. doi: 10.1002/wcs.1255 CONFLICT OF INTEREST: The author has declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. PMID:26304269

  20. Multifunctional mesoporous silica nanoparticles for combined therapeutic, diagnostic and targeted action in cancer treatment.

    PubMed

    Rosenholm, Jessica M; Sahlgren, Cecilia; Lindén, Mika

    2011-07-01

    The main objective in the development of nanomedicine is to obtain delivery platforms for targeted delivery of drugs or imaging agents for improved therapeutic efficacy, reduced side effects and increased diagnostic sensitivity. A (nano)material class that has been recognized for its controllable properties on many levels is ordered mesoporous inorganic materials, typically in the form of amorphous silica (SiO2). Characteristics for this class of materials include mesoscopic order, tunable pore dimensions in the (macro)molecular size range, a high pore volume and surface area, the possibility for selective surface functionality as well as morphology control. The robust but biodegradable ceramic matrix moreover provides shelter for incorporated agents (drugs, proteins, imaging agents, photosensitizers) leaving the outer particle surface free for further modification. The unique features make these materials particularly amenable to modular design, whereby functional moieties and features may be interchanged or combined to produce multifunctional nanodelivery systems combining targeting, diagnostic, and therapeutic actions. This review covers the latest developments related to the use of mesoporous silica nanoparticles (MSNs) as nanocarriers in biomedical applications, with special focus on cancer therapy and diagnostics. PMID:21443474

  1. Functional group diversity increases with modularity in complex food webs

    PubMed Central

    Montoya, D.; Yallop, M.L.; Memmott, J.

    2015-01-01

    Biodiversity increases the ability of ecosystems to provide multiple functions. Most studies report a positive relationship between species richness and the number of ecosystem functions. However, it is not known whether the number of functional groups is related to the structure of the underlying species interaction network. Here we present food web data from 115 salt marsh islands and show that network structure is associated with the number of functional groups present. Functional group diversity is heterogeneously distributed across spatial scales, with some islands hosting more functional groups than others. Functional groups form modules within the community so that food webs with more modular architectures have more functional group diversity. Further, in communities with different interaction types, modularity can be seen as the multifunctional equivalent of trophic complementarity. Collectively, these findings reveal spatial heterogeneity in the number of functional groups that emerges from patterns in the structure of the food web. PMID:26059871

  2. Self Evolving Modular Network

    NASA Astrophysics Data System (ADS)

    Tokunaga, Kazuhiro; Kawabata, Nobuyuki; Furukawa, Tetsuo

    We propose a novel modular network called the Self-Evolving Modular Network (SEEM). The SEEM has a modular network architecture with a graph structure and these following advantages: (1) new modules are added incrementally to allow the network to adapt in a self-organizing manner, and (2) graph's paths are formed based on the relationships between the models represented by modules. The SEEM is expected to be applicable to evolving functions of an autonomous robot in a self-organizing manner through interaction with the robot's environment and categorizing large-scale information. This paper presents the architecture and an algorithm for the SEEM. Moreover, performance characteristic and effectiveness of the network are shown by simulations using cubic functions and a set of 3D-objects.

  3. Modular optical detector system

    DOEpatents

    Horn, Brent A.; Renzi, Ronald F.

    2006-02-14

    A modular optical detector system. The detector system is designed to detect the presence of molecules or molecular species by inducing fluorescence with exciting radiation and detecting the emitted fluorescence. Because the system is capable of accurately detecting and measuring picomolar concentrations it is ideally suited for use with microchemical analysis systems generally and capillary chromatographic systems in particular. By employing a modular design, the detector system provides both the ability to replace various elements of the detector system without requiring extensive realignment or recalibration of the components as well as minimal user interaction with the system. In addition, the modular concept provides for the use and addition of a wide variety of components, including optical elements (lenses and filters), light sources, and detection means, to fit particular needs.

  4. Symmetric modular torsatron

    DOEpatents

    Rome, J.A.; Harris, J.H.

    1984-01-01

    A fusion reactor device is provided in which the magnetic fields for plasma confinement in a toroidal configuration is produced by a plurality of symmetrical modular coils arranged to form a symmetric modular torsatron referred to as a symmotron. Each of the identical modular coils is helically deformed and comprise one field period of the torsatron. Helical segments of each coil are connected by means of toroidally directed windbacks which may also provide part of the vertical field required for positioning the plasma. The stray fields of the windback segments may be compensated by toroidal coils. A variety of magnetic confinement flux surface configurations may be produced by proper modulation of the winding pitch of the helical segments of the coils, as in a conventional torsatron, winding the helix on a noncircular cross section and varying the poloidal and radial location of the windbacks and the compensating toroidal ring coils.

  5. Induction of innate immune signatures following polyepitope protein-glycoprotein B-TLR4&9 agonist immunization generates multifunctional CMV-specific cellular and humoral immunity

    PubMed Central

    Dasari, Vijayendra; Smith, Corey; Schuessler, Andrea; Zhong, Jie; Khanna, Rajiv

    2014-01-01

    Recent studies have suggested that a successful subunit human cytomegalovirus (CMV) vaccine requires improved formulation to generate broad-based anti-viral immunity following immunization. Here we report the development of a non-live protein-based vaccine strategy for CMV based on a polyepitope protein and CMV glycoprotein B (gB) adjuvanted with TLR4 and/or TLR9 agonists. The polyepitope protein includes contiguous multiple MHC class I-restricted epitopes with an aim to induce CD8+ T cell immunity, while gB is an important target for CD4+ T cell immunity and neutralizing antibodies. Optimal immunogenicity of this bivalent non-live protein vaccine formulation was dependent upon the co-administration of both the TLR4 and TLR9 agonist, which was associated with the activation of innate immune signatures and the influx of different DC subsets including plasmacytoid DCs and migratory CD8-DEC205+CD103-CD326- langerin-negative dermal DCs into the draining lymph nodes. Furthermore these professional antigen presenting cells also expressed IL-6, IL-12p70, TNFα, and IFNα which play a crucial role in the activation of adaptive immunity. In summary, this study provides a novel platform technology in which broad-based anti-CMV immune responses upon vaccination can be maximized by co-delivery of viral antigens and TLR4 and 9 agonists which induce activation of innate immune signatures and promote potent antigen acquisition and cross-presentation by multiple DC subsets. PMID:24463331

  6. Modular biowaste monitoring system

    NASA Technical Reports Server (NTRS)

    Fogal, G. L.

    1975-01-01

    The objective of the Modular Biowaste Monitoring System Program was to generate and evaluate hardware for supporting shuttle life science experimental and diagnostic programs. An initial conceptual design effort established requirements and defined an overall modular system for the collection, measurement, sampling and storage of urine and feces biowastes. This conceptual design effort was followed by the design, fabrication and performance evaluation of a flight prototype model urine collection, volume measurement and sampling capability. No operational or performance deficiencies were uncovered as a result of the performance evaluation tests.

  7. Criteria for software modularization

    NASA Technical Reports Server (NTRS)

    Card, David N.; Page, Gerald T.; Mcgarry, Frank E.

    1985-01-01

    A central issue in programming practice involves determining the appropriate size and information content of a software module. This study attempted to determine the effectiveness of two widely used criteria for software modularization, strength and size, in reducing fault rate and development cost. Data from 453 FORTRAN modules developed by professional programmers were analyzed. The results indicated that module strength is a good criterion with respect to fault rate, whereas arbitrary module size limitations inhibit programmer productivity. This analysis is a first step toward defining empirically based standards for software modularization.

  8. The Evolution of Modular Construction.

    ERIC Educational Resources Information Center

    American School & University, 1993

    1993-01-01

    Explores how the myths of modular construction for schools began; also discusses the advances made in steel and modular construction. The major advantages of using permanent modular construction for schools are highlighted, including its rapid construction, use of standard building materials, financial flexibility, and durability. (GR)

  9. State Librarianship: Modular Curriculum.

    ERIC Educational Resources Information Center

    Robbins, Jane; Powell, Anne

    This modular curriculum on state librarianship is designed to be used as a basis for a full-length library science course, instructional segments of several courses, continuing education courses, or workshops. The 20 curriculum modules cover the many facets of state libraries and their activities--history, functions, social and political…

  10. Modular invariant inflation

    NASA Astrophysics Data System (ADS)

    Kobayashi, Tatsuo; Nitta, Daisuke; Urakawa, Yuko

    2016-08-01

    Modular invariance is a striking symmetry in string theory, which may keep stringy corrections under control. In this paper, we investigate a phenomenological consequence of the modular invariance, assuming that this symmetry is preserved as well as in a four dimensional (4D) low energy effective field theory. As a concrete setup, we consider a modulus field T whose contribution in the 4D effective field theory remains invariant under the modular transformation and study inflation drived by T. The modular invariance restricts a possible form of the scalar potenntial. As a result, large field models of inflation are hardly realized. Meanwhile, a small field model of inflation can be still accomodated in this restricted setup. The scalar potential traced during the slow-roll inflation mimics the hilltop potential Vht, but it also has a non-negligible deviation from Vht. Detecting the primordial gravitational waves predicted in this model is rather challenging. Yet, we argue that it may be still possible to falsify this model by combining the information in the reheating process which can be determined self-completely in this setup.

  11. Modularity in robotic systems

    NASA Technical Reports Server (NTRS)

    Tesar, Delbert; Butler, Michael S.

    1989-01-01

    Most robotic systems today are designed one at a time, at a high cost of time and money. This wasteful approach has been necessary because the industry has not established a foundation for the continued evolution of intelligent machines. The next generation of robots will have to be generic, versatile machines capable of absorbing new technology rapidly and economically. This approach is demonstrated in the success of the personal computer, which can be upgraded or expanded with new software and hardware at virtually every level. Modularity is perceived as a major opportunity to reduce the 6 to 7 year design cycle time now required for new robotic manipulators, greatly increasing the breadth and speed of diffusion of robotic systems in manufacturing. Modularity and its crucial role in the next generation of intelligent machines are the focus of interest. The main advantages that modularity provides are examined; types of modules needed to create a generic robot are discussed. Structural modules designed by the robotics group at the University of Texas at Austin are examined to demonstrate the advantages of modular design.

  12. Modular Perspectives on Bilingualism.

    ERIC Educational Resources Information Center

    Francis, Norbert

    2002-01-01

    This research review traces the current discussion on models of bilingualism to the contributions of Vygotsky and Luria. Proposes that a modular approach to studying the different aspects of bilingual development promises to chart a course toward finding a broader common ground around research findings and interpretations that appear to be…

  13. MRV - Modular Robotic Vehicle

    NASA Technical Reports Server (NTRS)

    Ridley, Justin; Bluethmann, Bill

    2015-01-01

    The Modular Robotic Vehicle, or MRV, completed in 2013, was developed at the Johnson Space Center in order to advance technologies which have applications for future vehicles both in space and on Earth. With seating for two people, MRV is a fully electric vehicle modeled as a "city car", suited for busy urban environments.

  14. The Impact of Multifunctional Genes on "Guilt by Association" Analysis

    PubMed Central

    Gillis, Jesse; Pavlidis, Paul

    2011-01-01

    Many previous studies have shown that by using variants of “guilt-by-association”, gene function predictions can be made with very high statistical confidence. In these studies, it is assumed that the “associations” in the data (e.g., protein interaction partners) of a gene are necessary in establishing “guilt”. In this paper we show that multifunctionality, rather than association, is a primary driver of gene function prediction. We first show that knowledge of the degree of multifunctionality alone can produce astonishingly strong performance when used as a predictor of gene function. We then demonstrate how multifunctionality is encoded in gene interaction data (such as protein interactions and coexpression networks) and how this can feed forward into gene function prediction algorithms. We find that high-quality gene function predictions can be made using data that possesses no information on which gene interacts with which. By examining a wide range of networks from mouse, human and yeast, as well as multiple prediction methods and evaluation metrics, we provide evidence that this problem is pervasive and does not reflect the failings of any particular algorithm or data type. We propose computational controls that can be used to provide more meaningful control when estimating gene function prediction performance. We suggest that this source of bias due to multifunctionality is important to control for, with widespread implications for the interpretation of genomics studies. PMID:21364756

  15. Pirin1 (PRN1) Is a Multifunctional Protein that Regulates Quercetin, and Impacts Specific Light and UV Responses in the Seed-to-Seedling Transition of Arabidopsis thaliana

    PubMed Central

    Orozco-Nunnelly, Danielle A.; Muhammad, DurreShahwar; Mezzich, Raquel; Lee, Bao-Shiang; Jayathilaka, Lasanthi; Kaufman, Lon S.; Warpeha, Katherine M.

    2014-01-01

    Pirins are cupin-fold proteins, implicated in apoptosis and cellular stress in eukaryotic organisms. Pirin1 (PRN1) plays a role in seed germination and transcription of a light- and ABA-regulated gene under specific conditions in the model plant system Arabidopsis thaliana. Herein, we describe that PRN1 possesses previously unreported functions that can profoundly affect early growth, development, and stress responses. In vitro-translated PRN1 possesses quercetinase activity. When PRN1 was incubated with G-protein-α subunit (GPA1) in the inactive conformation (GDP-bound), quercetinase activity was observed. Quercetinase activity was not observed when PRN1 was incubated with GPA1 in the active form (GTP-bound). Dark-grown prn1 mutant seedlings produced more quercetin after UV (317 nm) induction, compared to levels observed in wild type (WT) seedlings. prn1 mutant seedlings survived a dose of high-energy UV (254 nm) radiation that killed WT seedlings. prn1 mutant seedlings grown for 3 days in continuous white light display disoriented hypocotyl growth compared to WT, but hypocotyls of dark-grown prn1 seedlings appeared like WT. prn1 mutant seedlings transformed with GFP constructs containing the native PRN1 promoter and full ORF (PRN1::PRN1-GFP) were restored to WT responses, in that they did not survive UV (254 nm), and there was no significant hypocotyl disorientation in response to white light. prn1 mutants transformed with PRN1::PRN1-GFP were observed by confocal microscopy, where expression in the cotyledon epidermis was largely localized to the nucleus, adjacent to the nucleus, and diffuse and punctate expression occurred within some cells. WT seedlings transformed with the 35S::PRN1-GFP construct exhibited widespread expression in the epidermis of the cotyledon, also with localization in the nucleus. PRN1 may play a critical role in cellular quercetin levels and influence light- or hormonal-directed early development. PMID:24705271

  16. Diffusible signal factor (DSF) synthase RpfF of Xylella fastidiosa is a multifunction protein also required for response to DSF.

    PubMed

    Ionescu, Michael; Baccari, Clelia; Da Silva, Aline Maria; Garcia, Angelica; Yokota, Kenji; Lindow, Steven E

    2013-12-01

    Xylella fastidiosa, like related Xanthomonas species, employs an Rpf cell-cell communication system consisting of a diffusible signal factor (DSF) synthase, RpfF, and a DSF sensor, RpfC, to coordinate expression of virulence genes. While phenotypes of a ΔrpfF strain in Xanthomonas campestris could be complemented by its own DSF, the DSF produced by X. fastidiosa (XfDSF) did not restore expression of the XfDSF-dependent genes hxfA and hxfB to a ΔrpfF strain of X. fastidiosa, suggesting that RpfF is involved in XfDSF sensing or XfDSF-dependent signaling. To test this conjecture, rpfC and rpfF of X. campestris were replaced by those of X. fastidiosa, and the contribution of each gene to the induction of a X. campestris DSF-dependent gene was assessed. As in X. fastidiosa, XfDSF-dependent signaling required both X. fastidiosa proteins RpfF and RpfC. RpfF repressed RpfC signaling activity, which in turn was derepressed by XfDSF. A mutated X. fastidiosa RpfF protein with two substitutions of glutamate to alanine in its active site was incapable of XfDSF production yet enabled a response to XfDSF, indicating that XfDSF production and the response to XfDSF are two separate functions in which RpfF is involved. This mutant was also hypervirulent to grape, demonstrating the antivirulence effects of XfDSF itself in X. fastidiosa. The Rpf system of X. fastidiosa is thus a novel example of a quorum-sensing signal synthase that is also involved in the response to the signal molecule that it synthesizes. PMID:24056101

  17. Multifunctional Thin Film Biomatrice Biosensor in a Degradable Scaffold Containing Bone Morphogenetic Protein-2 (BMP-2) for Controlled Release in Skeletal Tissue Engineering

    NASA Astrophysics Data System (ADS)

    McDaniel, Harvey; Lomax, Linda

    2001-03-01

    Bone morphonogenetic proteins (BMP-2) have been under investigation for three decades. Deminerialized bone and extracts of deminerialized bone are o steoinductive with a temporal sequence of bone induction. Native and recombi nant BMP's have shown the ability, thru growth and differentiative factors t o induce de novo bone formation both invitro and invivo. Their principle fun ction is to induce transformation of undifferentiated mesenchymal cells into osteoblasts. Native and recombinant BMP's, when purified and used without carrier disp erse after implantation and exert no effect on bone induction. The delivery system provides the missing component to successsfully applying osteogenic p roteins for clinical need. Biological and physio-chemical properties are str ictly adhered tofor a successful delivery system. The BMP delivery system ca rrier for osteo inductive payload provided; 1)non tumorgenic genecity, 2) no n immunogenecity, 3) water insoluble, 4) biosorbability with predictable enz ymatic degradation, and 5) an optimized surface for compatibility, cell migr ation and attachment with a negative surface change that encouraged target c ell attachment. Being a controlled Release System, it binded the proteins wi th predictible BMP released kinetics. Porosity with interconnecting voids pr otected the BMP from noon specific proteolysis and promoted rapid vascular a nd mesenchymal invasion. Far wide ranging clinical applications of mechanica l and biofunctional requirements were met with the BMP delivery system. Cohe sion and malleability were reqiured forcontour augmentation, and reconstruct ion of the discontinuity defects, prevented dislocation and retained the sha pe and bone replaced the system. Biological systems have elastic activity associated with them. The activi ty was current associated with a time dependant biological/biochemical react ion (enzymic activity). Bioelectric phoenomena associated with charged molec ules in a biologic structure caused

  18. The multi-functional sorting protein PACS-2 regulates SIRT1-mediated deacetylation of p53 to modulate p21-dependent cell cycle arrest

    PubMed Central

    Atkins, Katelyn M.; Thomas, Laura L.; Barroso-González, Jonathan; Thomas, Laurel; Auclair, Sylvain; Yin, Jun; Kang, Hyeog; Chung, Jay H.; Dikeakos, Jimmy D.; Thomas, Gary

    2014-01-01

    SUMMARY SIRT1 regulates the DNA damage response by deacetylating p53, thereby repressing p53 transcriptional output. Here we demonstrate that the sorting protein PACS-2 regulates SIRT1-mediated deacetylation of p53 to modulate the DNA damage response. PACS-2 knockdown cells failed to efficiently undergo p53-induced cell cycle arrest in response to DNA damage. Accordingly, p53 acetylation was reduced both in PACS-2 knockdown cells and thymocytes from Pacs-2−/− mice, thereby blunting induction of the cyclin-dependent kinase inhibitor p21 (CDKN1A). The SIRT1 inhibitor EX-527 or SIRT1 knockdown restored p53 acetylation and p21 induction as well as p21-dependent cell cycle arrest in PACS-2 knockdown cells. Trafficking studies revealed cytoplasmic PACS-2 shuttled to the nucleus where it interacted with SIRT1 and repressed SIRT1-mediated p53 deacetylation. Correspondingly, in vitro assays demonstrated PACS-2 directly inhibited SIRT1-catalyzed p53 deacetylation. Together, these findings identify PACS-2 as an in vivo mediator of the SIRT1—p53—p21 axis that modulates the DNA damage response. PMID:25159152

  19. Identification of multifunctional peptides from human milk.

    PubMed

    Mandal, Santi M; Bharti, Rashmi; Porto, William F; Gauri, Samiran S; Mandal, Mahitosh; Franco, Octavio L; Ghosh, Ananta K

    2014-06-01

    Pharmaceutical industries have renewed interest in screening multifunctional bioactive peptides as a marketable product in health care applications. In this context, several animal and plant peptides with potential bioactivity have been reported. Milk proteins and peptides have received much attention as a source of health-enhancing components to be incorporated into nutraceuticals and functional foods. By using this source, 24 peptides have been fractionated and purified from human milk using RP-HPLC. Multifunctional roles including antimicrobial, antioxidant and growth stimulating activity have been evaluated in all 24 fractions. Nevertheless, only four fractions show multiple combined activities among them. Using a proteomic approach, two of these four peptides have been identified as lactoferrin derived peptide and kappa casein short chain peptide. Lactoferrin derived peptide (f8) is arginine-rich and kappa casein derived (f12) peptide is proline-rich. Both peptides (f8 and f12) showed antimicrobial activities against both Gram-positive and Gram-negative bacteria. Fraction 8 (f8) exhibits growth stimulating activity in 3T3 cell line and f12 shows higher free radical scavenging activity in comparison to other fractions. Finally, both peptides were in silico evaluated and some insights into their mechanism of action were provided. Thus, results indicate that these identified peptides have multiple biological activities which are valuable for the quick development of the neonate and may be considered as potential biotechnological products for nutraceutical industry. PMID:24703967

  20. Multi-functional composite structures

    DOEpatents

    Mulligan, Anthony C.; Halloran, John; Popovich, Dragan; Rigali, Mark J.; Sutaria, Manish P.; Vaidyanathan, K. Ranji; Fulcher, Michael L.; Knittel, Kenneth L.

    2010-04-27

    Fibrous monolith processing techniques to fabricate multifunctional structures capable of performing more than one discrete function such as structures capable of bearing structural loads and mechanical stresses in service and also capable of performing at least one additional non-structural function.

  1. Multi-functional composite structures

    DOEpatents

    Mulligan, Anthony C.; Halloran, John; Popovich, Dragan; Rigali, Mark J.; Sutaria, Manish P.; Vaidyanathan, K. Ranji; Fulcher, Michael L.; Knittel, Kenneth L.

    2004-10-19

    Fibrous monolith processing techniques to fabricate multifunctional structures capable of performing more than one discrete function such as structures capable of bearing structural loads and mechanical stresses in service and also capable of performing at least one additional non-structural function.

  2. Modular integrated video system

    SciTech Connect

    Gaertner, K.J.; Heaysman, B.; Holt, R.; Sonnier, C.

    1986-01-01

    The Modular Integrated Video System (MIVS) is intended to provide a simple, highly reliable closed circuit television (CCTV) system capable of replacing the IAEA Twin Minolta Film Camera Systems in those safeguards facilities where mains power is readily available, and situations where it is desired to have the CCTV camera separated from the CCTV recording console. This paper describes the MIVS and the Program Plan which is presently being followed for the development, testing, and implementation of the system.

  3. Multifunctional reactive nanocomposite materials

    NASA Astrophysics Data System (ADS)

    Stamatis, Demitrios

    Many multifunctional nanocomposite materials have been developed for use in propellants, explosives, pyrotechnics, and reactive structures. These materials exhibit high reaction rates due to their developed reaction interfacial area. Two applications addressed in this work include nanocomposite powders prepared by arrested reactive milling (ARM) for burn rate modifiers and reactive structures. In burn rate modifiers, addition of reactive nanocomposite powders to aluminized propellants increases the burn rate of aluminum and thus the overall reaction rate of an energetic formulation. Replacing only a small fraction of aluminum by 8Al·MoO3 and 2B·Ti nanocomposite powders enhances the reaction rate with little change to the thermodynamic performance of the formulation; both the rate of pressure rise and maximum pressure measured in the constant volume explosion test increase. For reactive structures, nanocomposite powders with bulk compositions of 8Al·MoO3, 12Al·MoO3, and 8Al·3CuO were prepared by ARM and consolidated using a uniaxial die. Consolidated samples had densities greater than 90% of theoretical maximum density while maintaining their high reactivity. Pellets prepared using 8Al·MoO3 powders were ignited by a CO2 laser. Ignition delays increased at lower laser powers and greater pellet densities. A simplified numerical model describing heating and thermal initiation of the reactive pellets predicted adequately the observed effects of both laser power and pellet density on the measured ignition delays. To investigate the reaction mechanisms in nanocomposite thermites, two types of nanocomposite reactive materials with the same bulk compositions 8Al·MoO3 were prepared by different methods. One of the materials was manufactured by ARM and the other, so called metastable interstitial composite (MIC), by mixing of nano-scaled individual powders. Clear differences in the low-temperature redox reactions, welldetectable by differential scanning calorimetry

  4. Nucleolin: a multifunctional major nucleolar phosphoprotein.

    PubMed

    Tuteja, R; Tuteja, N

    1998-01-01

    Nucleolin is a major protein of exponentially growing eukaryotic cells where it is present in abundance at the heart of the nucleolus. It is highly conserved during evolution. Nucleolin contains a specific bipartite nuclear localization signal sequence and possesses a number of unusual structural features. It has unique tripartite structure and each domain performs a specific function by interacting with DNA or RNA or proteins. Nucleolin exhibits intrinsic self-cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities. Nucleolin also acts as a sequence-specific RNA binding protein, an autoantigen, and as the component of a B cell specific transcription factor. Its phosphorylation by cdc2, CK2, and PKC-zeta modulate some of its activities. This multifunctional protein has been implicated to be involved directly or indirectly in many metabolic processes such as ribosome biogenesis (which includes rDNA transcription, pre-rRNA synthesis, rRNA processing, ribosomal assembly and maturation), cytokinesis, nucleogenesis, cell proliferation and growth, cytoplasmic-nucleolar transport of ribosomal components, transcriptional repression, replication, signal transduction, inducing chromatin decondensation and many more (see text). In plants it is developmentally, cell-cycle, and light regulated. The regulation of all these functions of a single protein seems to be a challenging puzzle. PMID:9918513

  5. Modularity enhances the rate of evolution in a rugged fitness landscape

    NASA Astrophysics Data System (ADS)

    Park, Jeong-Man; Chen, Man; Wang, Dong; Deem, Michael W.

    2015-04-01

    Biological systems are modular, and this modularity affects the evolution of biological systems over time and in different environments. We here develop a theory for the dynamics of evolution in a rugged, modular fitness landscape. We show analytically how horizontal gene transfer couples to the modularity in the system and leads to more rapid rates of evolution at short times. The model, in general, analytically demonstrates a selective pressure for the prevalence of modularity in biology. We use this model to show how the evolution of the influenza virus is affected by the modularity of the proteins that are recognized by the human immune system. Approximately 25% of the observed rate of fitness increase of the virus could be ascribed to a modular viral landscape.

  6. Modularity Enhances the Rate of Evolution in a Rugged Fitness Landscape

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Park, Jeong-Man; Chen, Man; Deem, Michael

    2015-03-01

    Biological systems are modular, and this modularity affects the evolution of biological systems over time and in different environments. We here develop a theory for the dynamics of evolution in a rugged, modular fitness landscape. We show analytically how horizontal gene transfer couples to the modularity in the system and leads to more rapid rates of evolution at short times. The model, in general, analytically demonstrates a selective pressure for the prevalence of modularity in biology. We use this model to show how the evolution of the influenza virus is affected by the modularity of the proteins that are recognized by the human immune system. A modular model of the fitness landscape of the virus better fits the observed virus evolution data. This research was supported by the US National Institutes of Health under Grant 1 R01 GM 100468-01. JMP was also supported by the National Research Foundation of Korea Grant (NRF-2013R1A1A2006983).

  7. Modularity Enhances the Rate of Evolution in a Rugged Fitness Landscape

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Park, Jeong-Man; Chen, Man; Deem, Michael

    Biological systems are modular, and this modularity affects the evolution of biological systems over time and in different environments. We here develop a theory for the dynamics of evolution in a rugged, modular fitness landscape. We show analytically how horizontal gene transfer couples to the modularity in the system and leads to more rapid rates of evolution at short times. The model, in general, analytically demonstrates a selective pressure for the prevalence of modularity in biology. We use this model to show how the evolution of the influenza virus is affected by the modularity of the proteins that are recognized by the human immune system. A modular model of the fitness landscape of the virus better fits the observed virus evolution data.

  8. New realities of modular construction

    SciTech Connect

    Duty, J.M. Jr. ); Fisher, D. ); Lewis, W.W. )

    1993-12-01

    Modular construction has both advantages and disadvantages. Advantages are safety, reduction of construction time and faster plant startup time, reduced labor cost, weather friendliness, increased quality and efficiency, simultaneous production capability, testing ease and fewer interruptions to an operating plant. Disadvantages are transportation costs, module size limitations, transportation-accessibility needs, increased engineering effort, and offloading and setting needs. These pros and cons were identified by a Construction Industry Institute (C2) task force established in 1989 to assess modular construction strengths and weaknesses. Objective: develop a decision-support tool to evaluate a project's suitability for modularization. The task force first had to learn what drivers influence modularization and then develop a set of characteristics of the ideal project for modularization. To help in this research, academics from the University of Houston and Purdue University developed MODEX, an expert system which became the decision-support tool. The paper first discusses the myths of modularization and then describes MODEX.

  9. Multifunctional RNA Nanoparticles

    PubMed Central

    2015-01-01

    Our recent advancements in RNA nanotechnology introduced novel nanoscaffolds (nanorings); however, the potential of their use for biomedical applications was never fully revealed. As presented here, besides functionalization with multiple different short interfering RNAs for combinatorial RNA interference (e.g., against multiple HIV-1 genes), nanorings also allow simultaneous embedment of assorted RNA aptamers, fluorescent dyes, proteins, as well as recently developed RNA–DNA hybrids aimed to conditionally activate multiple split functionalities inside cells. PMID:25267559

  10. Robotic hand with modular extensions

    DOEpatents

    Salisbury, Curt Michael; Quigley, Morgan

    2015-01-20

    A robotic device is described herein. The robotic device includes a frame that comprises a plurality of receiving regions that are configured to receive a respective plurality of modular robotic extensions. The modular robotic extensions are removably attachable to the frame at the respective receiving regions by way of respective mechanical fuses. Each mechanical fuse is configured to trip when a respective modular robotic extension experiences a predefined load condition, such that the respective modular robotic extension detaches from the frame when the load condition is met.

  11. Effective Design of Multifunctional Peptides by Combining Compatible Functions

    PubMed Central

    Diener, Christian; Garza Ramos Martínez, Georgina; Moreno Blas, Daniel; Castillo González, David A.; Corzo, Gerardo; Castro-Obregon, Susana; Del Rio, Gabriel

    2016-01-01

    Multifunctionality is a common trait of many natural proteins and peptides, yet the rules to generate such multifunctionality remain unclear. We propose that the rules defining some protein/peptide functions are compatible. To explore this hypothesis, we trained a computational method to predict cell-penetrating peptides at the sequence level and learned that antimicrobial peptides and DNA-binding proteins are compatible with the rules of our predictor. Based on this finding, we expected that designing peptides for CPP activity may render AMP and DNA-binding activities. To test this prediction, we designed peptides that embedded two independent functional domains (nuclear localization and yeast pheromone activity), linked by optimizing their composition to fit the rules characterizing cell-penetrating peptides. These peptides presented effective cell penetration, DNA-binding, pheromone and antimicrobial activities, thus confirming the effectiveness of our computational approach to design multifunctional peptides with potential therapeutic uses. Our computational implementation is available at http://bis.ifc.unam.mx/en/software/dcf. PMID:27096600

  12. Transglutaminase type 2: A multifunctional protein chaperone?

    PubMed Central

    Rossin, Federica; D’Eletto, Manuela; Farrace, Maria Grazia; Piacentini, Mauro

    2014-01-01

    Macroautophagy selectively degrades dysfunctional mitochondria by a process known as mitophagy. The purpose of the study published in Cell Death and Differentiation was to investigate the involvement of transglutaminase 2 (TG2) in the turnover and degradation of damaged mitochondria and its effects on cell metabolism. PMID:27308365

  13. Studies in Multifunctional Drug Development: Preparation and Evaluation of 11beta-Substituted Estradiol-Drug Conjugates, Cell Membrane Targeting Imaging Agents, and Target Multifunctional Nanoparticles

    NASA Astrophysics Data System (ADS)

    Dao, KinhLuan Lenny D.

    Cancer is the second leading cause of death after cardiovascular disease in the United State. Despite extensive research in development of antitumor drugs, most of these therapeutic entities often possess nonspecific toxicity, thus they can only be used to treat tumors in higher doses or more frequently. Because of the cytotoxicity and severe side effects, the drug therapeutic window normally is limited. Beside the toxicity issue, antitumor drug are also not selectively taken up by tumor cells, thus the necessitating concentrations that would eradicate the tumor can often not be used. In addition, tumor cells tend to develop resistance against the anticancer drugs after prolonged treatment. Therefore, alleviating the systemic cytotoxicity and side effects, improving in tumor selectivity, high potency, and therapeutic efficacy are still major obstacles in the area of anticancer drug development. A more promising approach for developing a selective agent for cancer is to conjugate a potent therapeutic drug, or an imaging agent with a targeting group, such as antibody or a high binding-specificity small molecule, that selectively recognize the overexpressed antigens or proteins on tumor cells. My research combines several approaches to describe this strategy via using different targeting molecules to different diseases, as well as different potent cytotoxic drugs for different therapies. Three studies related to the preparation and biological evaluation of new therapeutic agents, such as estradiol-drug hybrids, cell membrane targeted molecular imaging agents, and multifunctional NPs will be discussed. The preliminary results of these studies indicated that our new reagents achieved their initial objectives and can be further improved for optimized synthesis and in vivo experiments. The first study describes the method in which we employed a modular assembly approach to synthesize a novel 11beta-substituted steroidal anti-estrogen. The key intermediate was synthesized

  14. Multifunctional nanoparticles for cancer immunotherapy.

    PubMed

    Saleh, Tayebeh; Shojaosadati, Seyed Abbas

    2016-07-01

    During the last decades significant progress has been made in the field of cancer immunotherapy. However, cancer vaccines have not been successful in clinical trials due to poor immunogenicity of antigen, limitations of safety associated with traditional systemic delivery as well as the complex regulation of the immune system in tumor microenvironment. In recent years, nanotechnology-based delivery systems have attracted great interest in the field of immunotherapy since they provide new opportunities to fight the cancer. In particular, for delivery of cancer vaccines, multifunctional nanoparticles present many advantages such as targeted delivery to immune cells, co-delivery of therapeutic agents, reduced adverse outcomes, blocked immune checkpoint molecules, and amplify immune activation via the use of stimuli-responsive or immunostimulatory materials. In this review article, we highlight recent progress and future promise of multifunctional nanoparticles that have been applied to enhance the efficiency of cancer vaccines. PMID:26901287

  15. Modular biometric system

    NASA Astrophysics Data System (ADS)

    Hsu, Charles; Viazanko, Michael; O'Looney, Jimmy; Szu, Harold

    2009-04-01

    Modularity Biometric System (MBS) is an approach to support AiTR of the cooperated and/or non-cooperated standoff biometric in an area persistent surveillance. Advanced active and passive EOIR and RF sensor suite is not considered here. Neither will we consider the ROC, PD vs. FAR, versus the standoff POT in this paper. Our goal is to catch the "most wanted (MW)" two dozens, separately furthermore ad hoc woman MW class from man MW class, given their archrivals sparse front face data basis, by means of various new instantaneous input called probing faces. We present an advanced algorithm: mini-Max classifier, a sparse sample realization of Cramer-Rao Fisher bound of the Maximum Likelihood classifier that minimize the dispersions among the same woman classes and maximize the separation among different man-woman classes, based on the simple feature space of MIT Petland eigen-faces. The original aspect consists of a modular structured design approach at the system-level with multi-level architectures, multiple computing paradigms, and adaptable/evolvable techniques to allow for achieving a scalable structure in terms of biometric algorithms, identification quality, sensors, database complexity, database integration, and component heterogenity. MBS consist of a number of biometric technologies including fingerprints, vein maps, voice and face recognitions with innovative DSP algorithm, and their hardware implementations such as using Field Programmable Gate arrays (FPGAs). Biometric technologies and the composed modularity biometric system are significant for governmental agencies, enterprises, banks and all other organizations to protect people or control access to critical resources.

  16. Complex modular structure of large-scale brain networks

    NASA Astrophysics Data System (ADS)

    Valencia, M.; Pastor, M. A.; Fernández-Seara, M. A.; Artieda, J.; Martinerie, J.; Chavez, M.

    2009-06-01

    Modular structure is ubiquitous among real-world networks from related proteins to social groups. Here we analyze the modular organization of brain networks at a large scale (voxel level) extracted from functional magnetic resonance imaging signals. By using a random-walk-based method, we unveil the modularity of brain webs and show modules with a spatial distribution that matches anatomical structures with functional significance. The functional role of each node in the network is studied by analyzing its patterns of inter- and intramodular connections. Results suggest that the modular architecture constitutes the structural basis for the coexistence of functional integration of distant and specialized brain areas during normal brain activities at rest.

  17. Multifunctional nanocomposite materials. Progress report

    SciTech Connect

    Roy, R.; Komarneni, S.

    1991-11-01

    Objective is to examine the low temperature nanocomposite route in the synthesis of multifunctional materials using two-dimensional clays as hosts. After about 8 months, a significant advance was made in the design and synthesis of novel nanocomposite materials, which are nanometal intercalated clays prepared by a low temperature route. A layered V{sub 2}O{sub 5} gel has been made hydrothermally and its cation exchange properties measured. Several pillared clays have also been synthesized and characterized.

  18. Modular gear bearings

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor)

    2009-01-01

    A gearing system using modular gear bearing components. Each component is composed of a core, one or more modules attached to the core and two or more fastening modules rigidly attaching the modules to the core. The modules, which are attached to the core, may consist of gears, rollers or gear bearing components. The core orientation affects the orientation of the modules attached to the core. This is achieved via the keying arrangement of the core and the component modules that attach to the core. Such an arrangement will also facilitate the phase tuning of gear modules with respect to the core and other gear modules attached to the core.

  19. Modular space station facilities.

    NASA Technical Reports Server (NTRS)

    Parker, P. J.

    1973-01-01

    The modular space station will operate as a general purpose laboratory (GPL). In addition, the space station will be able to support many attached or free-flying research and application modules that would be dedicated to specific projects like astronomy or earth observations. The GPL primary functions have been organized into functional laboratories including an electrical/electronics laboratory, a mechanical sciences laboratory, an experiment and test isolation laboratory, a hard data process facility, a data evaluation facility, an optical sciences laboratory, a biomedical and biosciences laboratory, and an experiment/secondary command and control center.

  20. MUC16/CA125 in the Context of Modular Proteins with an Annotated Role in Adhesion-Related Processes: In Silico Analysis

    PubMed Central

    Jankovic, Miroslava; Mitic, Ninoslav

    2012-01-01

    Mucin 16 (MUC16) is a type I transmembrane protein, the extracellular portion of which is shed after proteolytic degradation and is denoted as CA125 antigen, a well known tumor marker for ovarian cancer. Regarding its polypeptide and glycan structures, as yet there is no detailed insight into their heterogeneity and ligand properties, which may greatly influence its function and biomarker potential. This study was aimed at obtaining further insight into the biological capacity of MUC16/CA125, using in silico analysis of corresponding mucin sequences, including similarity searches as well as GO (gene ontology)-based function prediction. The results obtained pointed to the similarities within extracellular serine/threonine rich regions of MUC16 to sequences of proteins expressed in evolutionary distant taxa, all having in common an annotated role in adhesion-related processes. Specifically, a homology to conserved domains from the family of herpesvirus major outer envelope protein (BLLF1) was found. In addition, the possible involvement of MUC16/CA125 in carbohydrate-binding interactions or cellular transport of protein/ion was suggested. PMID:22949868

  1. Implantable, multifunctional, bioresorbable optics

    PubMed Central

    Tao, Hu; Kainerstorfer, Jana M.; Siebert, Sean M.; Pritchard, Eleanor M.; Sassaroli, Angelo; Panilaitis, Bruce J. B.; Brenckle, Mark A.; Amsden, Jason J.; Levitt, Jonathan; Fantini, Sergio; Kaplan, David L.; Omenetto, Fiorenzo G.

    2012-01-01

    Advances in personalized medicine are symbiotic with the development of novel technologies for biomedical devices. We present an approach that combines enhanced imaging of malignancies, therapeutics, and feedback about therapeutics in a single implantable, biocompatible, and resorbable device. This confluence of form and function is accomplished by capitalizing on the unique properties of silk proteins as a mechanically robust, biocompatible, optically clear biomaterial matrix that can house, stabilize, and retain the function of therapeutic components. By developing a form of high-quality microstructured optical elements, improved imaging of malignancies and of treatment monitoring can be achieved. The results demonstrate a unique family of devices for in vitro and in vivo use that provide functional biomaterials with built-in optical signal and contrast enhancement, demonstrated here with simultaneous drug delivery and feedback about drug delivery with no adverse biological effects, all while slowly degrading to regenerate native tissue. PMID:23150544

  2. Modular reflector concept study

    NASA Technical Reports Server (NTRS)

    Vaughan, D. H.

    1981-01-01

    A study was conducted to evaluate the feasibility of space erecting a 100 meter paraboloidal radio frequency reflector by joining a number of individually deployed structural modules. Three module design concepts were considered: (1) the deployable cell module (DCM); (2) the modular paraboloidal erectable truss antenna (Mod-PETA); and (3) the modular erectable truss antenna (META). With the space shuttle (STS) as the launch system, the methodology of packaging and stowing in the orbiter, and of dispensing, deploying and joining, in orbit, were studied and the necessary support equipment identified. The structural performance of the completed reflectors was evaluated and their overall operational capability and feasibility were evaluated and compared. The potential of the three concepts to maintain stable shape in the space environment was determined. Their ability to operate at radio frequencies of 1 GHz and higher was assessed assuming the reflector surface to consist of a number of flat, hexagonal facets. A parametric study was performed to determine figure degradation as a function of reflector size, flat facet size, and f/D ratio.

  3. Modular robotic architecture

    NASA Astrophysics Data System (ADS)

    Smurlo, Richard P.; Laird, Robin T.

    1991-03-01

    The development of control architectures for mobile systems is typically a task undertaken with each new application. These architectures address different operational needs and tend to be difficult to adapt to more than the problem at hand. The development of a flexible and extendible control system with evolutionary growth potential for use on mobile robots will help alleviate these problems and if made widely available will promote standardization and cornpatibility among systems throughout the industry. The Modular Robotic Architecture (MRA) is a generic control systern that meets the above needs by providing developers with a standard set of software hardware tools that can be used to design modular robots (MODBOTs) with nearly unlimited growth potential. The MODBOT itself is a generic creature that must be customized by the developer for a particular application. The MRA facilitates customization of the MODBOT by providing sensor actuator and processing modules that can be configured in almost any manner as demanded by the application. The Mobile Security Robot (MOSER) is an instance of a MODBOT that is being developed using the MRA. Navigational Sonar Module RF Link Control Station Module hR Link Detection Module Near hR Proximi Sensor Module Fluxgate Compass and Rate Gyro Collision Avoidance Sonar Module Figure 1. Remote platform module configuration of the Mobile Security Robot (MOSER). Acoustical Detection Array Stereoscopic Pan and Tilt Module High Level Processing Module Mobile Base 566

  4. Modular antenna design study

    NASA Technical Reports Server (NTRS)

    Ribble, J. W.

    1981-01-01

    The mechanical design of a modular antenna concept was developed sufficiently to allow manufacture of a working demonstration model of a module, to predict mass properties, and to make performance estimates for antenna reflectors composed of these modules. The primary features of this concept are: (1) each module is an autonomous structural element which can be attached to adjacent modules through a three point connection; (2) the upper surface is a folding hexagonal truss plate mechanism which serves as the supporting structure for a reflective surface; and (3) the entire truss and surface can be folded into a cylindrical envelope in which all truss elements are essentially parallel. The kinematic studies and engineering demonstration model fully verified the deployment kinematics, stowing philosophy, and deployment sequencing for large antenna modules. It was established that such modules can be stowed in packages as small as 25 cm in diameter, using 1.27 cm diameter structural tubes. The development activity indicates that this deployable modular approach towards building large structures in space will support erection of 450 m apertures for operation up to 3 GHz with a single space shuttle flight.

  5. Modular radiochemistry synthesis system

    SciTech Connect

    Satyamurthy, Nagichettiar; Barrio, Jorge R; Amarasekera, Bernard; Van Dam, R. Michael; Olma, Sebastian; Williams, Dirk; Eddings, Mark A; Shen, Clifton Kwang-Fu

    2015-02-10

    A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

  6. Modular radiochemistry synthesis system

    SciTech Connect

    Satyamurthy, Nagichettiar; Barrio, Jorge R.; Amarasekera, Bernard; Van Dam, R. Michael; Olma, Sebastian; Williams, Dirk; Eddings, Mark; Shen, Clifton Kwang-Fu

    2015-12-15

    A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

  7. Modular Robotic Vehicle

    NASA Technical Reports Server (NTRS)

    Borroni-Bird, Christopher E. (Inventor); Vitale, Robert L. (Inventor); Lee, Chunhao J. (Inventor); Ambrose, Robert O. (Inventor); Bluethmann, William J. (Inventor); Junkin, Lucien Q. (Inventor); Lutz, Jonathan J. (Inventor); Guo, Raymond (Inventor); Lapp, Anthony Joseph (Inventor); Ridley, Justin S. (Inventor)

    2015-01-01

    A modular robotic vehicle includes a chassis, driver input devices, an energy storage system (ESS), a power electronics module (PEM), modular electronic assemblies (eModules) connected to the ESS via the PEM, one or more master controllers, and various embedded controllers. Each eModule includes a drive wheel containing a propulsion-braking module, and a housing containing propulsion and braking control assemblies with respective embedded propulsion and brake controllers, and a mounting bracket covering a steering control assembly with embedded steering controllers. The master controller, which is in communication with each eModule and with the driver input devices, communicates with and independently controls each eModule, by-wire, via the embedded controllers to establish a desired operating mode. Modes may include a two-wheel, four-wheel, diamond, and omni-directional steering modes as well as a park mode. A bumper may enable docking with another vehicle, with shared control over the eModules of the vehicles.

  8. Structural and Functional Modularity of the Orange Carotenoid Protein: Distinct Roles for the N- and C-Terminal Domains in Cyanobacterial Photoprotection[C][W

    PubMed Central

    Leverenz, Ryan L.; Jallet, Denis; Li, Ming-De; Mathies, Richard A.; Kirilovsky, Diana; Kerfeld, Cheryl A.

    2014-01-01

    The orange carotenoid protein (OCP) serves as a sensor of light intensity and an effector of phycobilisome (PB)–associated photoprotection in cyanobacteria. Structurally, the OCP is composed of two distinct domains spanned by a single carotenoid chromophore. Functionally, in response to high light, the OCP converts from a dark-stable orange form, OCPO, to an active red form, OCPR. The C-terminal domain of the OCP has been implicated in the dynamic response to light intensity and plays a role in switching off the OCP’s photoprotective response through its interaction with the fluorescence recovery protein. The function of the N-terminal domain, which is uniquely found in cyanobacteria, is unclear. To investigate its function, we isolated the N-terminal domain in vitro using limited proteolysis of native OCP. The N-terminal domain retains the carotenoid chromophore; this red carotenoid protein (RCP) has constitutive PB fluorescence quenching activity comparable in magnitude to that of active, full-length OCPR. A comparison of the spectroscopic properties of the RCP with OCPR indicates that critical protein–chromophore interactions within the C-terminal domain are weakened in the OCPR form. These results suggest that the C-terminal domain dynamically regulates the photoprotective activity of an otherwise constitutively active carotenoid binding N-terminal domain. PMID:24399299

  9. Quantum modular forms, mock modular forms, and partial theta functions

    NASA Astrophysics Data System (ADS)

    Kimport, Susanna

    Defined by Zagier in 2010, quantum modular forms have been the subject of an explosion of recent research. Many of these results are aimed at discovering examples of these functions, which are defined on the rational numbers and have "nice" modularity properties. Though the subject is in its early stages, numerous results (including Zagier's original examples) show these objects naturally arising from many areas of mathematics as limits of other modular-like functions. One such family of examples is due to Folsom, Ono, and Rhoades, who connected these new objects to partial theta functions (introduced by Rogers in 1917) and mock modular forms (about which there is a rich theory, whose origins date back to Ramanujan in 1920). In this thesis, we build off of the work of Folsom, Ono, and Rhoades by providing an infinite family of quantum modular forms of arbitrary positive half-integral weight. Further, this family of quantum modular forms "glues" mock modular forms to partial theta functions and is constructed from a so-called "universal" mock theta function by extending a method of Eichler and Zagier (originally defined for holomorphic Jacobi forms) into a non-holomorphic setting. In addition to the infinite family, we explore the weight 1/2 and 3/2 functions in more depth. For both of these weights, we are able to explicitly write down the quantum modular form, as well as the corresponding "errors to modularity," which can be shown to be Mordell integrals of specific theta functions and, as a consequence, are real-analytic functions. Finally, we turn our attention to the partial theta functions associated with these low weight examples. Berndt and Kim provide asymptotic expansions for a certain class of partial theta functions as q approaches 1 radially within the unit disk. Here, we extend this work to not only obtain asymptotic expansions for this class of functions as q approaches any root of unity, but also for a certain class of derivatives of these functions

  10. Spacecraft Modularity for Serviceable Satellites

    NASA Technical Reports Server (NTRS)

    Rossetti, Dino; Keer, Beth; Panek, John; Ritter, Bob; Reed, Benjamin; Cepollina, Frank

    2015-01-01

    Spacecraft modularity has been a topic of interest at NASA since the 1970s, when the Multi-­-Mission Modular Spacecraft (MMS) was developed at the Goddard Space Flight Center. Since then, modular concepts have been employed for a variety of spacecraft and, as in the case of the Hubble Space Telescope (HST) and the International Space Station (ISS), have been critical to the success of on-­- orbit servicing. Modularity is even more important for future robotic servicing. Robotic satellite servicing technologies under development by NASA can extend mission life and reduce lifecycle cost and risk. These are optimized when the target spacecraft is designed for servicing, including advanced modularity. This paper will explore how spacecraft design, as demonstrated by the Reconfigurable Operational spacecraft for Science and Exploration (ROSE) spacecraft architecture, and servicing technologies can be developed in parallel to fully take advantage of the promise of both.

  11. Spacecraft Modularity for Serviceable Satellites

    NASA Technical Reports Server (NTRS)

    Reed, Benjamin B.; Rossetti, Dino; Keer, Beth; Panek, John; Cepollina, Frank; Ritter, Robert

    2015-01-01

    Spacecraft modularity has been a topic of interest at NASA since the 1970s, when the Multi-Mission Modular Spacecraft (MMS) was developed at the Goddard Space Flight Center. Since then, modular concepts have been employed for a variety of spacecraft and, as in the case of the Hubble Space Telescope (HST) and the International Space Station (ISS), have been critical to the success of on-orbit servicing. Modularity is even more important for future robotic servicing. Robotic satellite servicing technologies under development by NASA can extend mission life and reduce life-cycle cost and risk. These are optimized when the target spacecraft is designed for servicing, including advanced modularity. This paper will explore how spacecraft design, as demonstrated by the Reconfigurable Operational spacecraft for Science and Exploration (ROSE) spacecraft architecture, and servicing technologies can be developed in parallel to fully take advantage of the promise of both.

  12. The Emergence of Modularity in Biological Systems

    PubMed Central

    Lorenz, Dirk M.; Jeng, Alice; Deem, Michael W.

    2015-01-01

    In this review, we discuss modularity and hierarchy in biological systems. We review examples from protein structure, genetics, and biological networks of modular partitioning of the geometry of biological space. We review theories to explain modular organization of biology, with a focus on explaining how biology may spontaneously organize to a structured form. That is, we seek to explain how biology nucleated from among the many possibilities in chemistry. The emergence of modular organization of biological structure will be described as a symmetry-breaking phase transition, with modularity as the order parameter. Experimental support for this description will be reviewed. Examples will be presented from pathogen structure, metabolic networks, gene networks, and protein-protein interaction networks. Additional examples will be presented from ecological food networks, developmental pathways, physiology, and social networks. There once were two watchmakers, named Hora and Tempus, who manufactured very fine watches. Both of them were highly regarded, and the phones in their workshops rang frequently — new customers were constantly calling them. However, Hora prospered, while Tempus became poorer and poorer and finally lost his shop. What was the reason? The watches the men made consisted of about 1,000 parts each. Tempus had so constructed his that if he had one partly assembled and had to put it down — to answer the phone say— it immediately fell to pieces and had to be reassembled from the elements. The better the customers liked his watches, the more they phoned him, the more difficult it became for him to find enough uninterrupted time to finish a watch. The watches that Hora made were no less complex than those of Tempus. But he had designed them so that he could put together subassemblies of about ten elements each. Ten of these subassemblies, again, could be put together into a larger subassembly; and a system of ten of the latter sub

  13. The Caenorhabditis elegans gene unc-89, required fpr muscle M-line assembly, encodes a giant modular protein composed of Ig and signal transduction domains

    PubMed Central

    1996-01-01

    Mutations in the Caenorhabditis elegans gene unc-89 result in nematodes having disorganized muscle structure in which thick filaments are not organized into A-bands, and there are no M-lines. Beginning with a partial cDNA from the C. elegans sequencing project, we have cloned and sequenced the unc-89 gene. An unc-89 allele, st515, was found to contain an 84-bp deletion and a 10-bp duplication, resulting in an in- frame stop codon within predicted unc-89 coding sequence. Analysis of the complete coding sequence for unc-89 predicts a novel 6,632 amino acid polypeptide consisting of sequence motifs which have been implicated in protein-protein interactions. UNC-89 begins with 67 residues of unique sequences, SH3, dbl/CDC24, and PH domains, 7 immunoglobulins (Ig) domains, a putative KSP-containing multiphosphorylation domain, and ends with 46 Ig domains. A polyclonal antiserum raised to a portion of unc-89 encoded sequence reacts to a twitchin-sized polypeptide from wild type, but truncated polypeptides from st515 and from the amber allele e2338. By immunofluorescent microscopy, this antiserum localizes to the middle of A-bands, consistent with UNC-89 being a structural component of the M-line. Previous studies indicate that myofilament lattice assembly begins with positional cues laid down in the basement membrane and muscle cell membrane. We propose that the intracellular protein UNC-89 responds to these signals, localizes, and then participates in assembling an M-line. PMID:8603916

  14. Modular Flooring System

    NASA Technical Reports Server (NTRS)

    Thate, Robert

    2012-01-01

    The modular flooring system (MFS) was developed to provide a portable, modular, durable carpeting solution for NASA fs Robotics Alliance Project fs (RAP) outreach efforts. It was also designed to improve and replace a modular flooring system that was too heavy for safe use and transportation. The MFS was developed for use as the flooring for various robotics competitions that RAP utilizes to meet its mission goals. One of these competitions, the FIRST Robotics Competition (FRC), currently uses two massive rolls of broadloom carpet for the foundation of the arena in which the robots are contained during the competition. The area of the arena is approximately 30 by 72 ft (approximately 9 by 22 m). This carpet is very cumbersome and requires large-capacity vehicles, and handling equipment and personnel to transport and deploy. The broadloom carpet sustains severe abuse from the robots during a regular three-day competition, and as a result, the carpet is not used again for competition. Similarly, broadloom carpets used for trade shows at convention centers around the world are typically discarded after only one use. This innovation provides a green solution to this wasteful practice. Each of the flooring modules in the previous system weighed 44 lb (.20 kg). The improvements in the overall design of the system reduce the weight of each module by approximately 22 lb (.10 kg) (50 %), and utilize an improved "module-to-module" connection method that is superior to the previous system. The MFS comprises 4-by-4-ft (.1.2-by- 1.2-m) carpet module assemblies that utilize commercially available carpet tiles that are bonded to a lightweight substrate. The substrate surface opposite from the carpeted surface has a module-to-module connecting interface that allows for the modules to be connected, one to the other, as the modules are constructed. This connection is hidden underneath the modules, creating a smooth, co-planar flooring surface. The modules are stacked and strapped

  15. The modular power subsystem for the multimission modular spacecraft

    NASA Technical Reports Server (NTRS)

    Harris, D. W.

    1978-01-01

    The block diagram, subsystems, and components of the modular power subsystem for the multimission modular spacecraft (MMS) are described. The basic design studies were guided by considerations of cost, efficiency, simplicity, and flexibility to serve a variety of missions. Components discussed are the power regulator unit, the power control unit, the signal conditioning assembly, bus protection assembly, and the 20 Ah and 50 Ah batteries. The plan for the modular power subsystem protoflight module tests is shown. The testing has four phases: (1) component level tests, (2) subsystem integration and initial performance test, (3) subsystem protoflight environmental tests, and (4) subsystem final performance tests, qualification/acceptance review and delivery.

  16. Modular electronics packaging system

    NASA Technical Reports Server (NTRS)

    Hunter, Don J. (Inventor)

    2001-01-01

    A modular electronics packaging system includes multiple packaging slices that are mounted horizontally to a base structure. The slices interlock to provide added structural support. Each packaging slice includes a rigid and thermally conductive housing having four side walls that together form a cavity to house an electronic circuit. The chamber is enclosed on one end by an end wall, or web, that isolates the electronic circuit from a circuit in an adjacent packaging slice. The web also provides a thermal path between the electronic circuit and the base structure. Each slice also includes a mounting bracket that connects the packaging slice to the base structure. Four guide pins protrude from the slice into four corresponding receptacles in an adjacent slice. A locking element, such as a set screw, protrudes into each receptacle and interlocks with the corresponding guide pin. A conduit is formed in the slice to allow electrical connection to the electronic circuit.

  17. Modular error embedding

    DOEpatents

    Sandford, II, Maxwell T.; Handel, Theodore G.; Ettinger, J. Mark

    1999-01-01

    A method of embedding auxiliary information into the digital representation of host data containing noise in the low-order bits. The method applies to digital data representing analog signals, for example digital images. The method reduces the error introduced by other methods that replace the low-order bits with auxiliary information. By a substantially reverse process, the embedded auxiliary data can be retrieved easily by an authorized user through use of a digital key. The modular error embedding method includes a process to permute the order in which the host data values are processed. The method doubles the amount of auxiliary information that can be added to host data values, in comparison with bit-replacement methods for high bit-rate coding. The invention preserves human perception of the meaning and content of the host data, permitting the addition of auxiliary data in the amount of 50% or greater of the original host data.

  18. Modular Optical PDV System

    SciTech Connect

    Araceli Rutkowski, David Esquibel

    2008-12-11

    A modular optical photon Doppler velocimetry (PDV) detector system has been developed by using readily available optical components with a 20-GHz Miteq optical detector into eight channels of single-wide modules integrated into a 3U rack unit (1U = 1.75 inches) with a common power supply. Optical fibers were precisely trimmed, welded, and timed within each unit. This system has been used to collect dynamic velocity data on various physics experiments. An optical power meter displays the laser input power to the module and optical power at the detector. An adjustable micro-electromechanical system (MEMS) optical attenuator is used to adjust the amount of unshifted light entering the detector. Front panel LEDs show the presence of power to the module. A fully loaded chassis with eight channels consumes 45 watts of power. Each chassis requires 1U spacing above and below for heat management. Modules can be easily replaced.

  19. Modular arctic structures system

    SciTech Connect

    Reusswig, G. H.

    1984-12-04

    A modular and floatable offshore exploration and production platform system for use in shallow arctic waters is disclosed. A concrete base member is floated to the exploration or production site, and ballated into a predredged cavity. The cavity and base are sized to provide a stable horizontal base 30 feet below the mean water/ice plane. An exploration or production platform having a massive steel base is floated to the site and ballasted into position on the base. Together, the platform, base and ballast provide a massive gravity structure that is capable of resisting large ice and wave forces that impinge on the structure. The steel platform has a sloping hourglass profile to deflect horizontal ice loads vertically, and convert the horizontal load to a vertical tensile stress, which assists in breaking the ice as it advances toward the structure.

  20. Modular small hydro configuration

    NASA Astrophysics Data System (ADS)

    1981-09-01

    Smaller sites (those under 750 kilowatts) which previously were not attractive to develop using equipment intended for application at larger scale sites, were the focal point in the conception of a system which utilizes standard industrial components which are generally available within short procurement times. Such components were integrated into a development scheme for sites having 20 feet to 150 feet of head. The modular small hydro configuration maximizes the use of available components and minimizes modification of existing civil works. A key aspect of the development concept is the use of a vertical turbine multistage pump, used in the reverse mode as a hydraulic turbine. The configuration allows for automated operation and control of the hydroelectric facilities with sufficient flexibility for inclusion of potential hydroelectric sites into dispersed storage and generation (DSG) utility grid systems.

  1. Modular weapon control unit

    SciTech Connect

    Boccabella, M.F.; McGovney, G.N.

    1997-01-01

    The goal of the Modular Weapon Control Unit (MWCU) program was to design and develop a reconfigurable weapon controller (programmer/sequencer) that can be adapted to different weapon systems based on the particular requirements for that system. Programmers from previous systems are conceptually the same and perform similar tasks. Because of this commonality and the amount of re-engineering necessary with the advent of every new design, the idea of a modular, adaptable system has emerged. Also, the controller can be used in more than one application for a specific weapon system. Functionality has been divided into a Processor Module (PM) and an Input/Output Module (IOM). The PM will handle all operations that require calculations, memory, and timing. The IOM will handle interfaces to the rest of the system, input level shifting, output drive capability, and detection of interrupt conditions. Configuration flexibility is achieved in two ways. First, the operation of the PM is determined by a surface mount Read-Only Memory (ROM). Other surface-mount components can be added or neglected as necessary for functionality. Second, IOMs consist of configurable input buffers, configurable output drivers, and configurable interrupt generation. Further, these modules can be added singly or in groups to a Processor Module to achieve the required I/O configuration. The culmination of this LDRD was the building of both Processor Module and Input/Output Module. The MWCU was chosen as a test system to evaluate Low-Temperature Co-fired Ceramic (LTCC) technology, desirable for high component density and good thermal characteristics.

  2. Single-step Fabrication of Patterned Gold Film Array by an Engineered Multi-functional Peptide

    PubMed Central

    Hnilova, Marketa; Khatayevich, Dmitriy; Carlson, Alisa; Oren, Ersin Emre; Gresswell, Carolyn; Zheng, Sam; Ohuchi, Fumio; Sarikaya, Mehmet; Tamerler, Candan

    2013-01-01

    This study constitutes a demonstration of the biological route to controlled nano-fabrication via modular multi-functional inorganic-binding peptides. Specifically, we use gold- and silica-binding peptide sequences, fused into a single molecule via a structural peptide spacer, to assemble pre-synthesized gold nanoparticles on silica surface, as well as to synthesize nanometallic particles in situ on the peptide-patterned regions. The resulting film-like gold nanoparticle arrays with controlled spatial organization are characterized by various microscopy and spectroscopy techniques. The described bio-enabled, single-step synthetic process offers many advantages over conventional approaches for surface modifications, self-assembly and device fabrication due to the peptides’ modularity, inherent biocompatibility, material specificity and catalytic activity in aqueous environments. Our results showcase the potential of artificially-derived peptides to play a key role in simplifying the assembly and synthesis of multi-material nano-systems in environmentally benign processes. PMID:21962430

  3. Locally rare species influence grassland ecosystem multifunctionality.

    PubMed

    Soliveres, Santiago; Manning, Peter; Prati, Daniel; Gossner, Martin M; Alt, Fabian; Arndt, Hartmut; Baumgartner, Vanessa; Binkenstein, Julia; Birkhofer, Klaus; Blaser, Stefan; Blüthgen, Nico; Boch, Steffen; Böhm, Stefan; Börschig, Carmen; Buscot, Francois; Diekötter, Tim; Heinze, Johannes; Hölzel, Norbert; Jung, Kirsten; Klaus, Valentin H; Klein, Alexandra-Maria; Kleinebecker, Till; Klemmer, Sandra; Krauss, Jochen; Lange, Markus; Morris, E Kathryn; Müller, Jörg; Oelmann, Yvonne; Overmann, Jörg; Pašalić, Esther; Renner, Swen C; Rillig, Matthias C; Schaefer, H Martin; Schloter, Michael; Schmitt, Barbara; Schöning, Ingo; Schrumpf, Marion; Sikorski, Johannes; Socher, Stephanie A; Solly, Emily F; Sonnemann, Ilja; Sorkau, Elisabeth; Steckel, Juliane; Steffan-Dewenter, Ingolf; Stempfhuber, Barbara; Tschapka, Marco; Türke, Manfred; Venter, Paul; Weiner, Christiane N; Weisser, Wolfgang W; Werner, Michael; Westphal, Catrin; Wilcke, Wolfgang; Wolters, Volkmar; Wubet, Tesfaye; Wurst, Susanne; Fischer, Markus; Allan, Eric

    2016-05-19

    Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities. PMID:27114572

  4. The tight junction: a multifunctional complex.

    PubMed

    Schneeberger, Eveline E; Lynch, Robert D

    2004-06-01

    Multicellular organisms are separated from the external environment by a layer of epithelial cells whose integrity is maintained by intercellular junctional complexes composed of tight junctions, adherens junctions, and desmosomes, whereas gap junctions provide for intercellular communication. The aim of this review is to present an updated overview of recent developments in the area of tight junction biology. In a relatively short time, our knowledge of the tight junction has evolved from a relatively simple view of it being a permeability barrier in the paracellular space and a fence in the plane of the plasma membrane to one of it acting as a multicomponent, multifunctional complex that is involved in regulating numerous and diverse cell functions. A group of integral membrane proteins-occludin, claudins, and junction adhesion molecules-interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity. PMID:15151915

  5. Some new modular equations and their applications

    NASA Astrophysics Data System (ADS)

    Yi, Jinhee; Sim, Hyo Seob

    2006-07-01

    Ramanujan derived 23 beautiful eta-function identities, which are certain types of modular equations. We found more than 70 of certain types of modular equations by using Garvan's Maple q-series package. In this paper, we prove some new modular equations which we found by employing the theory of modular form and we give some applications for them.

  6. Bi- or multifunctional peptide drugs

    PubMed Central

    Schiller, Peter W.

    2009-01-01

    Strategies for the design of bi- or multifunctional drugs are reviewed. A distinction is made between bifunctional drugs interacting in a monovalent fashion with two targets and ligands containing two distinct pharmacophores binding in a bivalent mode to the two binding sites in a receptor heterodimer. Arguments are presented to indicate that some of the so-called “bivalent” ligands reported in the literature are unlikely to simultaneously interact with two binding sites. Aspects related to the development of bi- or multifunctional drugs are illustrated with examples from the field of opioid analgesics. The drug-like properties of the tetrapeptide Dmt1[DALDA] with triple action as a μ opioid agonist, norepinephrine uptake inhibitor and releaser of endogenous opioid peptides to produce potent spinal analgesia are reviewed. Rationales for the development of opioid peptides with mixed agonist/antagonist profiles as analgesics with reduced side effects are presented. Progress in the development of mixed μ opioid agonist/δ opioid antagonists with low propensity to produce tolerance and physical dependence is reviewed. Efforts to develop bifunctional peptides containing a μ opioid agonist and a cholecystokinin antagonist or an NK1 receptor antagonist as analgesics expected to produce less tolerance and dependence are also reviewed. A strategy to improve the drug-like properties of bifunctional opioid peptide analgesics is presented. PMID:19285088

  7. Multifunction sensor for target recognition

    NASA Astrophysics Data System (ADS)

    James, William M.; Lindberg, Perry C.

    1993-09-01

    The U.S. Army has a critical need for the capability provided by a multifunction sensor. This is (in effect) a smart sensor system that can adapt to environmental conditions and adjust its mode of operation to effectively counter any threat it meets. It will have an intelligent signal processor which has all of the system's sensor signals to choose from. The processor chooses the appropriate signal information to rapidly detect, acquire, track, and automatically identify all targets in the vicinity of the sensor under a wide variety of battlefield scenarios and environmental conditions. The multiphenomenology signal information provides the flexibility to overcome the adverse effects of clutter, countermeasures (both active and passive), illumination, obscurants, target orientation, and weather. It should be noted, however, that the types of sensory information required is dependent on the mission and the operating environment. For instance, a strategic defense sensor operating in space can use (and will need) different types of sensor data than the multifunction sensor employed on an attack helicopter. In fact, the sensor configuration on a helicopter operating in Saudi Arabia may be quite different from one that is deployed to Vietnam. For the purpose of this paper we generalize about the technologies desired for an adaptable, `smart' sensor system. We do not specify a particular mission nor define a specific threat. However, in any case, we can assume the need to fuse sensor signal information in an intelligent processor to provide robust performance in the battlefield environment. 12

  8. Electrospun multifunctional tissue engineering scaffolds

    NASA Astrophysics Data System (ADS)

    Wang, Chong; Wang, Min

    2014-03-01

    Tissue engineering holds great promises in providing successful treatments of human body tissue loss that current methods are unable to treat or unable to achieve satisfactory clinical outcomes. In scaffold-based tissue engineering, a highperformance scaffold underpins the success of a tissue engineering strategy and a major direction in the field is to create multifunctional tissue engineering scaffolds for enhanced biological performance and for regenerating complex body tissues. Electrospinning can produce nanofibrous scaffolds that are highly desirable for tissue engineering. The enormous interest in electrospinning and electrospun fibrous structures by the science, engineering and medical communities has led to various developments of the electrospinning technology and wide investigations of electrospun products in many industries, including biomedical engineering, over the past two decades. It is now possible to create novel, multicomponent tissue engineering scaffolds with multiple functions. This article provides a concise review of recent advances in the R & D of electrospun multifunctional tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of electrospun multicomponent scaffolds with multiple functions.

  9. Multifunctional ORMOSIL and PAA nanoparticles

    NASA Astrophysics Data System (ADS)

    Gupta, Anurag; Rao, K. V. R.; Pera, Paula; Wang, Shouyan J.; Missert, Joseph R.; Ohulchanskyy, Tymish; Roy, Indrajit; Morgan, Janet; Prasad, Paras N.; Kopelman, Raoul; Pandey, Ravindra K.

    2009-06-01

    Various problems arising during molecular imaging of different fluoroprobes and metabolites used in PDT can be circumvented by focusing on multifunctional therapy agents. Thus an effective photo sensitizer coupled with other useful roles to play in PDT treatment make nanoparticles as a good vehicle for different delivery assuming multifunctional roles not only in PDT but also as therapeutic agents for targeted delivery. A new approach is the involving use of 100 nm NPs as photo sensitizers and/or imaging agents. In our Lab., we employ two such NPs and are ORMOSIL (organically Modified Silica) and PAA (Polyacrylamide) which are found to be biologically very safe without disturbing the therapeutic value. The size of the nanoparticles determined by TEM and Dynamic Light Scattering are ~30 nm. These NPs are taken up in conjunction with cyanine dye at near infra red as it has been reported in literature that encapsulated NPs shows very low singlet oxygen production compared with the post-loaded NPs though the reasons are not yet clear. Therefore, we investigated the idea of post-loading or adsorbing vis-a-vis encapsulation.

  10. A Detailed Modular Analysis of Heat-Shock Protein Dynamics under Acute and Chronic Stress and Its Implication in Anxiety Disorders

    PubMed Central

    Sriram, K.; Rodriguez-Fernandez, Maria; Doyle, Francis J.

    2012-01-01

    Physiological and psychological stresses cause anxiety disorders such as depression and post-traumatic stress disorder (PTSD) and induce drastic changes at a molecular level in the brain. To counteract this stress, the heat-shock protein (HSP) network plays a vital role in restoring the homeostasis of the system. To study the stress-induced dynamics of heat-shock network, we analyzed three modules of the HSP90 network—namely trimerization reactions, phosphorylation–dephosphorylation reactions, and the conversion of HSP90 from an open to a closed conformation—and constructed a corresponding nonlinear differential equation model based on mass action kinetics laws. The kinetic parameters of the model were obtained through global optimization, and sensitivity analyses revealed that the most sensitive parameters are the kinase and phosphatase that drive the phosphorylation–dephosphorylation reactions. Bifurcation analysis carried out with the estimated kinetic parameters of the model with stress as bifurcation parameter revealed the occurrence of “mushroom”, a type of complex dynamics in which S-shaped and Z-shaped hysteretic bistable forms are present together. We mapped the molecular events responsible for generating the mushroom dynamics under stress and interpreted the occurrence of the S-shaped hysteresis to a normal level of stress, and the Z-shaped hysteresis to the HSP90 variations under acute and chronic stress in the fear conditioned system, and further, we hypothesized that this can be extended to stress-related disorders such as depression and PTSD in humans. Finally, we studied the effect of parameter variations on the mushroom dynamics to get insight about the role of phosphorylation–dephosphorylation parameters in HSP90 network in bringing about complex dynamics such as isolas, where the stable steady states in a bistable system are isolated and separated from each other and not connected by an unstable steady state. PMID:22937003

  11. Magnetic-encoded fluorescent multifunctional nanospheres for simultaneous multicomponent analysis.

    PubMed

    Song, Erqun; Han, Weiye; Li, Jingrong; Jiang, Yunfei; Cheng, Dan; Song, Yang; Zhang, Pu; Tan, Weihong

    2014-10-01

    In this study, magnetic-encoded fluorescent (CdTe/Fe3O4)@SiO2 multifunctional nanospheres were constructed by adjusting the initial concentration of Fe3O4 in a fabrication process based on reverse microemulsion. The resultant multifunctional nanospheres were characterized by transmission electron microscopy, X-ray diffraction measurements, fluorescence spectrophotometry, and vibrating sample magnetometry. They showed good fluorescence properties, gradient magnetic susceptibility (weak, moderate, and strong), and easy biofunctionalization for biomolecules, such as immunoglobulin G (IgG), protein, and antibody. Then the capture efficiency of the (CdTe/Fe3O4)@SiO2 nanospheres were investigated by using the fluorophore-labeled IgG-conjugated nanospheres as a model. Further studies demonstrated the ability of these (CdTe/Fe3O4)@SiO2 multifunctional nanospheres to accomplish sequentially magnetic separation, capture, and fluorescent detection for each corresponding antigen of CA125, AFP, and CEA with a detection limit of 20 KU/L, 10 ng/mL, and 5 ng/mL, respectively, from a mixed sample under a certain external magnetic field within a few minutes. The strategy of combining magnetic-encoding-based separation and fluorescence-based detection proposed in this study shows great potential to achieve easy, rapid, economical, and near-simultaneous multicomponent separation and analysis for a variety of targets such as drugs, biomarkers, pathogens, and so on. PMID:25197942

  12. The evolutionary origins of modularity.

    PubMed

    Clune, Jeff; Mouret, Jean-Baptiste; Lipson, Hod

    2013-03-22

    A central biological question is how natural organisms are so evolvable (capable of quickly adapting to new environments). A key driver of evolvability is the widespread modularity of biological networks--their organization as functional, sparsely connected subunits--but there is no consensus regarding why modularity itself evolved. Although most hypotheses assume indirect selection for evolvability, here we demonstrate that the ubiquitous, direct selection pressure to reduce the cost of connections between network nodes causes the emergence of modular networks. Computational evolution experiments with selection pressures to maximize network performance and minimize connection costs yield networks that are significantly more modular and more evolvable than control experiments that only select for performance. These results will catalyse research in numerous disciplines, such as neuroscience and genetics, and enhance our ability to harness evolution for engineering purposes. PMID:23363632

  13. The evolutionary origins of modularity

    PubMed Central

    Clune, Jeff; Mouret, Jean-Baptiste; Lipson, Hod

    2013-01-01

    A central biological question is how natural organisms are so evolvable (capable of quickly adapting to new environments). A key driver of evolvability is the widespread modularity of biological networks—their organization as functional, sparsely connected subunits—but there is no consensus regarding why modularity itself evolved. Although most hypotheses assume indirect selection for evolvability, here we demonstrate that the ubiquitous, direct selection pressure to reduce the cost of connections between network nodes causes the emergence of modular networks. Computational evolution experiments with selection pressures to maximize network performance and minimize connection costs yield networks that are significantly more modular and more evolvable than control experiments that only select for performance. These results will catalyse research in numerous disciplines, such as neuroscience and genetics, and enhance our ability to harness evolution for engineering purposes. PMID:23363632

  14. Modular Arithmetic in the Marketplace.

    ERIC Educational Resources Information Center

    Gallian, Joseph A.; Winters, Steven

    1988-01-01

    Several schemes use modular arithmetic to append a check digit to product identification numbers for error detection. Some schemes are discussed, including ones for money orders and library books. Then a foolproof method is presented. (MNS)

  15. The modularity of pollination networks

    PubMed Central

    Olesen, Jens M.; Bascompte, Jordi; Dupont, Yoko L.; Jordano, Pedro

    2007-01-01

    In natural communities, species and their interactions are often organized as nonrandom networks, showing distinct and repeated complex patterns. A prevalent, but poorly explored pattern is ecological modularity, with weakly interlinked subsets of species (modules), which, however, internally consist of strongly connected species. The importance of modularity has been discussed for a long time, but no consensus on its prevalence in ecological networks has yet been reached. Progress is hampered by inadequate methods and a lack of large datasets. We analyzed 51 pollination networks including almost 10,000 species and 20,000 links and tested for modularity by using a recently developed simulated annealing algorithm. All networks with >150 plant and pollinator species were modular, whereas networks with <50 species were never modular. Both module number and size increased with species number. Each module includes one or a few species groups with convergent trait sets that may be considered as coevolutionary units. Species played different roles with respect to modularity. However, only 15% of all species were structurally important to their network. They were either hubs (i.e., highly linked species within their own module), connectors linking different modules, or both. If these key species go extinct, modules and networks may break apart and initiate cascades of extinction. Thus, species serving as hubs and connectors should receive high conservation priorities. PMID:18056808

  16. Spacecraft Modularity for Serviceable Satellites

    NASA Technical Reports Server (NTRS)

    Rossetti, Dino; Keer, Beth; Panek, John; Reed, Benjamin; Cepollina, Frank; Ritter, Robert

    2015-01-01

    Satellite servicing has been a proven capability of NASA since the first servicing missions in the 1980s with astronauts on the space shuttle. This capability enabled the on-orbit assembly of the International Space Station (ISS) and saved the Hubble Space Telescope (HST) mission following the discovery of the flawed primary mirror. The effectiveness and scope of servicing opportunities, especially using robotic servicers, is a function of how cooperative a spacecraft is. In this paper, modularity will be presented as a critical design aspect for a spacecraft that is cooperative from a servicing perspective. Different features of modularity are discussed using examples from HST and the Multimission Modular Spacecraft (MMS) program from the 1980s and 1990s. The benefits of modularity will be presented including those directly related to servicing and those outside of servicing including reduced costs and increased flexibility. The new Reconfigurable Operational spacecraft for Science and Exploration (ROSE) concept is introduced as an affordable implementation of modularity that provides cost savings and flexibility. Key aspects of the ROSE architecture are discussed such as the module design and the distributed avionics architecture. The ROSE concept builds on the experience from MMS and due to its modularity, would be highly suitable as a future client for on-orbit servicing.

  17. Modular Approach to Spintronics

    PubMed Central

    Camsari, Kerem Yunus; Ganguly, Samiran; Datta, Supriyo

    2015-01-01

    There has been enormous progress in the last two decades, effectively combining spintronics and magnetics into a powerful force that is shaping the field of memory devices. New materials and phenomena continue to be discovered at an impressive rate, providing an ever-increasing set of building blocks that could be exploited in designing transistor-like functional devices of the future. The objective of this paper is to provide a quantitative foundation for this building block approach, so that new discoveries can be integrated into functional device concepts, quickly analyzed and critically evaluated. Through careful benchmarking against available theory and experiment we establish a set of elemental modules representing diverse materials and phenomena. These elemental modules can be integrated seamlessly to model composite devices involving both spintronic and nanomagnetic phenomena. We envision the library of modules to evolve both by incorporating new modules and by improving existing modules as the field progresses. The primary contribution of this paper is to establish the ground rules or protocols for a modular approach that can build a lasting bridge between materials scientists and circuit designers in the field of spintronics and nanomagnetics. PMID:26066079

  18. Modular Isotopic Thermoelectric Generator

    SciTech Connect

    Schock, Alfred

    1981-04-03

    Advanced RTG concepts utilizing improved thermoelectric materials and converter concepts are under study at Fairchild for DOE. The design described here is based on DOE's newly developed radioisotope heat source, and on an improved silicon-germanium material and a multicouple converter module under development at Syncal. Fairchild's assignment was to combine the above into an attractive power system for use in space, and to assess the specific power and other attributes of that design. The resultant design is highly modular, consisting of standard RTG slices, each producing ~24 watts at the desired output voltage of 28 volt. Thus, the design could be adapted to various space missions over a wide range of power levels, with little or no redesign. Each RTG slice consists of a 250-watt heat source module, eight multicouple thermoelectric modules, and standard sections of insulator, housing, radiator fins, and electrical circuit. The design makes it possible to check each thermoelectric module for electrical performance, thermal contact, leaktightness, and performance stability, after the generator is fully assembled; and to replace any deficient modules without disassembling the generator or perturbing the others. The RTG end sections provide the spring-loaded supports required to hold the free-standing heat source stack together during launch vibration. Details analysis indicates that the design offers a substantial improvement in specific power over the present generator of RTGs, using the same heat source modules. There are three copies in the file.

  19. A Biomimetic Modular Polymer with Tough and Adaptive Properties

    PubMed Central

    Kushner, Aaron M.; Vossler, John; Williams, Gregory A.; Guan, Zhibin

    2009-01-01

    Natural materials employ many elegant strategies to achieve mechanical properties required for survival under varying environmental conditions. Thus these remarkable biopolymers and nanocomposites often not only have a combination of mechanical properties such as high modulus, toughness, and elasticity, but also exhibit adaptive and stimuli-responsive properties. Inspired by skeletal muscle protein titin, we have synthesized a biomimetic modular polymer that not only closely mimics the modular multi-domain structure of titin, but also manifests an exciting combination of mechanical properties, as well as adaptive properties such as self-healing and temperature-responsive shape-memory properties. PMID:19505144

  20. Multifunction display system, volume 1

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The design and construction of a multifunction display man/machine interface for use with a 4 pi IBM-360 System are described. The system is capable of displaying superimposed volatile alphanumeric and graphical data on a 512 x 512 element plasma panel, and holographically stored multicolor archival information. The volatile data may be entered from a keyboard or by means of an I/O interface to the 360 system. A 2-page memory local to the display is provided for storing the entered data. The archival data is stored as a phase hologram on a vinyl tape strip. This data is accessible by means of a rapid transport system which responds to inputs provided by the I/O channel on the keyboard. As many as 500 frames may be stored on a tape strip for access in under 6 seconds.

  1. Multifunctionalities driven by ferroic domains

    SciTech Connect

    Yang, J. C.; Huang, Y. L.; Chu, Y. H.; He, Q.

    2014-08-14

    Considerable attention has been paid to ferroic systems in pursuit of advanced applications in past decades. Most recently, the emergence and development of multiferroics, which exhibit the coexistence of different ferroic natures, has offered a new route to create functionalities in the system. In this manuscript, we step from domain engineering to explore a roadmap for discovering intriguing phenomena and multifunctionalities driven by periodic domain patters. As-grown periodic domains, offering exotic order parameters, periodic local perturbations and the capability of tailoring local spin, charge, orbital and lattice degrees of freedom, are introduced as modeling templates for fundamental studies and novel applications. We discuss related significant findings on ferroic domain, nanoscopic domain walls, and conjunct heterostructures based on the well-organized domain patterns, and end with future prospects and challenges in the field.

  2. Synthetic approaches to multifunctional indenes

    PubMed Central

    López-Pérez, Sara; Dinarès, Immaculada

    2011-01-01

    Summary The synthesis of multifunctional indenes with at least two different functional groups has not yet been extensively explored. Among the plausible synthetic routes to 3,5-disubstituted indenes bearing two different functional groups, such as the [3-(aminoethyl)inden-5-yl)]amines, a reasonable pathway involves the (5-nitro-3-indenyl)acetamides as key intermediates. Although several multistep synthetic approaches can be applied to obtain these advanced intermediates, we describe herein their preparation by an aldol-type reaction between 5-nitroindan-1-ones and the lithium salt of N,N-disubstituted acetamides, followed immediately by dehydration with acid. This classical condensation process, which is neither simple nor trivial despite its apparent directness, permits an efficient entry to a variety of indene-based molecular modules, which could be adapted to a range of functionalized indanones. PMID:22238553

  3. Multifunctional aliphatic polyester nanofibers for tissue engineering.

    PubMed

    Zhan, Jianan; Singh, Anirudha; Zhang, Zhe; Huang, Ling; Elisseeff, Jennifer H

    2012-01-01

    Electrospun fibers based on aliphatic polyesters, such as poly(ε-caprolactone) (PCL), have been widely used in regenerative medicine and drug delivery applications due to their biocompatibility, low cost and ease of fabrication. However, these aliphatic polyester fibers are hydrophobic in nature, resulting in poor wettability, and they lack functional groups for decorating the scaffold with chemical and biological cues. Current strategies employed to overcome these challenges include coating and blending the fibers with bioactive components or chemically modifying the fibers with plasma treatment and reactants. In the present study, we report on designing multifunctional electrospun nanofibers based on the inclusion complex of PCL-α-cyclodextrin (PCL-α-CD), which provides both structural support and multiple functionalities for further conjugation of bioactive components. This strategy is independent of any chemical modification of the PCL main chain, and electrospinning of PCL-α-CD is as easy as electrospinning PCL. Here, we describe synthesis of the PCL-α-CD electrospun nanofibers, elucidate composition and structure, and demonstrate the utility of functional groups on the fibers by conjugating a fluorescent small molecule and a polymeric-nanobead to the nanofibers. Furthermore, we demonstrate the application of PCL-α-CD nanofibers for promoting osteogenic differentiation of human adipose-derived stem cells (hADSCs), which induced a higher level of expression of osteogenic markers and enhanced production of extracellular matrix (ECM) proteins or molecules compared with control PCL fibers. PMID:23507886

  4. Multifunctional composites for energy storage

    NASA Astrophysics Data System (ADS)

    Shuvo, Mohammad Arif I.; Karim, Hasanul; Rajib, Md; Delfin, Diego; Lin, Yirong

    2014-03-01

    Electrochemical super-capacitors have become one of the most important topics in both academia and industry as novel energy storage devices because of their high power density, long life cycles, and high charge/discharge efficiency. Recently, there has been an increasing interest in the development of multifunctional structural energy storage devices such as structural super-capacitors for applications in aerospace, automobiles and portable electronics. These multifunctional structural super-capacitors provide lighter structures combining energy storage and load bearing functionalities. Due to their superior materials properties, carbon fiber composites have been widely used in structural applications for aerospace and automotive industries. Besides, carbon fiber has good electrical conductivity which will provide lower equivalent series resistance; therefore, it can be an excellent candidate for structural energy storage applications. Hence, this paper is focused on performing a pilot study for using nanowire/carbon fiber hybrids as building materials for structural energy storage materials; aiming at enhancing the charge/discharge rate and energy density. This hybrid material combines the high specific surface area of carbon fiber and pseudo-capacitive effect of metal oxide nanowires which were grown hydrothermally in an aligned fashion on carbon fibers. The aligned nanowire array could provide a higher specific surface area that leads to high electrode-electrolyte contact area and fast ion diffusion rates. Scanning Electron Microscopy (SEM) and XRay Diffraction (XRD) measurements were used for the initial characterization of this nanowire/carbon fiber hybrid material system. Electrochemical testing has been performed using a potentio-galvanostat. The results show that gold sputtered nanowire hybrid carbon fiber provides 65.9% better performance than bare carbon fiber cloth as super-capacitor.

  5. DynaMod: dynamic functional modularity analysis

    PubMed Central

    Sun, Choong-Hyun; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

    2010-01-01

    A comprehensive analysis of enriched functional categories in differentially expressed genes is important to extract the underlying biological processes of genome-wide expression profiles. Moreover, identification of the network of significant functional modules in these dynamic processes is an interesting challenge. This study introduces DynaMod, a web-based application that identifies significant functional modules reflecting the change of modularity and differential expressions that are correlated with gene expression profiles under different conditions. DynaMod allows the inspection of a wide variety of functional modules such as the biological pathways, transcriptional factor–target gene groups, microRNA–target gene groups, protein complexes and hub networks involved in protein interactome. The statistical significance of dynamic functional modularity is scored based on Z-statistics from the average of mutual information (MI) changes of involved gene pairs under different conditions. Significantly correlated gene pairs among the functional modules are used to generate a correlated network of functional categories. In addition to these main goals, this scoring strategy supports better performance to detect significant genes in microarray analyses, as the scores of correlated genes show the superior characteristics of the significance analysis compared with those of individual genes. DynaMod also offers cross-comparison between different analysis outputs. DynaMod is freely accessible at http://piech.kaist.ac.kr/dynamod. PMID:20460468

  6. Modular Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

    2016-01-01

    High-efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRGs) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high-specific-power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTGs). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and the Department of Energy (DOE) called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered, which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provided about 50 to 450 W of direct current (DC) to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator, which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific

  7. Modular Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

    2015-01-01

    High efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRG) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high specific power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTG). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and DOE called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provide about 50 to 450 watts DC to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific power may be slightly lower than the ASRG and

  8. Mussel-inspired surface chemistry for multifunctional coatings.

    PubMed

    Lee, Haeshin; Dellatore, Shara M; Miller, William M; Messersmith, Phillip B

    2007-10-19

    We report a method to form multifunctional polymer coatings through simple dip-coating of objects in an aqueous solution of dopamine. Inspired by the composition of adhesive proteins in mussels, we used dopamine self-polymerization to form thin, surface-adherent polydopamine films onto a wide range of inorganic and organic materials, including noble metals, oxides, polymers, semiconductors, and ceramics. Secondary reactions can be used to create a variety of ad-layers, including self-assembled monolayers through deposition of long-chain molecular building blocks, metal films by electroless metallization, and bioinert and bioactive surfaces via grafting of macromolecules. PMID:17947576

  9. Advanced Multifunctional MMOD Shield: Radiation Shielding Assessment

    NASA Technical Reports Server (NTRS)

    Rojdev, Kristina; Christiansen, Eric

    2013-01-01

    Deep space missions must contend with a harsh radiation environment Impacts to crew and electronics. Need to invest in multifunctionality for spacecraft optimization. MMOD shield. Goals: Increase radiation mitigation potential. Retain overall MMOD shielding performance.

  10. Microbial diversity drives multifunctionality in terrestrial ecosystems

    PubMed Central

    Delgado-Baquerizo, Manuel; Maestre, Fernando T.; Reich, Peter B.; Jeffries, Thomas C.; Gaitan, Juan J.; Encinar, Daniel; Berdugo, Miguel; Campbell, Colin D.; Singh, Brajesh K.

    2016-01-01

    Despite the importance of microbial communities for ecosystem services and human welfare, the relationship between microbial diversity and multiple ecosystem functions and services (that is, multifunctionality) at the global scale has yet to be evaluated. Here we use two independent, large-scale databases with contrasting geographic coverage (from 78 global drylands and from 179 locations across Scotland, respectively), and report that soil microbial diversity positively relates to multifunctionality in terrestrial ecosystems. The direct positive effects of microbial diversity were maintained even when accounting simultaneously for multiple multifunctionality drivers (climate, soil abiotic factors and spatial predictors). Our findings provide empirical evidence that any loss in microbial diversity will likely reduce multifunctionality, negatively impacting the provision of services such as climate regulation, soil fertility and food and fibre production by terrestrial ecosystems. PMID:26817514

  11. Microbial diversity drives multifunctionality in terrestrial ecosystems.

    PubMed

    Delgado-Baquerizo, Manuel; Maestre, Fernando T; Reich, Peter B; Jeffries, Thomas C; Gaitan, Juan J; Encinar, Daniel; Berdugo, Miguel; Campbell, Colin D; Singh, Brajesh K

    2016-01-01

    Despite the importance of microbial communities for ecosystem services and human welfare, the relationship between microbial diversity and multiple ecosystem functions and services (that is, multifunctionality) at the global scale has yet to be evaluated. Here we use two independent, large-scale databases with contrasting geographic coverage (from 78 global drylands and from 179 locations across Scotland, respectively), and report that soil microbial diversity positively relates to multifunctionality in terrestrial ecosystems. The direct positive effects of microbial diversity were maintained even when accounting simultaneously for multiple multifunctionality drivers (climate, soil abiotic factors and spatial predictors). Our findings provide empirical evidence that any loss in microbial diversity will likely reduce multifunctionality, negatively impacting the provision of services such as climate regulation, soil fertility and food and fibre production by terrestrial ecosystems. PMID:26817514

  12. Multifunctional imaging probe based on gadofulleride nanoplatform

    NASA Astrophysics Data System (ADS)

    Zheng, Jun-Peng; Liu, Qiao-Ling; Zhen, Ming-Ming; Jiang, Feng; Shu, Chun-Ying; Jin, Chan; Yang, Yongji; Alhadlaq, Hisham A.; Wang, Chun-Ru

    2012-05-01

    A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity.A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity. Electronic supplementary information (ESI) available: Materials, instruments and methods, synthesis details, XPS characterization for estimation of average molecular formula, evaluation of conjugated FA and FITC ratio, zeta potential and fluorescent images. See DOI: 10.1039/c2nr30836c

  13. Studies in Multifunctional Drug Development: Preparation and Evaluation of 11beta-Substituted Estradiol-Drug Conjugates, Cell Membrane Targeting Imaging Agents, and Target Multifunctional Nanoparticles

    NASA Astrophysics Data System (ADS)

    Dao, KinhLuan Lenny D.

    Cancer is the second leading cause of death after cardiovascular disease in the United State. Despite extensive research in development of antitumor drugs, most of these therapeutic entities often possess nonspecific toxicity, thus they can only be used to treat tumors in higher doses or more frequently. Because of the cytotoxicity and severe side effects, the drug therapeutic window normally is limited. Beside the toxicity issue, antitumor drug are also not selectively taken up by tumor cells, thus the necessitating concentrations that would eradicate the tumor can often not be used. In addition, tumor cells tend to develop resistance against the anticancer drugs after prolonged treatment. Therefore, alleviating the systemic cytotoxicity and side effects, improving in tumor selectivity, high potency, and therapeutic efficacy are still major obstacles in the area of anticancer drug development. A more promising approach for developing a selective agent for cancer is to conjugate a potent therapeutic drug, or an imaging agent with a targeting group, such as antibody or a high binding-specificity small molecule, that selectively recognize the overexpressed antigens or proteins on tumor cells. My research combines several approaches to describe this strategy via using different targeting molecules to different diseases, as well as different potent cytotoxic drugs for different therapies. Three studies related to the preparation and biological evaluation of new therapeutic agents, such as estradiol-drug hybrids, cell membrane targeted molecular imaging agents, and multifunctional NPs will be discussed. The preliminary results of these studies indicated that our new reagents achieved their initial objectives and can be further improved for optimized synthesis and in vivo experiments. The first study describes the method in which we employed a modular assembly approach to synthesize a novel 11beta-substituted steroidal anti-estrogen. The key intermediate was synthesized

  14. Modular electron transfer circuits for synthetic biology

    PubMed Central

    Agapakis, Christina M

    2010-01-01

    Electron transfer is central to a wide range of essential metabolic pathways, from photosynthesis to fermentation. The evolutionary diversity and conservation of proteins that transfer electrons makes these pathways a valuable platform for engineered metabolic circuits in synthetic biology. Rational engineering of electron transfer pathways containing hydrogenases has the potential to lead to industrial scale production of hydrogen as an alternative source of clean fuel and experimental assays for understanding the complex interactions of multiple electron transfer proteins in vivo. We designed and implemented a synthetic hydrogen metabolism circuit in Escherichia coli that creates an electron transfer pathway both orthogonal to and integrated within existing metabolism. The design of such modular electron transfer circuits allows for facile characterization of in vivo system parameters with applications toward further engineering for alternative energy production. PMID:21468209

  15. Does multifunctionality matter to US farmers? Farmer motivations and conceptions of multifunctionality in dairy systems.

    PubMed

    Brummel, Rachel F; Nelson, Kristen C

    2014-12-15

    The concept of multifunctionality describes and promotes the multiple non-production benefits that emerge from agricultural systems. The notion of multifunctional agriculture was conceived in a European context and largely has been used in European policy arenas to promote and protect the non-production goods emerging from European agriculture. Thus scholars and policy-makers disagree about the relevance of multifunctionality for United States agricultural policy and US farmers. In this study, we explore lived expressions of multifunctional agriculture at the farm-level to examine the salience of the multifunctionality concept in the US. In particular, we investigate rotational grazing and confinement dairy farms in the eastern United States as case studies of multifunctional and productivist agriculture. We also analyze farmer motivations for transitioning from confinement dairy to rotational grazing systems. Through interviews with a range of dairy producers in Wisconsin, Pennsylvania, and New York, we found that farmers were motivated by multiple factors--including improved cow health and profitability--to transition to rotational grazing systems to achieve greater farm-level multifunctionality. Additionally, rotational grazing farmers attributed a broader range of production and non-production benefits to their farm practice than confinement dairy farmers. Further, rotational grazing dairy farmers described a system-level notion of multifunctionality based on the interdependence of multiple benefits across scales--from the farm to the national level--emerging from grazing operations. We find that the concept of multifunctionality could be expanded in the US to address the interdependence of benefits emerging from farming practices, as well as private benefits to farmers. We contend that understanding agricultural benefits as experienced by the farmer is an important contribution to enriching the multifunctionality concept in the US context, informing agri

  16. Product modular design incorporating preventive maintenance issues

    NASA Astrophysics Data System (ADS)

    Gao, Yicong; Feng, Yixiong; Tan, Jianrong

    2016-03-01

    Traditional modular design methods lead to product maintenance problems, because the module form of a system is created according to either the function requirements or the manufacturing considerations. For solving these problems, a new modular design method is proposed with the considerations of not only the traditional function related attributes, but also the maintenance related ones. First, modularity parameters and modularity scenarios for product modularity are defined. Then the reliability and economic assessment models of product modularity strategies are formulated with the introduction of the effective working age of modules. A mathematical model used to evaluate the difference among the modules of the product so that the optimal module of the product can be established. After that, a multi-objective optimization problem based on metrics for preventive maintenance interval different degrees and preventive maintenance economics is formulated for modular optimization. Multi-objective GA is utilized to rapidly approximate the Pareto set of optimal modularity strategy trade-offs between preventive maintenance cost and preventive maintenance interval difference degree. Finally, a coordinate CNC boring machine is adopted to depict the process of product modularity. In addition, two factorial design experiments based on the modularity parameters are constructed and analyzed. These experiments investigate the impacts of these parameters on the optimal modularity strategies and the structure of module. The research proposes a new modular design method, which may help to improve the maintainability of product in modular design.

  17. Mussel-inspired dendritic polymers as universal multifunctional coatings.

    PubMed

    Wei, Qiang; Achazi, Katharina; Liebe, Hendrik; Schulz, Andrea; Noeske, Paul-Ludwig Michael; Grunwald, Ingo; Haag, Rainer

    2014-10-20

    A rapid and universal approach for multifunctional material coatings was developed based on a mussel-inspired dendritic polymer. This new kind of polymer mimics not only the functional groups of mussel foot proteins (mfps) but also their molecular weight and molecular structure. The large number of catechol and amine groups set the basis for heteromultivalent anchoring and crosslinking. The molecular weight reaches 10 kDa, which is similar to the most adhesive mussel foot protein mfp-5. Also, the dendritic structure exposes its functional groups on the surface like the folded proteins. As a result, a very stable coating can be prepared on virtually any type of material surface within 10 min by a simple dip-coating method, which is as fast as the formation of mussel byssal threads in nature. PMID:25200129

  18. From "Weak" to "Strong" Multifunctionality: Conceptualising Farm-Level Multifunctional Transitional Pathways

    ERIC Educational Resources Information Center

    Wilson, Geoff A.

    2008-01-01

    Building on normative conceptualisations of multifunctionality as a decision-making spectrum bounded by productivist and non-productivist action and thought, this paper analyses farm-level multifunctional agricultural transitions. First, the paper suggests that it may be possible to categorise different farm types along the…

  19. Portable or Modular? There Is a Difference....

    ERIC Educational Resources Information Center

    Morton, Mike

    2002-01-01

    Describes differences between two types of school facilities: portable (prebuilt, temporary wood structure installed on site) and modular (method of construction for permanent buildings). Provides details of modular construction. (PKP)

  20. Multifunctional nanorods for gene delivery

    NASA Astrophysics Data System (ADS)

    Salem, Aliasger K.; Searson, Peter C.; Leong, Kam W.

    2003-10-01

    The goal of gene therapy is to introduce foreign genes into somatic cells to supplement defective genes or provide additional biological functions, and can be achieved using either viral or synthetic non-viral delivery systems. Compared with viral vectors, synthetic gene-delivery systems, such as liposomes and polymers, offer several advantages including ease of production and reduced risk of cytotoxicity and immunogenicity, but their use has been limited by the relatively low transfection efficiency. This problem mainly stems from the difficulty in controlling their properties at the nanoscale. Synthetic inorganic gene carriers have received limited attention in the gene-therapy community, the only notable example being gold nanoparticles with surface-immobilized DNA applied to intradermal genetic immunization by particle bombardment. Here we present a non-viral gene-delivery system based on multisegment bimetallic nanorods that can simultaneously bind compacted DNA plasmids and targeting ligands in a spatially defined manner. This approach allows precise control of composition, size and multifunctionality of the gene-delivery system. Transfection experiments performed in vitro and in vivo provide promising results that suggest potential in genetic vaccination applications.

  1. Multifunctional self-assembled monolayers

    SciTech Connect

    Zawodzinski, T.; Bar, G.; Rubin, S.; Uribe, F.; Ferrais, J.

    1996-06-01

    This is the final report of at three year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The specific goals of this research project were threefold: to develop multifunctional self-assembled monolayers, to understand the role of monolayer structure on the functioning of such systems, and to apply this knowledge to the development of electrochemical enzyme sensors. An array of molecules that can be used to attach electrochemically active biomolecules to gold surfaces has been synthesized. Several members of a class of electroactive compounds have been characterized and the factors controlling surface modification are beginning to be characterized. Enzymes have been attached to self-assembled molecules arranged on the gold surface, a critical step toward the ultimate goal of this project. Several alternative enzyme attachment strategies to achieve robust enzyme- modified surfaces have been explored. Several means of juxtaposing enzymes and mediators, electroactive compounds through which the enzyme can exchange electrons with the electrode surface, have also been investigated. Finally, the development of sensitive biosensors based on films loaded with nanoscale-supported gold particles that have surface modified with the self-assembled enzyme and mediator have been explored.

  2. 48 CFR 3417.70 - Modular contracting.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Modular contracting. 3417... REGULATION CONTRACTING METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Modular Contracting 3417.70 Modular contracting. (a) FSA—May incrementally conduct successive procurements of modules of...

  3. Evolution and the Modularity of Mindreading.

    ERIC Educational Resources Information Center

    Moore, Chris

    1996-01-01

    Reviews Baron-Cohen's study of autism and an explanatory theory called modularity of mindreading, which proposed a domain-specific modular psychological model based on evolutionary, developmental, psychopathological, and neurobiological considerations. Enumerates problems with the modularity approach and emphasized the evolution of domain general…

  4. The Modular Mind and Intrapersonal Communication Processes.

    ERIC Educational Resources Information Center

    Stacks, Don W.

    Based on a prior model on modularity of the brain, a new modular model of intrapersonal communication was developed which focuses on brain processing, encompassing both the structures and the functions of those structures in the creation of messages. The modular mind is a bio-social model of communication which presupposes a relationship between…

  5. Modularity in Cognition: Framing the Debate

    ERIC Educational Resources Information Center

    Barrett, H. Clark; Kurzban, Robert

    2006-01-01

    Modularity has been the subject of intense debate in the cognitive sciences for more than 2 decades. In some cases, misunderstandings have impeded conceptual progress. Here the authors identify arguments about modularity that either have been abandoned or were never held by proponents of modular views of the mind. The authors review arguments that…

  6. Modular Building Institute. 2003 Educational Showcase.

    ERIC Educational Resources Information Center

    Roman, Michael; Robert, Laurie; Reynolds, Pamela; Ulrey, Bill; Crawford, Doug; Shield, Tom; Soenksen, Steven

    "Commercial Modular Construction Magazine" regularly contains articles where the use of modular schools and classrooms is highlighted. This document contains a selection of those articles, including: (1) "Relocatable Classrooms Come of Age" (Michael Roman); (2) "Systems Building" (Laurie Robert); (3) "Realizing Modular's Merits" (Michael Roman);…

  7. Rapidly Deployed Modular Telemetry System

    NASA Technical Reports Server (NTRS)

    Varnavas, Kosta A. (Inventor); Sims, William Herbert, III (Inventor)

    2013-01-01

    The present invention is a telemetry system, and more specifically is a rapidly deployed modular telemetry apparatus which utilizes of SDR technology and the FPGA programming capability to reduce the number of hardware components and programming required to deploy a telemetry system.

  8. Induction in a Modular Learner.

    ERIC Educational Resources Information Center

    Carroll, Susanne E.

    2002-01-01

    Presents a theory of inductive learning--Autonomous Induction Theory--a form of induction that takes place within the autonomous and modular representational systems of the language faculty. Argues that Autonomous Induction Theory is constrained enough to be taken seriously as a plausible approach to explaining second language acquisition.…

  9. Multifunctional PEGylated nanoclusters for biomedical applications

    NASA Astrophysics Data System (ADS)

    Peng, Erwin; Choo, Eugene Shi Guang; Tan, Cherie Shi Hua; Tang, Xiaosheng; Sheng, Yang; Xue, Junmin

    2013-06-01

    A simple and versatile synthesis method to form water soluble multifunctional nanoclusters using polyethylene glycol (PEG) functionalized poly(maleic anhydride-alt-1-octadecene) amphiphilic brush copolymers (PMAO-g-PEG) was presented. Simply by tuning the core size and the initial nanocrystal concentration, manganese ferrite nanoparticles (MFNPs) were used to demonstrate the versatility of tuning the loading amount of the nanoclusters. The resultant nanoclusters were found to have a well-controlled spherical shape. When Zn-doped AgInS2 quantum dots (AIZS QDs) were loaded together with the MFNP nanocrystals, bi-functional nanoclusters with fluorescent and magnetic behaviors were obtained. Such bi-functional nanoclusters were also successfully demonstrated for cellular bio-imaging. Moreover, the presence of another type of nanocrystals together with MFNPs was found to have a negligible effect on the overall properties of the nanoclusters as demonstrated by the MR relaxivity test. From the time-dependent colloidal stability test, it was found that the presence of the PEG chain grafted onto PMAO was able to reduce protein adsorption onto the nanocluster surface. An in vitro study on NIH/3T3 demonstrated the biocompatibility of the nanoclusters. Such biocompatible and colloidally stable nanoclusters with an approximate size of 80-120 nm were suitable for both MRI and cell labeling applications.A simple and versatile synthesis method to form water soluble multifunctional nanoclusters using polyethylene glycol (PEG) functionalized poly(maleic anhydride-alt-1-octadecene) amphiphilic brush copolymers (PMAO-g-PEG) was presented. Simply by tuning the core size and the initial nanocrystal concentration, manganese ferrite nanoparticles (MFNPs) were used to demonstrate the versatility of tuning the loading amount of the nanoclusters. The resultant nanoclusters were found to have a well-controlled spherical shape. When Zn-doped AgInS2 quantum dots (AIZS QDs) were loaded together

  10. Modular Multi-Function Multi-Band Airborne Radio System (MFBARS). Volume 1: Executive summary

    NASA Astrophysics Data System (ADS)

    Reilly, R. A.; Ward, C. W.; Lee, A.; Schineller, R.; Clemens, A.; Robertson, W.; Rome, J.

    1981-10-01

    This report describes the results of the first two phases of the MFBARS radio architecture study. This study was aimed at establishing a cost effective and volume-conserving method of integrating tactical CNI avionics equipments. The goal was innovative integration of these systems, by a method which would allow the incorporation of new capabilities and which would take advantage of technological advances, both in-hand and projected within the near-term future (1985). Such integration is needed to reduce spiraling life cycle costs and to alleviate severe hardware space limitation problems in tactical aircraft. During Phase I, a set of viable MFBARS candidate architectures was developed, together with a cost evaluation of these with respect to a government-provided baseline of existing equipment, to allow meaningful comparisons. The three MFBARS architectures proposed during Phase I were keyed to a reasonable expectation of techniques and devices projected to be available when MFBARS advanced development would be initiated in the mide '80's. The three architectures provided a graduated increase in payoff potential with associated increases in technical risk. The Government then selected the most advanced of the three Phase I candidate system architectures for more detailed study.

  11. Modular Multi-Function Multi-Band Airborne Radio System (MFBARS). Volume 2: Detailed report

    NASA Astrophysics Data System (ADS)

    Reilly, R. A.; Ward, C. W.; Lee, A.; Schineller, R.; Clemens, A.; Robertson, W.; Rome, J.

    1981-06-01

    a top down, system oriented study of the selected system approach was conducted. System configuration details and performance parameters were refined. In addition, to minimize system development risk and to provide guidance on the best direction among which MFBARS should proceed, recommended plans were defined for development of the system and supporting technology. Emphasis is placed on the final recommended development plans.

  12. Some Endpoint Results for β-Generalized Weak Contractive Multifunctions

    PubMed Central

    Alikhani, H.; Gopal, D.; Miandaragh, M. A.; Rezapour, Sh.; Shahzad, N.

    2013-01-01

    We introduce β-generalized weak contractive multifunctions and give some results about endpoints of the multifunctions. Also, we give some results about role of a point in the existence of endpoints. PMID:24348197

  13. In vivo architectonic stability of fully de novo designed protein-only nanoparticles.

    PubMed

    Céspedes, María Virtudes; Unzueta, Ugutz; Tatkiewicz, Witold; Sánchez-Chardi, Alejandro; Conchillo-Solé, Oscar; Álamo, Patricia; Xu, Zhikun; Casanova, Isolda; Corchero, José Luis; Pesarrodona, Mireia; Cedano, Juan; Daura, Xavier; Ratera, Imma; Veciana, Jaume; Ferrer-Miralles, Neus; Vazquez, Esther; Villaverde, Antonio; Mangues, Ramón

    2014-05-27

    The fully de novo design of protein building blocks for self-assembling as functional nanoparticles is a challenging task in emerging nanomedicines, which urgently demand novel, versatile, and biologically safe vehicles for imaging, drug delivery, and gene therapy. While the use of viruses and virus-like particles is limited by severe constraints, the generation of protein-only nanocarriers is progressively reachable by the engineering of protein-protein interactions, resulting in self-assembling functional building blocks. In particular, end-terminal cationic peptides drive the organization of structurally diverse protein species as regular nanosized oligomers, offering promise in the rational engineering of protein self-assembling. However, the in vivo stability of these constructs, being a critical issue for their medical applicability, needs to be assessed. We have explored here if the cross-molecular contacts between protein monomers, generated by end-terminal cationic peptides and oligohistidine tags, are stable enough for the resulting nanoparticles to overcome biological barriers in assembled form. The analyses of renal clearance and biodistribution of several tagged modular proteins reveal long-term architectonic stability, allowing systemic circulation and tissue targeting in form of nanoparticulate material. This observation fully supports the value of the engineered of protein building blocks addressed to the biofabrication of smart, robust, and multifunctional nanoparticles with medical applicability that mimic structure and functional capabilities of viral capsids. PMID:24708510

  14. Modeling holo-ACP:DH and holo-ACP:KR complexes of modular polyketide synthases: a docking and molecular dynamics study

    PubMed Central

    2012-01-01

    Background Modular polyketide synthases are multifunctional megasynthases which biosynthesize a variety of secondary metabolites using various combinations of dehydratase (DH), ketoreductase (KR) and enoyl-reductase (ER) domains. During the catalysis of various reductive steps these domains act on a substrate moiety which is covalently attached to the phosphopantetheine (P-pant) group of the holo-Acyl Carrier Protein (holo-ACP) domain, thus necessitating the formation of holo-ACP:DH and holo-ACP:KR complexes. Even though three dimensional structures are available for DH, KR and ACP domains, no structures are available for DH or KR domains in complex with ACP or substrate moieties. Since Ser of holo-ACP is covalently attached to a large phosphopantetheine group, obtaining complexes involving holo-ACP by standard protein-protein docking has been a difficult task. Results We have modeled the holo-ACP:DH and holo-ACP:KR complexes for identifying specific residues on DH and KR domains which are involved in interaction with ACP, phosphopantetheine and substrate moiety. A novel combination of protein-protein and protein-ligand docking has been used to first model complexes involving apo-ACP and then dock the phosphopantetheine and substrate moieties using covalent connectivity between ACP, phosphopantetheine and substrate moiety as constraints. The holo-ACP:DH and holo-ACP:KR complexes obtained from docking have been further refined by restraint free explicit solvent MD simulations to incorporate effects of ligand and receptor flexibilities. The results from 50 ns MD simulations reveal that substrate enters into a deep tunnel in DH domain while in case of KR domain the substrate binds a shallow surface exposed cavity. Interestingly, in case of DH domain the predicted binding site overlapped with the binding site in the inhibitor bound crystal structure of FabZ, the DH domain from E.Coli FAS. In case of KR domain, the substrate binding site identified by our simulations

  15. Modularity and stability in ecological communities

    PubMed Central

    Grilli, Jacopo; Rogers, Tim; Allesina, Stefano

    2016-01-01

    Networks composed of distinct, densely connected subsystems are called modular. In ecology, it has been posited that a modular organization of species interactions would benefit the dynamical stability of communities, even though evidence supporting this hypothesis is mixed. Here we study the effect of modularity on the local stability of ecological dynamical systems, by presenting new results in random matrix theory, which are obtained using a quaternionic parameterization of the cavity method. Results show that modularity can have moderate stabilizing effects for particular parameter choices, while anti-modularity can greatly destabilize ecological networks. PMID:27337386

  16. The multifunctional SNM1 gene family: not just nucleases

    PubMed Central

    Yan, Yiyi; Akhter, Shamima; Zhang, Xiaoshan; Legerski, Randy

    2010-01-01

    The archetypical member of the SNM1 gene family was discovered 30 years ago in the budding yeast Saccharomyces cerevisiae. This small but ubiquitous gene family is characterized by metallo-β-lactamase and β-CASP domains, which together have been demonstrated to comprise a nuclease activity. Three mammalian members of this family, SNM1A, SNM1B/Apollo and Artemis, have been demonstrated to play surprisingly divergent roles in cellular metabolism. These pathways include variable (diversity) joining recombination, nonhomologous end-joining of double-strand breaks, DNA damage and mitotic cell cycle checkpoints, telomere maintenance and protein ubiquitination. Not all of these functions are consistent with a model in which these proteins act only as nucleases, and indicate that the SNM1 gene family encodes multifunctional products that can act in diverse biochemical pathways. In this article we discuss the various functions of SNM1A, SNM1B/Apollo and Artemis. PMID:20528238

  17. Multifunctional materials for bone cancer treatment

    PubMed Central

    Marques, Catarina; Ferreira, José MF; Andronescu, Ecaterina; Ficai, Denisa; Sonmez, Maria; Ficai, Anton

    2014-01-01

    The purpose of this review is to present the most recent findings in bone tissue engineering. Special attention is given to multifunctional materials based on collagen and collagen–hydroxyapatite composites used for skin and bone cancer treatments. The multi-functionality of these materials was obtained by adding to the base regenerative grafts proper components, such as ferrites (magnetite being the most important representative), cytostatics (cisplatin, carboplatin, vincristine, methotrexate, paclitaxel, doxorubicin), silver nanoparticles, antibiotics (anthracyclines, geldanamycin), and/or analgesics (ibuprofen, fentanyl). The suitability of complex systems for the intended applications was systematically analyzed. The developmental possibilities of multifunctional materials with regenerative and curative roles (antitumoral as well as pain management) in the field of skin and bone cancer treatment are discussed. It is worth mentioning that better materials are likely to be developed by combining conventional and unconventional experimental strategies. PMID:24920907

  18. Modular Automated Processing System (MAPS) for analysis of biological samples.

    SciTech Connect

    Gil, Geun-Cheol; Chirica, Gabriela S.; Fruetel, Julia A.; VanderNoot, Victoria A.; Branda, Steven S.; Schoeniger, Joseph S.; Throckmorton, Daniel J.; Brennan, James S.; Renzi, Ronald F.

    2010-10-01

    We have developed a novel modular automated processing system (MAPS) that enables reliable, high-throughput analysis as well as sample-customized processing. This system is comprised of a set of independent modules that carry out individual sample processing functions: cell lysis, protein concentration (based on hydrophobic, ion-exchange and affinity interactions), interferent depletion, buffer exchange, and enzymatic digestion of proteins of interest. Taking advantage of its unique capacity for enclosed processing of intact bioparticulates (viruses, spores) and complex serum samples, we have used MAPS for analysis of BSL1 and BSL2 samples to identify specific protein markers through integration with the portable microChemLab{trademark} and MALDI.

  19. Complex Multifunctional Polymer/Carbon-Nanotube Composites

    NASA Technical Reports Server (NTRS)

    Patel, Pritesh; Balasubramaniyam, Gobinath; Chen, Jian

    2009-01-01

    A methodology for developing complex multifunctional materials that consist of or contain polymer/carbon-nanotube composites has been conceived. As used here, "multifunctional" signifies having additional and/or enhanced physical properties that polymers or polymer-matrix composites would not ordinarily be expected to have. Such properties include useful amounts of electrical conductivity, increased thermal conductivity, and/or increased strength. In the present methodology, these properties are imparted to a given composite through the choice and processing of its polymeric and CNT constituents.

  20. Multifunctional Nucleic Acids for Tumor Cell Treatment

    PubMed Central

    Pofahl, Monika; Wengel, Jesper

    2014-01-01

    We report on a multifunctional nucleic acid, termed AptamiR, composed of an aptamer domain and an antimiR domain. This composition mediates cell specific delivery of antimiR molecules for silencing of endogenous micro RNA. The introduced multifunctional molecule preserves cell targeting, anti-proliferative and antimiR function in one 37-nucleotide nucleic acid molecule. It inhibits cancer cell growth and induces gene expression that is pathologically damped by an oncomir. These findings will have a strong impact on future developments regarding aptamer- and antimiR-related applications for tumor targeting and treatment. PMID:24494617

  1. Novel hybrid multifunctional magnetoelectric porous composite films

    NASA Astrophysics Data System (ADS)

    Martins, P.; Gonçalves, R.; Lopes, A. C.; Venkata Ramana, E.; Mendiratta, S. K.; Lanceros-Mendez, S.

    2015-12-01

    Novel multifunctional porous films have been developed by the integration of magnetic CoFe2O4 (CFO) nanoparticles into poly(vinylidene fluoride)-Trifuoroethylene (P(VDF-TrFE)), taking advantage of the synergies of the magnetostrictive filler and the piezoelectric polymer. The porous films show a piezoelectric response with an effective d33 coefficient of -22 pC/N-1, a maximum magnetization of 12 emu g-1 and a maximum magnetoelectric coefficient of 9 mV cm-1 Oe-1. In this way, a multifunctional membrane has been developed suitable for advanced applications ranging from biomedical to water treatment.

  2. Modular hydrodam: concept definition study

    SciTech Connect

    Not Available

    1981-07-01

    The purpose of this investigation was to explore the potential for developing economical new ultra low-head (6 to 10 ft) sites using an innovative concept known as the Modular Hydrodam (MH). This concept combines the benefits of shop fabrication, installation of equipment in truck transportable, waterproof power modules, and prefabricated gate sections that can be located between the power modules. The size and weight of the power module permits it to be fully assembled and checked out in the manufacturer's shop. The module can then be broken down into four pieces and shipped by truck to the site. Once in place, concrete ballast will be added, as necessary, to prevent flotation. The following aspects were investigated: tubular and cross flow turbines; modularized components; the use of a cable support system for horizontal stability of the dam and powerhouse; and construction in the wet as well as in the dry.

  3. Modular Stellarator Fusion Reactor concept

    SciTech Connect

    Miller, R.L.; Krakowski, R.A.

    1981-08-01

    A preliminary conceptual study is made of the Modular Stellarator Reactor (MSR). A steady-state ignited, DT-fueled, magnetic fusion reactor is proposed for use as a central electric-power station. The MSR concept combines the physics of the classic stellarator confinement topology with an innovative, modular-coil design. Parametric tradeoff calculations are described, leading to the selection of an interim design point for a 4-GWt plant based on Alcator transport scaling and an average beta value of 0.04 in an l = 2 system with a plasma aspect ratio of 11. The physics basis of the design point is described together with supporting magnetics, coil-force, and stress computations. The approach and results presented herein will be modified in the course of ongoing work to form a firmer basis for a detailed conceptual design of the MSR.

  4. Multifunctional Upconversion-Magnetic Hybrid Nanostructured Materials: Synthesis and Bioapplications

    PubMed Central

    Li, Xiaomin; Zhao, Dongyuan; Zhang, Fan

    2013-01-01

    The combination of nanotechnology and biology has developed into an emerging research area: nano-biotechnology. Upconversion nanoparticles (UCNPs) have attracted a great deal of attention in bioapplications due to their high chemical stability, low toxicity, and high signal-to-noise ratio. Magnetic nanoparticles (MNPs) are also well-established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI). As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging. Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional upconversion-magnetic hybrid nanostructured materials. The hybrid nanostructures, which combine UCNPs with MNPs, exhibit upconversion fluorescence alongside superparamagnetism property. Such structures could provide a platform for enhanced bioimaging and controlled drug delivery. We expect that the combination of unique structural characteristics and integrated functions of multifunctional upconversion-magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nano-bioapplications. PMID:23650477

  5. Poly(3-hydroxybutyrate) multifunctional composite scaffolds for tissue engineering applications.

    PubMed

    Misra, Superb K; Ansari, Tahera I; Valappil, Sabeel P; Mohn, Dirk; Philip, Sheryl E; Stark, Wendelin J; Roy, Ipsita; Knowles, Jonathan C; Salih, Vehid; Boccaccini, Aldo R

    2010-04-01

    Poly(3-hydroxybutyrate) (P(3HB)) foams exhibiting highly interconnected porosity (85% porosity) were prepared using a unique combination of solvent casting and particulate leaching techniques by employing commercially available sugar cubes as porogen. Bioactive glass (BG) particles of 45S5 Bioglass grade were introduced in the scaffold microstructure, both in micrometer ((m-BG), <5 microm) and nanometer ((n-BG), 30 nm) sizes. The in vitro bioactivity of the P(3HB)/BG foams was confirmed within 10 days of immersion in simulated body fluid and the foams showed high level of protein adsorption. The foams interconnected porous microstructure proved to be suitable for MG-63 osteoblast cell attachment and proliferation. The foams implanted in rats as subcutaneous implants resulted in a non-toxic and foreign body response after one week of implantation. In addition to showing bioactivity and biocompatibility, the P(3HB)/BG composite foams also exhibited bactericidal properties, which was tested on the growth of Staphylococcus aureus. An attempt was made at developing multifunctional scaffolds by incorporating, in addition to BG, selected concentrations of Vitamin E or/and carbon nanotubes. P(3HB) scaffolds with multifunctionalities (viz. bactericidal, bioactive, electrically conductive, antioxidative behaviour) were thus produced, which paves the way for next generation of advanced scaffolds for bone tissue engineering. PMID:20045554

  6. CAMAC modular programmable function generator

    SciTech Connect

    Turner, G.W.; Suehiro, S.; Hendricks, R.W.

    1980-12-01

    A CAMAC modular programmable function generator has been developed. The device contains a 1024 word by 12-bit memory, a 12-bit digital-to-analog converter with a 600 ns settling time, an 18-bit programmable frequency register, and two programmable trigger output registers. The trigger registers can produce programmed output logic transitions at various (binary) points in the output function curve, and are used to synchronize various other data acquisition devices with the function curve.

  7. High density modular avionics packaging

    NASA Astrophysics Data System (ADS)

    Poradish, F.

    Requirements and design configurations for high density modular avionics packaging are examined, with particular attention given to new hardware trends, the design of high-density standard modules (HDSM's), and HDSM requirements. The discussion of the HDSM's covers thermal management, system testability, power supply, and performance specifications. The general design of an integrated HDSM demonstration system currently under construction is briefly described, and some test data are presented.

  8. Multidimensional bioseparation with modular microfluidics

    DOEpatents

    Chirica, Gabriela S.; Renzi, Ronald F.

    2013-08-27

    A multidimensional chemical separation and analysis system is described including a prototyping platform and modular microfluidic components capable of rapid and convenient assembly, alteration and disassembly of numerous candidate separation systems. Partial or total computer control of the separation system is possible. Single or multiple alternative processing trains can be tested, optimized and/or run in parallel. Examples related to the separation and analysis of human bodily fluids are given.

  9. Deinterlacing using modular neural network

    NASA Astrophysics Data System (ADS)

    Woo, Dong H.; Eom, Il K.; Kim, Yoo S.

    2004-05-01

    Deinterlacing is the conversion process from the interlaced scan to progressive one. While many previous algorithms that are based on weighted-sum cause blurring in edge region, deinterlacing using neural network can reduce the blurring through recovering of high frequency component by learning process, and is found robust to noise. In proposed algorithm, input image is divided into edge and smooth region, and then, to each region, one neural network is assigned. Through this process, each neural network learns only patterns that are similar, therefore it makes learning more effective and estimation more accurate. But even within each region, there are various patterns such as long edge and texture in edge region. To solve this problem, modular neural network is proposed. In proposed modular neural network, two modules are combined in output node. One is for low frequency feature of local area of input image, and the other is for high frequency feature. With this structure, each modular neural network can learn different patterns with compensating for drawback of counterpart. Therefore it can adapt to various patterns within each region effectively. In simulation, the proposed algorithm shows better performance compared with conventional deinterlacing methods and single neural network method.

  10. Several scales of biodiversity affect ecosystem multifunctionality.

    PubMed

    Pasari, Jae R; Levi, Taal; Zavaleta, Erika S; Tilman, David

    2013-06-18

    Society values landscapes that reliably provide many ecosystem functions. As the study of ecosystem functioning expands to include more locations, time spans, and functions, the functional importance of individual species is becoming more apparent. However, the functional importance of individual species does not necessarily translate to the functional importance of biodiversity measured in whole communities of interacting species. Furthermore, ecological diversity at scales larger than neighborhood species richness could also influence the provision of multiple functions over extended time scales. We created experimental landscapes based on whole communities from the world's longest running biodiversity-functioning field experiment to investigate how local species richness (α diversity), distinctness among communities (β diversity), and larger scale species richness (γ diversity) affected eight ecosystem functions over 10 y. Using both threshold-based and unique multifunctionality metrics, we found that α diversity had strong positive effects on most individual functions and multifunctionality, and that positive effects of β and γ diversity emerged only when multiple functions were considered simultaneously. Higher β diversity also reduced the variability in multifunctionality. Thus, in addition to conserving important species, maintaining ecosystem multifunctionality will require diverse landscape mosaics of diverse communities. PMID:23733963

  11. Brain and language: evidence for neural multifunctionality.

    PubMed

    Cahana-Amitay, Dalia; Albert, Martin L

    2014-01-01

    This review paper presents converging evidence from studies of brain damage and longitudinal studies of language in aging which supports the following thesis: the neural basis of language can best be understood by the concept of neural multifunctionality. In this paper the term "neural multifunctionality" refers to incorporation of nonlinguistic functions into language models of the intact brain, reflecting a multifunctional perspective whereby a constant and dynamic interaction exists among neural networks subserving cognitive, affective, and praxic functions with neural networks specialized for lexical retrieval, sentence comprehension, and discourse processing, giving rise to language as we know it. By way of example, we consider effects of executive system functions on aspects of semantic processing among persons with and without aphasia, as well as the interaction of executive and language functions among older adults. We conclude by indicating how this multifunctional view of brain-language relations extends to the realm of language recovery from aphasia, where evidence of the influence of nonlinguistic factors on the reshaping of neural circuitry for aphasia rehabilitation is clearly emerging. PMID:25009368

  12. Modular open RF architecture: extending VICTORY to RF systems

    NASA Astrophysics Data System (ADS)

    Melber, Adam; Dirner, Jason; Johnson, Michael

    2015-05-01

    Radio frequency products spanning multiple functions have become increasingly critical to the warfighter. Military use of the electromagnetic spectrum now includes communications, electronic warfare (EW), intelligence, and mission command systems. Due to the urgent needs of counterinsurgency operations, various quick reaction capabilities (QRCs) have been fielded to enhance warfighter capability. Although these QRCs were highly successfully in their respective missions, they were designed independently resulting in significant challenges when integrated on a common platform. This paper discusses how the Modular Open RF Architecture (MORA) addresses these challenges by defining an open architecture for multifunction missions that decomposes monolithic radio systems into high-level components with welldefined functions and interfaces. The functional decomposition maximizes hardware sharing while minimizing added complexity and cost due to modularization. MORA achieves significant size, weight and power (SWaP) savings by allowing hardware such as power amplifiers and antennas to be shared across systems. By separating signal conditioning from the processing that implements the actual radio application, MORA exposes previously inaccessible architecture points, providing system integrators with the flexibility to insert third-party capabilities to address technical challenges and emerging requirements. MORA leverages the Vehicular Integration for Command, Control, Communication, Computers, Intelligence, Surveillance, and Reconnaissance (C4ISR)/EW Interoperability (VICTORY) framework. This paper concludes by discussing how MORA, VICTORY and other standards such as OpenVPX are being leveraged by the U.S. Army Research, Development, and Engineering Command (RDECOM) Communications Electronics Research, Development, and Engineering Center (CERDEC) to define a converged architecture enabling rapid technology insertion, interoperability and reduced SWaP.

  13. Engineering biodegradable and multifunctional peptide-based polymers for gene delivery

    PubMed Central

    2013-01-01

    The complex nature of in vivo gene transfer establishes the need for multifunctional delivery vectors capable of meeting these challenges. An additional consideration for clinical translation of synthetic delivery formulations is reproducibility and scale-up of materials. In this review, we summarize our work over the last five years in developing a modular approach for synthesizing peptide-based polymers. In these materials, bioactive peptides that address various barriers to gene delivery are copolymerized with a hydrophilic backbone of N-(2-hydroxypropyl)methacrylamide (HPMA) using reversible-addition fragmentation chain-transfer (RAFT) polymerization. We demonstrate that this synthetic approach results in well-defined, narrowly-disperse polymers with controllable composition and molecular weight. To date, we have investigated the effectiveness of various bioactive peptides for DNA condensation, endosomal escape, cell targeting, and degradability on gene transfer, as well as the impact of multivalency and polymer architecture on peptide bioactivity. PMID:24156736

  14. Modular microrobot for swimming in heterogeneous environments

    NASA Astrophysics Data System (ADS)

    Cheang, U. Kei; Meshkati, Meshkati; Fu, Henry; Kim, Minjun; Drexel University Team; University of Nevada, Reno Team

    2015-11-01

    One of the difficulties in navigating in vivo is to overcome many types of environments. This includes blood vessels of different diameters, fluids with different mechanical properties, and physical barriers. Inspired by conventional modular robotics, we demonstrate modular microrobotics using magnetic particles as the modular units to change size and shape through docking and undocking. Much like the vast variety of microorganisms navigating many different bio-environments, modular microswimmers have the ability to dynamically adapt different environments by reconfiguring the swimmers' physical characteristics. We model the docking as magnetic assembly and undocking mechanisms as deformation by hydrodynamic forces. We characterize the swimming capability of the modular microswimmer with different size and shapes. Finally, we demonstrate modular microrobotics by assembling a three-bead microswimmer into a nine-bead microswimmer, and then disassemble it into several independently swimming microswimmers..

  15. Multifunctional, High-Temperature Nanocomposites

    NASA Technical Reports Server (NTRS)

    Connell, John W.; Smith, Joseph G.; Siochi, Emilie J.; Working, Dennis C.; Criss, Jim M.; Watson, Kent A.; Delozier, Donavon M.; Ghose, Sayata

    2007-01-01

    In experiments conducted as part of a continuing effort to incorporate multifunctionality into advanced composite materials, blends of multi-walled carbon nanotubes and a resin denoted gPETI-330 h (wherein gPETI h is an abbreviation for gphenylethynyl-terminated imide h) were prepared, characterized, and fabricated into moldings. PETI-330 was selected as the matrix resin in these experiments because of its low melt viscosity (<10 poise at a temperature of 280 C), excellent melt stability (lifetime >2 hours at 280 C), and high temperature performance (>1,000 hours at 288 C). The multi-walled carbon nanotubes (MWCNTs), obtained from the University of Kentucky, were selected because of their electrical and thermal conductivity and their small diameters. The purpose of these experiments was to determine the combination of thermal, electrical, and mechanical properties achievable while still maintaining melt processability. The PETI-330/MWCNT mixtures were prepared at concentrations ranging from 3 to 25 weight-percent of MWCNTs by dry mixing of the constituents in a ball mill using zirconia beads. The resulting powders were characterized for degree of mixing and thermal and rheological properties. The neat resin was found to have melt viscosity between 5 and 10 poise. At 280 C and a fixed strain rate, the viscosity was found to increase with time. At this temperature, the phenylethynyl groups do not readily react and so no significant curing of the resin occurred. For MWCNT-filled samples, melt viscosity was reasonably steady at 280 C and was greater in samples containing greater proportions of MWCNTs. The melt viscosity for 20 weightpercent of MWCNTs was found to be .28,000 poise, which is lower than the initial estimated allowable maximum value of 60,000 poise for injection molding. Hence, MWCNT loadings of as much as 20 percent were deemed to be suitable compositions for scale-up. High-resolution scanning electron microscopy (HRSEM) showed the MWCNTs to be well

  16. Magnetically Attached Multifunction Maintenance Rover

    NASA Technical Reports Server (NTRS)

    Bar-Cohen, Yoseph; Joffe, Benjamin

    2005-01-01

    A versatile mobile telerobot, denoted the magnetically attached multifunction maintenance rover (MAGMER), has been proposed for use in the inspection and maintenance of the surfaces of ships, tanks containing petrochemicals, and other large ferromagnetic structures. As its name suggests, this robot would utilize magnetic attraction to adhere to a structure. As it moved along the surface of the structure, the MAGMER would perform tasks that could include close-up visual inspection by use of video cameras, various sensors, and/or removal of paint by water-jet blasting, laser heating, or induction heating. The water-jet nozzles would be mounted coaxially within compressed-air-powered venturi nozzles that would collect the paint debris dislodged by the jets. The MAGMER would be deployed, powered, and controlled from a truck, to which it would be connected by hoses for water, compressed air, and collection of debris and by cables for electric power and communication (see Figure 1). The operation of the MAGMER on a typical large structure would necessitate the use of long cables and hoses, which can be heavy. To reduce the load of the hoses and cables on the MAGMER and thereby ensure its ability to adhere to vertical and overhanging surfaces, the hoses and cables would be paid out through telescopic booms that would be parts of a MAGMER support system. The MAGMER would move by use of four motorized, steerable wheels, each of which would be mounted in an assembly that would include permanent magnets and four pole pieces (see Figure 2). The wheels would protrude from between the pole pieces by only about 3 mm, so that the gap between the pole pieces and the ferromagnetic surface would be just large enough to permit motion along the surface but not so large as to reduce the magnetic attraction excessively. In addition to the wheel assemblies, the MAGMER would include magnetic adherence enhancement fixtures, which would comprise arrays of permanent magnets and pole pieces

  17. Intelligent CAD approach for modular design

    NASA Astrophysics Data System (ADS)

    Ouyang, Miao-an; Li, Chenggang; Zhong, Yifang; Yu, Jun; Zhou, Ji

    1996-03-01

    In this paper, the technology of Artificial Intelligence is introduced into a modular design and manufacturing for machine tools. The authors present a methodology to realize the modular conceptual design combined with traditional CAD, and develop an intelligent machine tools modular conceptual system. The problem-solving strategies are described in detail. The design model and system architecture are set up. Techniques and their incorporation of expert system, case-based reasoning and artificial neural networks are clarified.

  18. Modular, Hierarchical Learning By Artificial Neural Networks

    NASA Technical Reports Server (NTRS)

    Baldi, Pierre F.; Toomarian, Nikzad

    1996-01-01

    Modular and hierarchical approach to supervised learning by artificial neural networks leads to neural networks more structured than neural networks in which all neurons fully interconnected. These networks utilize general feedforward flow of information and sparse recurrent connections to achieve dynamical effects. The modular organization, sparsity of modular units and connections, and fact that learning is much more circumscribed are all attractive features for designing neural-network hardware. Learning streamlined by imitating some aspects of biological neural networks.

  19. Juggling jobs: roles and mechanisms of multifunctional protease inhibitors in plants.

    PubMed

    Grosse-Holz, Friederike M; van der Hoorn, Renier A L

    2016-05-01

    Multifunctional protease inhibitors juggle jobs by targeting different enzymes and thereby often controlling more than one biological process. Here, we discuss the biological functions, mechanisms and evolution of three types of multifunctional protease inhibitors in plants. The first type is double-headed inhibitors, which feature two inhibitory sites targeting proteases with different specificities (e.g. Bowman-Birk inhibitors) or even different hydrolases (e.g. α-amylase/protease inhibitors preventing both early germination and seed predation). The second type consists of multidomain inhibitors which evolved by intragenic duplication and are released by processing (e.g. multicystatins and potato inhibitor II, implicated in tuber dormancy and defence, respectively). The third type consists of promiscuous inhibitory folds which resemble mouse traps that can inhibit different proteases cleaving the bait they offer (e.g. serpins, regulating cell death, and α-macroglobulins). Understanding how multifunctional inhibitors juggle biological jobs increases our knowledge of the connections between the networks they regulate. These examples show that multifunctionality evolved independently from a remarkable diversity of molecular mechanisms that can be exploited for crop improvement and provide concepts for protein design. PMID:26800491

  20. Multifunctional targeting vinorelbine plus tetrandrine liposomes for treating brain glioma along with eliminating glioma stem cells.

    PubMed

    Li, Xue-Tao; Tang, Wei; Jiang, Ying; Wang, Xiao-Min; Wang, Yan-Hong; Cheng, Lan; Meng, Xian-Sheng

    2016-04-26

    Malignant brain glioma is the most lethal and aggressive type of cancer. Surgery and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood-brain barrier (BBB) restricts the movement of antitumor drugs from blood to brain, thus leading to the poor prognosis with high recurrence rate. In the present study, the targeting conjugates of cholesterol polyethylene glycol polyethylenimine (CHOL-PEG2000-PEI) and D-a-tocopheryl polyethylene glycol 1000 succinate vapreotide (TPGS1000-VAP) were newly synthesized for transporting drugs across the BBB and targeting glioma cells and GSCs. The multifunctional targeting vinorelbine plus tetrandrine liposomes were constructed by modifying the targeting conjugates. The studies were undertaken on BBB model, glioma cells, GSCs, and glioma-bearing mice. In vitro results showed that multifunctional targeting drugs-loaded liposomes with suitable physicochemical property could enhance the transport drugs across the BBB, increase the intracellular uptake, inhibit glioma cells and GSCs, penetrate and destruct the GSCs spheroids, and induce apoptosis via activating related apoptotic proteins. In vivo results demonstrated that multifunctional targeting drugs-loaded liposomes could significantly accumulate into brain tumor location, show the specificity to tumor sites, and result in a robust overall antitumor efficacy in glioma-bearing mice. These data suggested that the multifunctional targeting vinorelbine plus tetrandrine liposomes could offer a promising strategy for treating brain glioma. PMID:27029055

  1. High performance backplane components for modular avionics

    NASA Astrophysics Data System (ADS)

    Groves-Kirkby, C. J.; Goodwin, M. J.; Hall, J. P.; Glynn, G.; Hankey, J.; Salik, M. D.; Goodfellow, R. C.; Jibb, D. J.

    1994-10-01

    The design and development of optoelectronic transceiver and optical pathway components for application in a modular avionics backplane demonstrator system are described and initial performance results are presented.

  2. Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling.

    PubMed

    Wu, Yuteng; Olsen, Lasse B; Lau, Yu Heng; Jensen, Claus Hatt; Rossmann, Maxim; Baker, Ysobel R; Sore, Hannah F; Collins, Súil; Spring, David R

    2016-04-15

    Photoaffinity labelling is a useful method for studying how proteins interact with ligands and biomolecules, and can help identify and characterise new targets for the development of new therapeutics. We present the design and synthesis of a novel multifunctional benzophenone linker that serves as both a photo-crosslinking motif and a peptide stapling reagent. Using double-click stapling, we attached the benzophenone to the peptide via the staple linker, rather than by modifying the peptide sequence with a photo-crosslinking amino acid. When applied to a p53-derived peptide, the resulting photoreactive stapled peptide was able to preferentially crosslink with MDM2 in the presence of competing protein. This multifunctional linker also features an extra alkyne handle for downstream applications such as pull-down assays, and can be used to investigate the target selectivity of stapled peptides. PMID:26919579

  3. Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling

    PubMed Central

    Wu, Yuteng; Olsen, Lasse B.; Lau, Yu Heng; Jensen, Claus Hatt; Rossmann, Maxim; Baker, Ysobel R.; Sore, Hannah F.; Collins, Súil

    2016-01-01

    Abstract Photoaffinity labelling is a useful method for studying how proteins interact with ligands and biomolecules, and can help identify and characterise new targets for the development of new therapeutics. We present the design and synthesis of a novel multifunctional benzophenone linker that serves as both a photo‐crosslinking motif and a peptide stapling reagent. Using double‐click stapling, we attached the benzophenone to the peptide via the staple linker, rather than by modifying the peptide sequence with a photo‐crosslinking amino acid. When applied to a p53‐derived peptide, the resulting photoreactive stapled peptide was able to preferentially crosslink with MDM2 in the presence of competing protein. This multifunctional linker also features an extra alkyne handle for downstream applications such as pull‐down assays, and can be used to investigate the target selectivity of stapled peptides. PMID:26919579

  4. Modular design attitude control system

    NASA Technical Reports Server (NTRS)

    Chichester, F. D.

    1984-01-01

    A sequence of single axismodels and a series of reduced state linear observers of minimum order are used to reconstruct inaccessible variables pertaining to the modular attitude control of a rigid body flexible suspension model of a flexible spacecraft. The single axis models consist of two, three, four, and five rigid bodies, each interconnected by a flexible shaft passing through the mass centers of the bodies. Modal damping is added to each model. Reduced state linear observers are developed for synthesizing the inaccessible modal state variables for each modal model.

  5. Modularized construction of general integrated circuits on individual carbon nanotubes.

    PubMed

    Pei, Tian; Zhang, Panpan; Zhang, Zhiyong; Qiu, Chenguang; Liang, Shibo; Yang, Yingjun; Wang, Sheng; Peng, Lian-Mao

    2014-06-11

    While constructing general integrated circuits (ICs) with field-effect transistors (FETs) built on individual CNTs is among few viable ways to build ICs with small dimension and high performance that can be compared with that of state-of-the-art Si based ICs, this has not been demonstrated owing to the absence of valid and well-tolerant fabrication method. Here we demonstrate a modularized method for constructing general ICs on individual CNTs with different electric properties. A pass-transistor-logic style 8-transistor (8-T) unit is built, demonstrated as a multifunctional function generator with good tolerance to inhomogeneity in the CNTs used and used as a building block for constructing general ICs. As an example, an 8-bits BUS system that is widely used to transfer data between different systems in a computer is constructed. This is the most complicated IC fabricated on individual CNTs to date, containing 46 FETs built on six individual semiconducting CNTs. The 8-T unit provides a good basis for constructing complex ICs to explore the potential and limits of CNT ICs given the current imperfection in available CNT materials and may also be developed into a universal and efficient way for constructing general ICs on ideal CNT materials in the future. PMID:24796796

  6. Multifunctional facets of retrovirus integrase

    PubMed Central

    Grandgenett, Duane P; Pandey, Krishan K; Bera, Sibes; Aihara, Hideki

    2015-01-01

    The retrovirus integrase (IN) is responsible for integration of the reverse transcribed linear cDNA into the host DNA genome. First, IN cleaves a dinucleotide from the 3’ OH blunt ends of the viral DNA exposing the highly conserved CA sequence in the recessed ends. IN utilizes the 3’ OH ends to catalyze the concerted integration of the two ends into opposite strands of the cellular DNA producing 4 to 6 bp staggered insertions, depending on the retrovirus species. The staggered ends are repaired by host cell machinery that results in a permanent copy of the viral DNA in the cellular genome. Besides integration, IN performs other functions in the replication cycle of several studied retroviruses. The proper organization of IN within the viral internal core is essential for the correct maturation of the virus. IN plays a major role in reverse transcription by interacting directly with the reverse transcriptase and by binding to the viral capsid protein and a cellular protein. Recruitment of several other host proteins into the viral particle are also promoted by IN. IN assists with the nuclear transport of the preintegration complex across the nuclear membrane. With several retroviruses, IN specifically interacts with different host protein factors that guide the preintegration complex to preferentially integrate the viral genome into specific regions of the host chromosomal target. Human gene therapy using retrovirus vectors is directly affected by the interactions of IN with these host factors. Inhibitors directed against the human immunodeficiency virus (HIV) IN bind within the active site of IN containing viral DNA ends thus preventing integration and subsequent HIV/AIDS. PMID:26322168

  7. Multifunctional facets of retrovirus integrase.

    PubMed

    Grandgenett, Duane P; Pandey, Krishan K; Bera, Sibes; Aihara, Hideki

    2015-08-26

    The retrovirus integrase (IN) is responsible for integration of the reverse transcribed linear cDNA into the host DNA genome. First, IN cleaves a dinucleotide from the 3' OH blunt ends of the viral DNA exposing the highly conserved CA sequence in the recessed ends. IN utilizes the 3' OH ends to catalyze the concerted integration of the two ends into opposite strands of the cellular DNA producing 4 to 6 bp staggered insertions, depending on the retrovirus species. The staggered ends are repaired by host cell machinery that results in a permanent copy of the viral DNA in the cellular genome. Besides integration, IN performs other functions in the replication cycle of several studied retroviruses. The proper organization of IN within the viral internal core is essential for the correct maturation of the virus. IN plays a major role in reverse transcription by interacting directly with the reverse transcriptase and by binding to the viral capsid protein and a cellular protein. Recruitment of several other host proteins into the viral particle are also promoted by IN. IN assists with the nuclear transport of the preintegration complex across the nuclear membrane. With several retroviruses, IN specifically interacts with different host protein factors that guide the preintegration complex to preferentially integrate the viral genome into specific regions of the host chromosomal target. Human gene therapy using retrovirus vectors is directly affected by the interactions of IN with these host factors. Inhibitors directed against the human immunodeficiency virus (HIV) IN bind within the active site of IN containing viral DNA ends thus preventing integration and subsequent HIV/AIDS. PMID:26322168

  8. Acyrthosiphon pisum AQP2: a multifunctional insect aquaglyceroporin.

    PubMed

    Wallace, Ian S; Shakesby, Ally J; Hwang, Jin Ha; Choi, Won Gyu; Martínková, Natália; Douglas, Angela E; Roberts, Daniel M

    2012-03-01

    Annotation of the recently sequenced genome of the pea aphid (Acyrthosiphon pisum) identified a gene ApAQP2 (ACYPI009194, Gene ID: 100168499) with homology to the Major Intrinsic Protein/aquaporin superfamily of membrane channel proteins. Phylogenetic analysis suggests that ApAQP2 is a member of an insect-specific clade of this superfamily. Homology model structures of ApAQP2 showed a novel array of amino acids comprising the substrate selectivity-determining "aromatic/arginine" region of the putative transport pore. Subsequent characterization of the transport properties of ApAQP2 upon expression in Xenopus oocytes supports an unusual substrate selectivity profile. Water permeability analyses show that the ApAQP2 protein exhibits a robust mercury-insensitive aquaporin activity. However unlike the water-specific ApAQP1 protein, ApAQP2 forms a multifunctional transport channel that shows a wide permeability profile to a range of linear polyols, including the potentially biologically relevant substrates glycerol, mannitol and sorbitol. Gene expression analysis indicates that ApAQP2 is highly expressed in the insect bacteriocytes (cells bearing the symbiotic bacteria Buchnera) and the fat body. Overall the results demonstrate that ApAQP2 is a novel insect aquaglyceroporin which may be involved in water and polyol transport in support of the Buchnera symbiosis and aphid osmoregulation. PMID:22166843

  9. Modular evolution of phosphorylation-based signalling systems.

    PubMed

    Jin, Jing; Pawson, Tony

    2012-09-19

    Phosphorylation sites are formed by protein kinases ('writers'), frequently exert their effects following recognition by phospho-binding proteins ('readers') and are removed by protein phosphatases ('erasers'). This writer-reader-eraser toolkit allows phosphorylation events to control a broad range of regulatory processes, and has been pivotal in the evolution of new functions required for the development of multi-cellular animals. The proteins that comprise this system of protein kinases, phospho-binding targets and phosphatases are typically modular in organization, in the sense that they are composed of multiple globular domains and smaller peptide motifs with binding or catalytic properties. The linkage of these binding and catalytic modules in new ways through genetic recombination, and the selection of particular domain combinations, has promoted the evolution of novel, biologically useful processes. Conversely, the joining of domains in aberrant combinations can subvert cell signalling and be causative in diseases such as cancer. Major inventions such as phosphotyrosine (pTyr)-mediated signalling that flourished in the first multi-cellular animals and their immediate predecessors resulted from stepwise evolutionary progression. This involved changes in the binding properties of interaction domains such as SH2 and their linkage to new domain types, and alterations in the catalytic specificities of kinases and phosphatases. This review will focus on the modular aspects of signalling networks and the mechanism by which they may have evolved. PMID:22889906

  10. Fluorescent ampicillin analogues as multifunctional disguising agents against opsonization

    NASA Astrophysics Data System (ADS)

    Kotagiri, Nalinikanth; Sakon, Joshua; Han, Haewook; Zharov, Vladimir P.; Kim, Jin-Woo

    2016-06-01

    Cancer nanomedicines are opening new paradigms in cancer management and recent research points to how they can vastly improve imaging and therapy through multimodality and multifunctionality. However, challenges to achieving optimal efficacy are manifold starting from processing materials and evaluating their intended effectiveness on biological tissue, to developing new strategies aimed at improving transport of these materials through the biological milieu to the target tissue. Here, we report a fluorescent derivative of a beta-lactam antibiotic, ampicillin (termed iAmp) and its multifunctional physicobiochemical characteristics and potential as a biocompatible shielding agent and an effective dispersant. Carbon nanotubes (CNTs) were chosen to demonstrate the efficacy of iAmp. CNTs are known for their versatility and have been used extensively for cancer theranostics as photothermal and photoacoustic agents, but have limited solubility in water and biocompatibility. Traditional dispersants are associated with imaging artifacts and are not fully biocompatible. The chemical structure of iAmp is consistent with a deamination product of ampicillin. Although the four-membered lactam ring is intact, it does not retain the antibiotic properties. The iAmp is an effective dispersant and simultaneously serves as a fluorescent label for single-walled CNTs (SWNTs) with minimal photobleaching. The iAmp also enables bioconjugation of SWNTs to bio-ligands such as antibodies through functional carboxyl groups. Viability tests show that iAmp-coated SWNTs have minimal toxicity. Bio-stability tests under physiological conditions reveal that iAmp coating not only remains stable in a biologically relevant environment with high protein and salt concentrations, but also renders SWNTs transparent against nonspecific protein adsorption, also known as protein corona. Mammalian tissue culture studies with macrophages and opsonins validate that iAmp coating affords immunological resistance

  11. A modular BLSS simulation model

    NASA Technical Reports Server (NTRS)

    Rummel, John D.; Volk, Tyler

    1987-01-01

    A bioregenerative life support system (BLSS) for extraterrestrial use will be faced with coordination problems more acute than those in any ecosystem found on Earth. A related problem in BLSS design is providing an interface between the various life support processors, one that will allow for their coordination while still allowing for system expansion. A modular model is presented of a BLSS that interfaces system processors only with the material storage reservoirs, allowing those reservoirs to act as the principal buffers in the system and thus minimizing difficulties with processor coordination. The modular nature of the model allows independent development of the detailed submodels that exist within the model framework. Using this model, BLSS dynamics were investigated under normal conditions and under various failure modes. Partial and complete failures of various components, such as the waste processors or the plants themselves, drive transient responses in the model system, allowing the examination of the effectiveness of the system reservoirs as buffers. The results from simulations help to determine control strategies and BLSS design requirements. An evolved version could be used as an interactive control aid in a future BLSS.

  12. Learning modular policies for robotics.

    PubMed

    Neumann, Gerhard; Daniel, Christian; Paraschos, Alexandros; Kupcsik, Andras; Peters, Jan

    2014-01-01

    A promising idea for scaling robot learning to more complex tasks is to use elemental behaviors as building blocks to compose more complex behavior. Ideally, such building blocks are used in combination with a learning algorithm that is able to learn to select, adapt, sequence and co-activate the building blocks. While there has been a lot of work on approaches that support one of these requirements, no learning algorithm exists that unifies all these properties in one framework. In this paper we present our work on a unified approach for learning such a modular control architecture. We introduce new policy search algorithms that are based on information-theoretic principles and are able to learn to select, adapt and sequence the building blocks. Furthermore, we developed a new representation for the individual building block that supports co-activation and principled ways for adapting the movement. Finally, we summarize our experiments for learning modular control architectures in simulation and with real robots. PMID:24966830

  13. Compact stellarators with modular coils

    PubMed Central

    Garabedian, P. R.

    2000-01-01

    Compact stellarator designs with modular coils and only two or three field periods are now available; these designs have both good stability and quasiaxial symmetry providing adequate transport for a magnetic fusion reactor. If the bootstrap current assumes theoretically predicted values a three field period configuration is optimal, but if that net current turns out to be lower, a device with two periods and just 12 modular coils might be better. There are also attractive designs with quasihelical symmetry and four or five periods whose properties depend less on the bootstrap current. Good performance requires that there be a satisfactory magnetic well in the vacuum field, which is a property lacking in a stellarator-tokamak hybrid that has been proposed for a proof of principle experiment. In this paper, we present an analysis of stability for these configurations that is based on a mountain pass theorem asserting that, if two solutions of the problem of magnetohydrodynamic equilibrium can be found, then there has to be an unstable solution. We compare results of our theory of equilibrium, stability, and transport with recently announced measurements from the large LHD experiment in Japan. PMID:10899993

  14. MULTIFUNCTIONAL AND STIMULI-SENSITIVE PHARMACEUTICAL NANOCARRIERS

    PubMed Central

    Torchilin, Vladimir

    2011-01-01

    Currently used pharmaceutical nanocarriers, such as liposomes, micelles, and polymeric nanoparticles, demonstrate a broad variety of useful properties, such as longevity in the body; specific targeting to certain disease sites; enhanced intracellular penetration; contrast properties allowing for direct carrier visualization in vivo; stimili-sensitivity, and others. Some of those pharmaceutical carriers have already made their way into clinic, while others are still under preclinical development. In certain cases, the pharmaceutical nanocarriers combine several of the listed properties. Long-circulating immunoliposomes capable of prolonged residence in the blood and specific target recognition represent one of examples of this kind. The engineering of multifunctional pharmaceutical nanocarriers combining several useful properties in one particle can significantly enhance the efficacy of many therapeutic and diagnostic protocols. This paper considers the current status and possible future directions in the emerging area of multifunctional nanocarriers with primary attention on the combination of such properties as longevity, targetability, intracellular penetration, contrast loading, and stimuli sensitivity. PMID:18977297

  15. Teachers' Perceptions of Modular Technology Education Laboratories

    ERIC Educational Resources Information Center

    Harris, Kara S.

    2005-01-01

    The purpose of this study was to examine teachers' perceptions concerning the modular technology approach to teaching technology education in Georgia. The study addressed the following basic research question: What do teachers in Georgia perceive to be the main advantages and drawbacks to teaching technology education in a modular environment…

  16. The modular class of a Dirac map

    NASA Astrophysics Data System (ADS)

    Caseiro, Raquel

    2016-06-01

    In this paper we study the modular classes of Dirac manifolds and of Dirac maps, and we discuss their basic properties. We apply these results to explain the relationship between the modular classes of the various structures involved in the reduction of a Poisson manifold under the action of a Poisson-Lie group.

  17. Modular interdependency in complex dynamical systems.

    PubMed

    Watson, Richard A; Pollack, Jordan B

    2005-01-01

    Herbert A. Simon's characterization of modularity in dynamical systems describes subsystems as having dynamics that are approximately independent of those of other subsystems (in the short term). This fits with the general intuition that modules must, by definition, be approximately independent. In the evolution of complex systems, such modularity may enable subsystems to be modified and adapted independently of other subsystems, whereas in a nonmodular system, modifications to one part of the system may result in deleterious side effects elsewhere in the system. But this notion of modularity and its effect on evolvability is not well quantified and is rather simplistic. In particular, modularity need not imply that intermodule dependences are weak or unimportant. In dynamical systems this is acknowledged by Simon's suggestion that, in the long term, the dynamical behaviors of subsystems do interact with one another, albeit in an "aggregate" manner--but this kind of intermodule interaction is omitted in models of modularity for evolvability. In this brief discussion we seek to unify notions of modularity in dynamical systems with notions of how modularity affects evolvability. This leads to a quantifiable measure of modularity and a different understanding of its effect on evolvability. PMID:16197673

  18. Modular Construction: The Wave of the Future.

    ERIC Educational Resources Information Center

    Savage, Chuck

    1989-01-01

    Modular construction of school buildings offers speed of construction, with 100 percent contractor responsibility for the completed structures. Under negotiated terms, modular projects can be purchased outright or through long-term leasing arrangements that provide ownership at the end of the lease period. (MLF)

  19. Twisted Cyclic Cohomology and Modular Fredholm Modules

    NASA Astrophysics Data System (ADS)

    Rennie, Adam; Sitarz, Andrzej; Yamashita, Makoto

    2013-07-01

    Connes and Cuntz showed in [Comm. Math. Phys. 114 (1988), 515-526] that suitable cyclic cocycles can be represented as Chern characters of finitely summable semifinite Fredholm modules. We show an analogous result in twisted cyclic cohomology using Chern characters of modular Fredholm modules. We present examples of modular Fredholm modules arising from Podleś spheres and from SUq(2).

  20. Holmium laser for multifunctional use in urology

    NASA Astrophysics Data System (ADS)

    Watson, Graham M.; Shroff, Sunil; Thomas, Robert; Kellett, Michael

    1994-05-01

    The holmium laser pulsed at 350 microsecond cuts tissue and fragments calculi. It has been assessed for minimally invasive urological intervention. It is useful for partly excising and partly coagulating tumors, incising strictures and the obstructed PUJ. It partly drill and partly fragments urinary calculi however hard. Other lasers are more effective at any one particular application, but this laser is a useful compromise as a multifunctional device.

  1. Approach to multifunction radar tracker design

    NASA Astrophysics Data System (ADS)

    Casar Corredera, Jose R.; Harvey, Denis H.

    A new approach is presented to select optimally both the energy of the tracking waveforms and the track sampling rates which jointly minimize occupancy and satisfy angular accuracy requirements for a multifunction radar. The design process is illustrated for a particular system. The results suggest that the radar's energy should be managed as a function of target size and range so as to obtain an SNR as close as possible to its optimal value.

  2. Multiscale/Multifunctional Probabilistic Composite Fatigue

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.

    2010-01-01

    A multilevel (multiscale/multifunctional) evaluation is demonstrated by applying it to three different sample problems. These problems include the probabilistic evaluation of a space shuttle main engine blade, an engine rotor and an aircraft wing. The results demonstrate that the blade will fail at the highest probability path, the engine two-stage rotor will fail by fracture at the rim and the aircraft wing will fail at 109 fatigue cycles with a probability of 0.9967.

  3. A Multifunctional Coating for Autonomous Corrosion Control

    NASA Technical Reports Server (NTRS)

    Calle, Luz M.; Li, Wenyan; Buhrow, Jerry W.; Jolley, Scott t.

    2011-01-01

    Nearly all metals and their alloys are subject to corrosion that causes them to lose their structural integrity or other critical functionality. Protective coatings are the most commonly used method of corrosion control. However, progressively stricter environmental regulations have resulted in the ban of many commercially available corrosion protective coatings due to the harmful effects of their solvents or corrosion inhibitors. This work concerns the development of a multifunctional smart coating for the autonomous control of corrosion. This coating is being developed to have the inherent ability to detect the chemical changes associated with the onset of corrosion and respond autonomously to indicate it and control it. The multi-functionality of the coating is based on microencapsulation technology specifically designed for corrosion control applications. This design has, in addition to all the advantages of existing microcapsulation designs, the corrosion controlled release function that triggers the delivery of corrosion indicators and inhibitors on demand, only when and where needed. Microencapsulation of self-healing agents for autonomous repair of mechanical damage to the coating is also being pursued. Corrosion indicators, corrosion inhibitors, as well as self-healing agents, have been encapsulated and dispersed into several paint systems to test the corrosion detection, inhibition, and self-healing properties of the coating. Key words: Corrosion, coating, autonomous corrosion control, corrosion indication, corrosion inhibition, self-healing coating, smart coating, multifunctional coating, microencapsulation.

  4. Biomimetic multifunctional surfaces inspired from animals.

    PubMed

    Han, Zhiwu; Mu, Zhengzhi; Yin, Wei; Li, Wen; Niu, Shichao; Zhang, Junqiu; Ren, Luquan

    2016-08-01

    Over millions of years, animals have evolved to a higher intelligent level for their environment. A large number of diverse surface structures on their bodies have been formed to adapt to the extremely harsh environment. Just like the structural diversity existed in plants, the same also applies true in animals. Firstly, this article provides an overview and discussion of the most common functional surface structures inspired from animals, such as drag reduction, noise reduction, anti-adhesion, anti-wear, anti-erosion, anti-fog, water capture, and optical surfaces. Then, some typical characteristics of morphologies, structures, and materials of the animal multifunctional surfaces were discussed. The adaptation of these surfaces to environmental conditions was also analyzed. It mainly focuses on the relationship between their surface functions and their surface structural characteristics. Afterwards, the multifunctional mechanisms or principles of these surfaces were discussed. Models of these structures were provided for the development of structure materials and machinery surfaces. At last, fabrication techniques and existing or potential technical applications inspired from biomimetic multifunctional surfaces in animals were also discussed. The application prospects of the biomimetic functional surfaces are very broad, such as civil field of self-cleaning textile fabrics and non-stick pots, ocean field of oil-water separation, sports field of swimming suits, space development field of lens arrays. PMID:27085632

  5. Small Modular Reactors: Institutional Assessment

    SciTech Connect

    Joseph Perkowski, Ph.D.

    2012-06-01

    ? Objectives include, among others, a description of the basic development status of “small modular reactors” (SMRs) focused primarily on domestic activity; investigation of the domestic market appeal of modular reactors from the viewpoints of both key energy sector customers and also key stakeholders in the financial community; and consideration of how to proceed further with a pro-active "core group" of stakeholders substantially interested in modular nuclear deployment in order to provide the basis to expedite design/construction activity and regulatory approval. ? Information gathering was via available resources, both published and personal communications with key individual stakeholders; published information is limited to that already in public domain (no confidentiality); viewpoints from interviews are incorporated within. Discussions at both government-hosted and private-hosted SMR meetings are reflected herein. INL itself maintains a neutral view on all issues described. Note: as per prior discussion between INL and CAP, individual and highly knowledgeable senior-level stakeholders provided the bulk of insights herein, and the results of those interviews are the main source of the observations of this report. ? Attachment A is the list of individual stakeholders consulted to date, including some who provided significant earlier assessments of SMR institutional feasibility. ? Attachments B, C, and D are included to provide substantial context on the international status of SMR development; they are not intended to be comprehensive and are individualized due to the separate nature of the source materials. Attachment E is a summary of the DOE requirements for winning teams regarding the current SMR solicitation. Attachment F deserves separate consideration due to the relative maturity of the SMART SMR program underway in Korea. Attachment G provides illustrative SMR design features and is intended for background. Attachment H is included for overview

  6. Modular Homogeneous Chromophore-Catalyst Assemblies.

    PubMed

    Mulfort, Karen L; Utschig, Lisa M

    2016-05-17

    Photosynthetic reaction center (RC) proteins convert incident solar energy to chemical energy through a network of molecular cofactors which have been evolutionarily tuned to couple efficient light-harvesting, directional electron transfer, and long-lived charge separation with secondary reaction sequences. These molecular cofactors are embedded within a complex protein environment which precisely positions each cofactor in optimal geometries along efficient electron transfer pathways with localized protein environments facilitating sequential and accumulative charge transfer. By contrast, it is difficult to approach a similar level of structural complexity in synthetic architectures for solar energy conversion. However, by using appropriate self-assembly strategies, we anticipate that molecular modules, which are independently synthesized and optimized for either light-harvesting or redox catalysis, can be organized into spatial arrangements that functionally mimic natural photosynthesis. In this Account, we describe a modular approach to new structural designs for artificial photosynthesis which is largely inspired by photosynthetic RC proteins. We focus on recent work from our lab which uses molecular modules for light-harvesting or proton reduction catalysis in different coordination geometries and different platforms, spanning from discrete supramolecular assemblies to molecule-nanoparticle hybrids to protein-based biohybrids. Molecular modules are particularly amenable to high-resolution characterization of the ground and excited state of each module using a variety of physical techniques; such spectroscopic interrogation helps our understanding of primary artificial photosynthetic mechanisms. In particular, we discuss the use of transient optical spectroscopy, EPR, and X-ray scattering techniques to elucidate dynamic structural behavior and light-induced kinetics and the impact on photocatalytic mechanism. Two different coordination geometries of

  7. ASMPKS: an analysis system for modular polyketide synthases

    PubMed Central

    Tae, Hongseok; Kong, Eun-Bae; Park, Kiejung

    2007-01-01

    Background Polyketides are secondary metabolites of microorganisms with diverse biological activities, including pharmacological functions such as antibiotic, antitumor and agrochemical properties. Polyketides are synthesized by serialized reactions of a set of enzymes called polyketide synthase(PKS)s, which coordinate the elongation of carbon skeletons by the stepwise condensation of short carbon precursors. Due to their importance as drugs, the volume of data on polyketides is rapidly increasing and creating a need for computational analysis methods for efficient polyketide research. Moreover, the increasing use of genetic engineering to research new kinds of polyketides requires genome wide analysis. Results We describe a system named ASMPKS (Analysis System for Modular Polyketide Synthesis) for computational analysis of PKSs against genome sequences. It also provides overall management of information on modular PKS, including polyketide database construction, new PKS assembly, and chain visualization. ASMPKS operates on a web interface to construct the database and to analyze PKSs, allowing polyketide researchers to add their data to this database and to use it easily. In addition, the ASMPKS can predict functional modules for a protein sequence submitted by users, estimate the chemical composition of a polyketide synthesized from the modules, and display the carbon chain structure on the web interface. Conclusion ASMPKS has powerful computation features to aid modular PKS research. As various factors, such as starter units and post-processing, are related to polyketide biosynthesis, ASMPKS will be improved through further development for study of the factors. PMID:17764579

  8. BESST: A Miniature, Modular Radiometer

    NASA Technical Reports Server (NTRS)

    Warden, Robert; Good, William; Baldwin-Stevens, Erik

    2010-01-01

    A new radiometer assembly has been developed that incorporates modular design principles in order to provide flexibility and versatility. The assembly, shown in Figure 1, is made up of six modules plus a central cubical frame. A small thermal imaging detector is used to determine the temperature of remote objects. To improve the accuracy of the temperature reading, frequent calibration is required. The detector must view known temperature targets before viewing the remote object. Calibration is achieved by using a motorized fold mirror to select the desired scene the detector views. The motor steps the fold mirror through several positions, which allows the detector to view the calibration targets or the remote object. The details, features, and benefits of the radiometer are described in this paper.

  9. Osmotrophy in modular Ediacara organisms

    PubMed Central

    Laflamme, Marc; Xiao, Shuhai; Kowalewski, Michał

    2009-01-01

    The Ediacara biota include macroscopic, morphologically complex soft-bodied organisms that appear globally in the late Ediacaran Period (575–542 Ma). The physiology, feeding strategies, and functional morphology of the modular Ediacara organisms (rangeomorphs and erniettomorphs) remain debated but are critical for understanding their ecology and phylogeny. Their modular construction triggered numerous hypotheses concerning their likely feeding strategies, ranging from micro-to-macrophagus feeding to photoautotrophy to osmotrophy. Macrophagus feeding in rangeomorphs and erniettomorphs is inconsistent with their lack of oral openings, and photoautotrophy in rangeomorphs is contradicted by their habitats below the photic zone. Here, we combine theoretical models and empirical data to evaluate the feasibility of osmotrophy, which requires high surface area to volume (SA/V) ratios, as a primary feeding strategy of rangeomorphs and erniettomorphs. Although exclusively osmotrophic feeding in modern ecosystems is restricted to microscopic bacteria, this study suggests that (i) fractal branching of rangeomorph modules resulted in SA/V ratios comparable to those observed in modern osmotrophic bacteria, and (ii) rangeomorphs, and particularly erniettomorphs, could have achieved osmotrophic SA/V ratios similar to bacteria, provided their bodies included metabolically inert material. Thus, specific morphological adaptations observed in rangeomorphs and erniettomorphs may have represented strategies for overcoming physiological constraints that typically make osmotrophy prohibitive for macroscopic life forms. These results support the viability of osmotrophic feeding in rangeomorphs and erniettomorphs, help explain their taphonomic peculiarities, and point to the possible importance of earliest macroorganisms for cycling dissolved organic carbon that may have been present in abundance during Ediacaran times. PMID:19706530

  10. MODULAR MANIPULATOR FOR ROBOTICS APPLICATIONS

    SciTech Connect

    Joseph W. Geisinger, Ph.D.

    2001-07-31

    ARM Automation, Inc. is developing a framework of modular actuators that can address the DOE's wide range of robotics needs. The objective of this effort is to demonstrate the effectiveness of this technology by constructing a manipulator from these actuators within a glovebox for Automated Plutonium Processing (APP). At the end of the project, the system of actuators was used to construct several different manipulator configurations, which accommodate common glovebox tasks such as repackaging. The modular nature and quickconnects of this system simplify installation into ''hot'' boxes and any potential modifications or repair therein. This work focused on the development of self-contained robotic actuator modules including the embedded electronic controls for the purpose of building a manipulator system. Both of the actuators developed under this project contain the control electronics, sensors, motor, gear train, wiring, system communications and mechanical interfaces of a complete robotics servo device. Test actuators and accompanying DISC{trademark}s underwent validation testing at The University of Texas at Austin and ARM Automation, Inc. following final design and fabrication. The system also included custom links, an umbilical cord, an open architecture PC-based system controller, and operational software that permitted integration into a completely functional robotic manipulator system. The open architecture on which this system is based avoids proprietary interfaces and communication protocols which only serve to limit the capabilities and flexibility of automation equipment. The system was integrated and tested in the contractor's facility for intended performance and operations. The manipulator was tested using the full-scale equipment and process mock-ups. The project produced a practical and operational system including a quantitative evaluation of its performance and cost.

  11. Multifunctional role of β-1, 3 glucan binding protein purified from the haemocytes of blue swimmer crab Portunus pelagicus and in vitro antibacterial activity of its reaction product.

    PubMed

    Anjugam, Mahalingam; Iswarya, Arokiadhas; Vaseeharan, Baskaralingam

    2016-01-01

    β-1, 3 glucan binding protein (β-GBP) was isolated from the haemocytes of blue swimmer crab, Portunus pelagicus and purified by laminarin coupled Sephadex G-100 affinity column chromatography. The purified β-GBP has the molecular mass of 100 kDa, confirmed by SDS-PAGE. The X-ray diffraction analysis of purified β-GBP indicates the crystalline nature of the protein and also the presence of single peak confirming the existence of β-glucan molecule. The results of agglutination assay showed that the purified β-GBP had the ability to agglutinate with yeast cell, Saccharomyces cerevisiae and mammalian erythrocytes. β-GBP can agglutinate with yeast cells at the concentration of 50 μg/ml. The phagocytic and encapsulation activity of purified β-GBP from P. pelagicus was determined with yeast cell S. cerevisiae and sepharose bead suspension respectively. This reveals that, β-GBP have the ability to detect the pathogen associated molecular patterns (PAMP) found on the surface of fungi and bacteria. The recognition of invading foreign substances and in the involvement of functional activities induces the activation of prophenoloxidase. This revealed that β-GBP play a major role in the innate immune system of crustaceans by stimulating the prophenoloxidase system. Moreover, it was obvious to note that β-GBP reaction product exhibited antibacterial and antibiofilm activity against Gram positive and Gram negative bacteria. This study concludes the functional aspects of β-GBP purified from P. pelagicus and its vital role in the stimulation of prophenoloxidase cascade during the pathogenic infection. PMID:26611720

  12. Intron-exon organization of the gene for the multifunctional animal fatty acid synthase.

    PubMed Central

    Amy, C M; Williams-Ahlf, B; Naggert, J; Smith, S

    1992-01-01

    The complete intron-exon organization of the gene encoding a multifunctional mammalian fatty acid synthase has been elucidated, and specific exons have been assigned to coding sequences for the component domains of the protein. The rat gene is interrupted by 42 introns and the sequences bordering the splice-site junctions universally follow the GT/AG rule. However, of the 41 introns that interrupt the coding region of the gene, 23 split the reading frame in phase I, 14 split the reading frame in phase 0, and only 4 split the reading frame in phase II. Remarkably, 46% of the introns interrupt codons for glycine. With only one exception, boundaries between the constituent enzymes of the multifunctional polypeptide coincide with the location of introns in the gene. The significance of the predominance of phase I introns, the almost uniformly short length of the 42 introns and the overall small size of the gene, is discussed in relation to the evolution of multifunctional proteins. Images PMID:1736293

  13. Identification of Multi-Functional Enzyme with Multi-Label Classifier

    PubMed Central

    Che, Yuxin; Ju, Ying; Xuan, Ping; Long, Ren; Xing, Fei

    2016-01-01

    Enzymes are important and effective biological catalyst proteins participating in almost all active cell processes. Identification of multi-functional enzymes is essential in understanding the function of enzymes. Machine learning methods perform better in protein structure and function prediction than traditional biological wet experiments. Thus, in this study, we explore an efficient and effective machine learning method to categorize enzymes according to their function. Multi-functional enzymes are predicted with a special machine learning strategy, namely, multi-label classifier. Sequence features are extracted from a position-specific scoring matrix with autocross-covariance transformation. Experiment results show that the proposed method obtains an accuracy rate of 94.1% in classifying six main functional classes through five cross-validation tests and outperforms state-of-the-art methods. In addition, 91.25% accuracy is achieved in multi-functional enzyme prediction, which is often ignored in other enzyme function prediction studies. The online prediction server and datasets can be accessed from the link http://server.malab.cn/MEC/. PMID:27078147

  14. Size reduction of complex networks preserving modularity

    SciTech Connect

    Arenas, A.; Duch, J.; Fernandez, A.; Gomez, S.

    2008-12-24

    The ubiquity of modular structure in real-world complex networks is being the focus of attention in many trials to understand the interplay between network topology and functionality. The best approaches to the identification of modular structure are based on the optimization of a quality function known as modularity. However this optimization is a hard task provided that the computational complexity of the problem is in the NP-hard class. Here we propose an exact method for reducing the size of weighted (directed and undirected) complex networks while maintaining invariant its modularity. This size reduction allows the heuristic algorithms that optimize modularity for a better exploration of the modularity landscape. We compare the modularity obtained in several real complex-networks by using the Extremal Optimization algorithm, before and after the size reduction, showing the improvement obtained. We speculate that the proposed analytical size reduction could be extended to an exact coarse graining of the network in the scope of real-space renormalization.

  15. A Modular Approach to Redundant Robot Control

    SciTech Connect

    Anderson, R.J.

    1997-12-01

    This paper describes a modular approach for computing redundant robot kinematics. First some conventional redundant control methods are presented and shown to be `passive control laws`, i.e. they can be represented by a network consisting of passive elements. These networks are then put into modular form by applying scattering operator techniques. Additional subnetwork modules can then be added to further shape the motion. Modules for obstacle detection, joint limit avoidance, proximity sensing, and for imposing nonlinear velocity constraints are presented. The resulting redundant robot control system is modular, flexible and robust.

  16. Modular standards for emerging avionics technologies

    NASA Astrophysics Data System (ADS)

    Radcliffe, B.; Boaz, J.

    The present investigation is concerned with modular standards for the integration of new avionics technologies into production aircraft, taking into account also major retrofit programs. It is pointed out that avionics systems are about to undergo drastic changes in the partitioning of functions and judicious sharing of resources. These changes have the potential to significantly improve reliability and maintainability, and to reduce costs. Attention is given to a definition of the modular avionics concept, the existing module program, the development approach, development progress on the modular avionics standard, and the future of avionics installation standards.

  17. Modular Buildings: A Quick, Quality Solution for Schools.

    ERIC Educational Resources Information Center

    School Planning & Management, 2001

    2001-01-01

    Highlights the history of the modular classroom industry and emergence of the Modular Building Institute. Analyzes the differences between temporary portable classrooms and permanent modular additions. Also examines the possible influence of modular classrooms on future facility design and the ways that educational facilities officials are saving…

  18. Modular optimization code package: MOZAIK

    NASA Astrophysics Data System (ADS)

    Bekar, Kursat B.

    This dissertation addresses the development of a modular optimization code package, MOZAIK, for geometric shape optimization problems in nuclear engineering applications. MOZAIK's first mission, determining the optimal shape of the D2O moderator tank for the current and new beam tube configurations for the Penn State Breazeale Reactor's (PSBR) beam port facility, is used to demonstrate its capabilities and test its performance. MOZAIK was designed as a modular optimization sequence including three primary independent modules: the initializer, the physics and the optimizer, each having a specific task. By using fixed interface blocks among the modules, the code attains its two most important characteristics: generic form and modularity. The benefit of this modular structure is that the contents of the modules can be switched depending on the requirements of accuracy, computational efficiency, or compatibility with the other modules. Oak Ridge National Laboratory's discrete ordinates transport code TORT was selected as the transport solver in the physics module of MOZAIK, and two different optimizers, Min-max and Genetic Algorithms (GA), were implemented in the optimizer module of the code package. A distributed memory parallelism was also applied to MOZAIK via MPI (Message Passing Interface) to execute the physics module concurrently on a number of processors for various states in the same search. Moreover, dynamic scheduling was enabled to enhance load balance among the processors while running MOZAIK's physics module thus improving the parallel speedup and efficiency. In this way, the total computation time consumed by the physics module is reduced by a factor close to M, where M is the number of processors. This capability also encourages the use of MOZAIK for shape optimization problems in nuclear applications because many traditional codes related to radiation transport do not have parallel execution capability. A set of computational models based on the

  19. Fluorescent ampicillin analogues as multifunctional disguising agents against opsonization.

    PubMed

    Kotagiri, Nalinikanth; Sakon, Joshua; Han, Haewook; Zharov, Vladimir P; Kim, Jin-Woo

    2016-07-01

    Cancer nanomedicines are opening new paradigms in cancer management and recent research points to how they can vastly improve imaging and therapy through multimodality and multifunctionality. However, challenges to achieving optimal efficacy are manifold starting from processing materials and evaluating their intended effectiveness on biological tissue, to developing new strategies aimed at improving transport of these materials through the biological milieu to the target tissue. Here, we report a fluorescent derivative of a beta-lactam antibiotic, ampicillin (termed iAmp) and its multifunctional physicobiochemical characteristics and potential as a biocompatible shielding agent and an effective dispersant. Carbon nanotubes (CNTs) were chosen to demonstrate the efficacy of iAmp. CNTs are known for their versatility and have been used extensively for cancer theranostics as photothermal and photoacoustic agents, but have limited solubility in water and biocompatibility. Traditional dispersants are associated with imaging artifacts and are not fully biocompatible. The chemical structure of iAmp is consistent with a deamination product of ampicillin. Although the four-membered lactam ring is intact, it does not retain the antibiotic properties. The iAmp is an effective dispersant and simultaneously serves as a fluorescent label for single-walled CNTs (SWNTs) with minimal photobleaching. The iAmp also enables bioconjugation of SWNTs to bio-ligands such as antibodies through functional carboxyl groups. Viability tests show that iAmp-coated SWNTs have minimal toxicity. Bio-stability tests under physiological conditions reveal that iAmp coating not only remains stable in a biologically relevant environment with high protein and salt concentrations, but also renders SWNTs transparent against nonspecific protein adsorption, also known as protein corona. Mammalian tissue culture studies with macrophages and opsonins validate that iAmp coating affords immunological resistance

  20. Development of thermoplastic coated multifunctional transmission elements

    NASA Astrophysics Data System (ADS)

    Golaz, B.; Michaud, V.; de Oliveira, R.; Månson, J.-A. E.

    2012-04-01

    We report on key challenges of the development of steel cords reinforced thermoplastic elastomer composites with smart functionalities: adhesion tailoring for a durable mechanical load transfer through steel cords or other transmission elements by the use of surface treatments and primers, and integrated distributed temperature and strain sensing by the use of embedded fiber optic sensors. Traditional surface treatments including silane coupling agent were outperformed in processing time, adhesion and durability by a fast-curing coupling method using a UV-curable primer; and the integrated distributed temperature and strain sensing capability was demonstrated. The practical applications of the resulting multifunctional transmission element are then discussed in light of these results.

  1. Ultrastrong, Stiff and Multifunctional Carbon Nanotube Composites

    SciTech Connect

    Wang, Xin; Yong, Zhenzhong; Li, Qingwen; Bradford, Philip D.; Liu, Wei; Tucker, Dennis S.; Cai, Wei; Wang, Hsin; Yuan, Fuh-Gwo; Zhu, Yuntian

    2012-01-01

    Carbon nanotubes (CNTs) are an order of magnitude stronger than any current engineering fiber. However, for the past two decades it has been a challenge to utilize their reinforcement potential in composites. Here we report CNT composites with unprecedented multifunctionalities, including record high strength (3.8 GPa), Young s modulus (293 GPa), electrical conductivity (1230 S cm-1) and thermal conductivity (41 W m-1 K-1). These superior properties are derived from the long length, high volume fraction, good alignment and reduced waviness of the CNTs, which were produced by a novel processing approach that can be easily scaled up for industrial production.

  2. Multifunctional epitaxial systems on silicon substrates

    NASA Astrophysics Data System (ADS)

    Singamaneni, Srinivasa Rao; Prater, John Thomas; Narayan, Jagdish

    2016-09-01

    Multifunctional heterostructures can exhibit a wide range of functional properties, including colossal magneto-resistance, magnetocaloric, and multiferroic behavior, and can display interesting physical phenomena including spin and charge ordering and strong spin-orbit coupling. However, putting this functionality to work remains a challenge. To date, most of the work reported in the literature has dealt with heterostructures deposited onto closely lattice matched insulating substrates such as DyScO3, SrTiO3 (STO), or STO buffered Si(100) using concepts of lattice matching epitaxy (LME). However, strain in heterostructures grown by LME is typically not fully relaxed and the layers contain detrimental defects such as threading dislocations that can significantly degrade the physical properties of the films and adversely affect the device characteristics. In addition, most of the substrates are incompatible with existing CMOS-based technology, where Si (100) substrates dominate. This review discusses recent advances in the integration of multifunctional oxide and non-oxide materials onto silicon substrates. An alternative thin film growth approach, called "domain matching epitaxy," is presented which identifies approaches for minimizing lattice strain and unwanted defects in large misfit systems (7%-25% and higher). This approach broadly allows for the integration of multifunctional materials onto silicon substrates, such that sensing, computation, and response functions can be combined to produce next generation "smart" devices. In general, pulsed laser deposition has been used to epitaxially grow these materials, although the concepts developed here can be extended to other deposition techniques, as well. It will be shown that TiN and yttria-stabilized zirconia template layers provide promising platforms for the integration of new functionality into silicon-based computer chips. This review paper reports on a number of thin-film heterostructure systems that span a

  3. 5-GHz fully differential multifunctional circuit

    NASA Astrophysics Data System (ADS)

    Plessas, F.; Tsitouras, A.; Kalivas, G.

    2012-09-01

    This letter presents a multifunctional circuit realising the functions of oscillation, frequency multiplication and frequency division at 5-GHz. A theoretical and experimental description of the circuit is given. The injection signal, which is used to stabilise the oscillation, is at a sub- or super-harmonic of the oscillation frequency having a power level as low as -30 dBm. Calculations and measurements of the phase noise are reported which indicate a phase noise improvement. The implementation of the circuit exhibits a phase noise of -110 dBc/Hz at 100 KHz offset whereas the improvement depends on the relative noise of the injected signal.

  4. Multifunctional hybrid nanogels for theranostic applications.

    PubMed

    Sierra-Martin, B; Fernandez-Barbero, A

    2015-11-14

    This paper reviews a wide set of theranostic applications based on the special properties associated with composite nanogels. The nanogels presented here are mostly hybridized with quantum dots, magnetic nanoparticles, and plasmonic metal noble nanoparticles. These inorganic components confer nanogels multifunctional properties that extend their applications from drug delivery systems to diagnosis and therapy. Nanogels can also be surface functionalized with specific ligands to achieve targeted therapy and reduce toxicity. This versatility makes hybrid nanogels very promising agents for imaging, diagnosis and treatment of cancer and other diseases. PMID:26371991

  5. Requirements for a multifunctional code architecture

    SciTech Connect

    Tiihonen, O.; Juslin, K.

    1997-07-01

    The present paper studies a set of requirements for a multifunctional simulation software architecture in the light of experiences gained in developing and using the APROS simulation environment. The huge steps taken in the development of computer hardware and software during the last ten years are changing the status of the traditional nuclear safety analysis software. The affordable computing power on the safety analysts table by far exceeds the possibilities offered to him/her ten years ago. At the same time the features of everyday office software tend to set standards to the way the input data and calculational results are managed.

  6. Cell-Targeting Cationic Gene Delivery System Based on a Modular Design Rationale.

    PubMed

    Liu, Jia; Xu, Luming; Jin, Yang; Qi, Chao; Li, Qilin; Zhang, Yunti; Jiang, Xulin; Wang, Guobin; Wang, Zheng; Wang, Lin

    2016-06-01

    En route to target cells, a gene carrier faces multiple extra- and intracellular hurdles that would affect delivery efficacy. Although diverse strategies have been proposed to functionalize gene carriers for individually overcoming these barriers, it is challenging to generate a single multifunctional gene carrier capable of surmounting all these barriers. Aiming at this challenge, we have developed a supramolecular modular approach to fabricate a multifunctional cationic gene delivery system. It consists of two prefunctionalized modules: (1) a host module: a polymer (PCD-SS-PDMAEMA) composed of poly(β-cyclodextrin) backbone and disulfide-linked PDMAEMA arms, expectedly acting to compact DNA and release DNA upon cleavage of disulfide linkers in reductive microenvironment; and (2) a guest module: adamantyl and folate terminated PEG (Ad-PEG-FA), expectedly functioning to reduce nonspecific interactions, improve biocompatibility, and provide folate-mediated cellular targeting specificity. Through the host-guest interaction between β-cyclodextrin units of the "host" module and adamantyl groups of the "guest" module, the PCD-SS-PDMAEMA-1 (host) and Ad-PEG-FA (guest) self-assemble forming a supramolecular pseudocopolymer (PCD-SS-PDMAEMA-1/PEG-FA). Our comprehensive analyses demonstrate that the functions preassigned to the two building modules are well realized. The gene carrier effectively compacts DNA into stable nanosized polyplexes resistant to enzymatic digestion, triggers DNA release in reducing environment, possesses significantly improved hemocompatibility, and specifically targets folate-receptor positive cells. Most importantly, endowed with these predesigned functions, the PCD-SS-PDMAEMA-1/PEG-FA supramolecular gene carrier exhibits excellent transfection efficacy for both pDNA and siRNA. Thus, this work represents a proof-of-concept example showing the efficiency and convenience of an adaptable, modular approach for conferring multiple functions to a single

  7. Crystallization and preliminary X-ray diffraction studies of FHA domains of Dun1 and Rad53 protein kinases.

    PubMed

    Blanchard, H; Fontes, M R; Hammet, A; Pike, B L; Teh, T; Gleichmann, T; Gooley, P R; Kobe, B; Heierhorst, J

    2001-03-01

    Forkhead-associated (FHA) domains are modular protein-protein interaction domains of approximately 130 amino acids present in numerous signalling proteins. FHA-domain-dependent protein interactions are regulated by phosphorylation of target proteins and FHA domains may be multifunctional phosphopeptide-recognition modules. FHA domains of the budding yeast cell-cycle checkpoint protein kinases Dun1p and Rad53p have been crystallized. Crystals of the Dun1-FHA domain exhibit the symmetry of the space group P6(1)22 or P6(5)22, with unit-cell parameters a = b = 127.3, c = 386.3 A; diffraction data have been collected to 3.1 A resolution on a synchrotron source. Crystals of the N-terminal FHA domain (FHA1) of Rad53p diffract to 4.0 A resolution on a laboratory X-ray source and have Laue-group symmetry 4/mmm, with unit-cell parameters a = b = 61.7, c = 104.3 A. PMID:11223532

  8. Modular biowaste monitoring system conceptual design

    NASA Technical Reports Server (NTRS)

    Fogal, G. L.

    1974-01-01

    The objective of the study was to define requirements and generate a conceptual design for a Modular Biowaste Monitoring System for specifically supporting shuttle life science experimental and diagnostic programs.

  9. Modular digital holographic fringe data processing system

    NASA Technical Reports Server (NTRS)

    Downward, J. G.; Vavra, P. C.; Schebor, F. S.; Vest, C. M.

    1985-01-01

    A software architecture suitable for reducing holographic fringe data into useful engineering data is developed and tested. The results, along with a detailed description of the proposed architecture for a Modular Digital Fringe Analysis System, are presented.

  10. Modular, Intelligent Power Systems for Space Exploration

    NASA Technical Reports Server (NTRS)

    Button, Robert

    2006-01-01

    NASA's new Space Exploration Initiative demands that vehicles, habitats, and rovers achieve unprecedented levels of reliability, safety, effectiveness, and affordability. Modular and intelligent electrical power systems are critical to achieving those goals. Modular electrical power systems naturally increase reliability and safety through built-in fault tolerance. These modular systems also enable standardization across a multitude of systems, thereby greatly increasing affordability of the programs. Various technologies being developed to support this new paradigm for space power systems will be presented. Examples include the use of digital control in power electronics to enable better performance and advanced modularity functions such as distributed, master-less control and series input power conversion. Also, digital control and robust communication enables new levels of power system control, stability, fault detection, and health management. Summary results from recent development efforts are presented along with expected future technology development needs required to support NASA's ambitious space exploration goals.

  11. Modular Solar Electric Power (MSEP) Systems (Presentation)

    SciTech Connect

    Hassani, V.

    2000-06-18

    This presentation discusses the development and deployment of Modular Solar Electric Power (MSEP) systems, the feasibility of application of existing binary power cycles to solar trough technology, and identification of next action items.

  12. COMPONENT VERSION IN MODULAR TOTAL HIP REVISION

    PubMed Central

    Kopec, Michael A.; Pemberton, Aaron; Milbrandt, Joseph C.; Allan, Gordon

    2009-01-01

    Morphologic changes of the proximal femur make revision total hip arthroplasty challenging. Metaphyseal retroversion and diaphyseal varus are common in this scenario. Twenty-one total hip revisions using a modular femoral prosthesis were examined by obtaining three radiographs (A/P, surgical lateral, and true lateral of the femur) to assemble CAD models for determining the range of modular component positioning. An average of femoral neck anteversion was observed. Seventeen of 21 cases (81%) had retroverted metaphyseal segments (−23.2°+/−17.4°) and/or varus stems (−32.1°+/−13.0°). Neck anteversion averaged 21.4°(+/−10.0°). One of 21 cases (5%) resulted in component orientation similar to a non-modular prosthesis. Modular components provide options to accommodate proximal femoral remodeling not afforded by monobloc stems in total hip revision surgery. PMID:19742077

  13. 47 CFR 15.212 - Modular transmitters.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... modular transmitter must have their own shielding. The physical crystal and tuning capacitors may be... shielded. The physical crystal and tuning capacitors may be located external to the shielded radio...

  14. 47 CFR 15.212 - Modular transmitters.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... modular transmitter must have their own shielding. The physical crystal and tuning capacitors may be... shielded. The physical crystal and tuning capacitors may be located external to the shielded radio...

  15. 47 CFR 15.212 - Modular transmitters.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... modular transmitter must have their own shielding. The physical crystal and tuning capacitors may be... shielded. The physical crystal and tuning capacitors may be located external to the shielded radio...

  16. 47 CFR 15.212 - Modular transmitters.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... modular transmitter must have their own shielding. The physical crystal and tuning capacitors may be... shielded. The physical crystal and tuning capacitors may be located external to the shielded radio...

  17. 47 CFR 15.212 - Modular transmitters.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... modular transmitter must have their own shielding. The physical crystal and tuning capacitors may be... shielded. The physical crystal and tuning capacitors may be located external to the shielded radio...

  18. MDA-7/IL-24: Multifunctional Cancer Killing Cytokine

    PubMed Central

    Menezes, Mitchell E.; Bhatia, Shilpa; Bhoopathi, Praveen; Das, Swadesh K.; Emdad, Luni; Dasgupta, Santanu; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand

    2015-01-01

    First identified almost two decades ago as a novel gene differentially expressed in human melanoma cells induced to terminally differentiate, MDA-7/IL-24 has since shown great potential as an anti-cancer gene. MDA-7/IL24, a secreted protein of the IL-10 family, functions as a cytokine at normal physiological levels and is expressed in tissues of the immune system. At supra-physiological levels, MDA-7/IL-24 plays a prominent role in inhibiting tumor growth, invasion, metastasis and angiogenesis and was recently shown to target tumor stem/initiating cells for death. Much of the attention focused on MDA-7/IL-24 originated from the fact that it can selectively induce cell death in cancer cells without affecting normal cells. Thus, this gene originally shown to be associated with melanoma cell differentiation has now proven to be a multi-functional protein affecting a broad array of cancers. Moreover, MDA-7/IL-24 has proven efficacious in a Phase I/II clinical trial in humans with multiple advanced cancers. As research in the field progresses, we will unravel more of the functions of MDA-7/IL-24 and define novel ways to utilize MDA-7/IL-24 in the treatment of cancer. PMID:25001534

  19. Immuno-targeting the multifunctional CD38 using nanobody

    PubMed Central

    Li, Ting; Qi, Shali; Unger, Mandy; Hou, Yun Nan; Deng, Qi Wen; Liu, Jun; Lam, Connie M. C.; Wang, Xian Wang; Xin, Du; Zhang, Peng; Koch-Nolte, Friedrich; Hao, Quan; Zhang, Hongmin; Lee, Hon Cheung; Zhao, Yong Juan

    2016-01-01

    CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10−11 molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma. PMID:27251573

  20. Plant species richness and ecosystem multifunctionality in global drylands

    USGS Publications Warehouse

    Maestre, Fernando T.; Quero, Jose L.; Gotelli, Nicholas J.; Escudero, Adrian; Ochoa, Victoria; Delgado-Baquerizo, Manuel; Garcia-Gomez, Miguel; Bowker, Matthew A.; Soliveres, Santiago; Escolar, Cristina; Garcia-Palacios, Pablo; Berdugo, Miguel; Valencia, Enrique; Gozalo, Beatriz; Gallardo, Antonio; Aguilera, Lorgio; Arredondo, Tulio; Blones, Julio; Boeken, Bertrand; Bran, Donaldo; Conceicao, Abel A.; Cabrera, Omar; Chaieb, Mohamed; Derak, Mchich; Eldridge, David J.; Espinosa, Carlos I.; Florentino, Adriana; Gaitan, Juan; Gatica, M. Gabriel; Ghiloufi, Wahida; Gomez-Gonzalez, Susana; Gutie, Julio R.; Hernandez, Rosa M.; Huang, Xuewen; Huber-Sannwald, Elisabeth; Jankju, Mohammad; Miriti, Maria; Monerris, Jorge; Mau, Rebecca L.; Morici, Ernesto; Naseri, Kamal; Ospina, Abelardo; Polo, Vicente; Prina, Anibal; Pucheta, Eduardo; Ramirez-Collantes, David A.; Romao, Roberto; Tighe, Matthew; Torres-Diaz, Cristian; Val, James; Veiga, Jose P.; Wang, Deli; Zaady, Eli

    2012-01-01

    Experiments suggest that biodiversity enhances the ability of ecosystems to maintain multiple functions, such as carbon storage, productivity, and the buildup of nutrient pools (multifunctionality). However, the relationship between biodiversity and multifunctionality has never been assessed globally in natural ecosystems. We report here on a global empirical study relating plant species richness and abiotic factors to multifunctionality in drylands, which collectively cover 41% of Earth's land surface and support over 38% of the human population. Multifunctionality was positively and significantly related to species richness. The best-fitting models accounted for over 55% of the variation in multifunctionality and always included species richness as a predictor variable. Our results suggest that the preservation of plant biodiversity is crucial to buffer negative effects of climate change and desertification in drylands.

  1. Plant species richness and ecosystem multifunctionality in global drylands

    PubMed Central

    Maestre, Fernando T.; Quero, José L.; Gotelli, Nicholas J.; Escudero, Adriá; Ochoa, Victoria; Delgado-Baquerizo, Manuel; García-Gómez, Miguel; Bowker, Matthew A.; Soliveres, Santiago; Escolar, Cristina; García-Palacios, Pablo; Berdugo, Miguel; Valencia, Enrique; Gozalo, Beatriz; Gallardo, Antonio; Aguilera, Lorgio; Arredondo, Tulio; Blones, Julio; Boeken, Bertrand; Bran, Donaldo; Conceição, Abel A.; Cabrera, Omar; Chaieb, Mohamed; Derak, Mchich; Eldridge, David J.; Espinosa, Carlos I.; Florentino, Adriana; Gaitán, Juan; Gatica, M. Gabriel; Ghiloufi, Wahida; Gómez-González, Susana; Gutiérrez, Julio R.; Hernández, Rosa M.; Huang, Xuewen; Huber-Sannwald, Elisabeth; Jankju, Mohammad; Miriti, Maria; Monerris, Jorge; Mau, Rebecca L.; Morici, Ernesto; Naseri, Kamal; Ospina, Abelardo; Polo, Vicente; Prina, Aníbal; Pucheta, Eduardo; Ramírez-Collantes, David A.; Romão, Roberto; Tighe, Matthew; Torres-Díaz, Cristian; Val, James; Veiga, José P.; Wang, Deli; Zaady, Eli

    2013-01-01

    Experiments suggest that biodiversity enhances the ability of ecosystems to maintain multiple functions, such as carbon storage, productivity, and buildup of nutrient pools (multifunctionality). However, the relationship between biodiversity and multifunctionality has never been assessed globally in natural ecosystems. We report on the first global empirical study relating plant species richness and abiotic factors to multifunctionality in drylands, which collectively cover 41% of Earth’s land surface and support over 38% of the human population. Multifunctionality was positively and significantly related to species richness. The best-fitting models accounted for over 55% of the variation in multifunctionality, and always included species richness as a predictor variable. Our results suggest that preservation of plant biodiversity is crucial to buffer negative effects of climate change and desertification in drylands. PMID:22246775

  2. A 3-d modular gripper design tool

    SciTech Connect

    Brown, R.G.; Brost, R.C.

    1997-01-01

    Modular fixturing kits are precisely machined sets of components used for flexible, short-turnaround construction of fixtures for a variety of manufacturing purposes. A modular vise is a parallel-jaw vise, where each jaw is a modular fixture plate with a regular grid of precisely positioned holes. A modular vise can be used to locate and hold parts for machining, assembly, and inspection tasks. To fixture a part, one places pins in some of the holes so that when the vise is closed, the part is reliably located and completely constrained. The modular vise concept can be adapted easily to the design of modular parallel-jaw grippers for robots. By attaching a grid plate to each jaw of a parallel-jaw gripper, the authors gain the ability to easily construct high-quality grasps for a wide variety of parts from a standard set of hardware. Wallack and Canny developed a previous algorithm for planning planar grasp configurations for the modular vise. In this paper, the authors expand this work to produce a 3-d fixture/gripper design tool. They describe several analyses added to the planar algorithm to improve its utility, including a three-dimensional grasp quality metric based on geometric and force information, three-dimensional geometric loading analysis, and inter-gripper interference analysis to determine the compatibility of multiple grasps for handing the part from one gripper to another. Finally, the authors describe two applications which combine the utility of modular vise-style grasping with inter-gripper interference: The first is the design of a flexible part-handling subsystem for a part cleaning workcell under development at Sandia National Laboratories; the second is the automatic design of grippers that support the assembly of multiple products on a single assembly line.

  3. Optimal Network Modularity for Information Diffusion

    NASA Astrophysics Data System (ADS)

    Nematzadeh, Azadeh; Ferrara, Emilio; Flammini, Alessandro; Ahn, Yong-Yeol

    2014-08-01

    We investigate the impact of community structure on information diffusion with the linear threshold model. Our results demonstrate that modular structure may have counterintuitive effects on information diffusion when social reinforcement is present. We show that strong communities can facilitate global diffusion by enhancing local, intracommunity spreading. Using both analytic approaches and numerical simulations, we demonstrate the existence of an optimal network modularity, where global diffusion requires the minimal number of early adopters.

  4. Managing in an age of modularity.

    PubMed

    Baldwin, C Y; Clark, K B

    1997-01-01

    Modularity is a familiar principle in the computer industry. Different companies can independently design and produce components, suck as disk drives or operating software, and those modules will fit together into a complex and smoothly functioning product because the module makers obey a given set of design rules. Modularity in manufacturing is already common in many companies. But now a number of them are beginning to extend the approach into the design of their products and services. Modularity in design should tremendously boost the rate of innovation in many industries as it did in the computer industry. As businesses as diverse as auto manufacturing and financial services move toward modular designs, the authors say, competitive dynamics will change enormously. No longer will assemblers control the final product: suppliers of key modules will gain leverage and even take on responsibility for design rules. Companies will compete either by specifying the dominant design rules (as Microsoft does) or by producing excellent modules (as disk drive maker Quantum does). Leaders in a modular industry will control less, so they will have to watch the competitive environment closely for opportunities to link up with other module makers. They will also need to know more: engineering details that seemed trivial at the corporate level may now play a large part in strategic decisions. Leaders will also become knowledge managers internally because they will need to coordinate the efforts of development groups in order to keep them focused on the modular strategies the company is pursuing. PMID:10170333

  5. A 3-d modular gripper design tool

    SciTech Connect

    Brown, R.G.; Brost, R.C.

    1997-02-01

    Modular fixturing kits are sets of components used for flexible, rapid construction of fixtures. A modular vise is a parallel-jaw vise, each jaw of which is a modular fixture plate with a regular grid of precisely positioned holes. To fixture a part, one places pins in some of the holes so that when the vise is closed, the part is reliably located and completely constrained. The modular vise concept can be adapted easily to the design of modular parallel-jaw grippers for robots. By attaching a grid-plate to each jaw of a parallel-jaw gripper, one gains the ability to easily construct high-quality grasps for a wide variety of parts from a standard set of hardware. Wallack and Canny developed an algorithm for planning planar grasp configurations for the modular vise. In this paper, the authors expand this work to produce a 3-d fixture/gripper design tool. They describe several analyses they have added to the planar algorithm, including a 3-d grasp quality metric based on force information, 3-d geometric loading analysis, and inter-gripper interference analysis. Finally, the authors describe two applications of their code. One of these is an internal application at Sandia, while the other shows a potential use of the code for designing part of an agile assembly line.

  6. Modular Wideband Active Vibration Absorber

    NASA Technical Reports Server (NTRS)

    Smith, David R.; Zewari, Wahid; Lee, Kenneth Y.

    1999-01-01

    A comparison of space experiments with previous missions shows a common theme. Some of the recent experiments are based on the scientific fundamentals of instruments of prior years. However, the main distinguishing characteristic is the embodiment of advances in engineering and manufacturing in order to extract clearer and sharper images and extend the limits of measurement. One area of importance to future missions is providing vibration free observation platforms at acceptable costs. It has been shown by researchers that vibration problems cannot be eliminated by passive isolation techniques alone. Therefore, various organizations have conducted research in the area of combining active and passive vibration control techniques. The essence of this paper is to present progress in what is believed to be a new concept in this arena. It is based on the notion that if one active element in a vibration transmission path can provide a reasonable vibration attenuation, two active elements in series may provide more control options and better results. The paper presents the functions of a modular split shaft linear actuator developed by NASA's Goddard Space Flight Center and University of Massachusetts Lowell. It discusses some of the control possibilities facilitated by the device. Some preliminary findings and problems are also discussed.

  7. Test stations: a modular approach

    NASA Astrophysics Data System (ADS)

    Capone, Benjamin R.; Remillard, Paul; Everett, Jonathan E.

    1996-06-01

    Recent requests for test stations to characterize and evaluate thermal and visible imaging systems have shown remarkable similarities. They contain the usual request for target patterns for the measurement of MRTD, NETD, SiTF for the infrared thermal imager and similar patterns for measuring CTF and SNR for the visible imager. The combined systems almost invariably include some type of laser designator/rangefinder in the total package requiring the need for LOS registration among the various individual units. Similarities also exist in that the requests are for large collimator apertures and focal lengths for projecting the desired signals into the unit under test apertures. Diversified Optical Products, Inc. has developed and is continually improving test station hardware and software to provide modularity in design and versatility in operation while satisfying individual test requirements and maintaining low cost. A high emissivity, DSP controlled, high slew rate, low cost, blackbody source with excellent uniformity and stability has been produced to function as the driver for thermal image target projectors. Several types of sources for producing energy in the visible portion of the spectrum have been evaluated. Software for selection of targets, sources, focus and auto- collimation has been developed and tested.

  8. Faster Evolution of More Multifunctional Logic Circuits

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian; Zebulum, Ricardo

    2005-01-01

    A modification in a method of automated evolutionary synthesis of voltage-controlled multifunctional logic circuits makes it possible to synthesize more circuits in less time. Prior to the modification, the computations for synthesizing a four-function logic circuit by this method took about 10 hours. Using the method as modified, it is possible to synthesize a six-function circuit in less than half an hour. The concepts of automated evolutionary synthesis and voltage-controlled multifunctional logic circuits were described in a number of prior NASA Tech Briefs articles. To recapitulate: A circuit is designed to perform one of several different logic functions, depending on the value of an applied control voltage. The circuit design is synthesized following an automated evolutionary approach that is so named because it is modeled partly after the repetitive trial-and-error process of biological evolution. In this process, random populations of integer strings that encode electronic circuits play a role analogous to that of chromosomes. An evolved circuit is tested by computational simulation (prior to testing in real hardware to verify a final design). Then, in a fitness-evaluation step, responses of the circuit are compared with specifications of target responses and circuits are ranked according to how close they come to satisfying specifications. The results of the evaluation provide guidance for refining designs through further iteration.

  9. A Multifunctional Coating for Autonomous Corrosion Control

    NASA Technical Reports Server (NTRS)

    Calle, Luz M.; Hintze, Paul E.; Li, Wenyan; Buhrow, Jerry W.; Jolley, Scott T.

    2010-01-01

    Corrosion is a destructive process that often causes failure in metallic components and structures. Protective coatings are the most commonly used method of corrosion control. However, progressively stricter environmental regulations have resulted in the ban of many commercially available corrosion protective coatings due to the harmful effects of their solvents or corrosion inhibitors. This work concerns the development of a multifunctional, smart coating for the autonomous control of corrosion. This coating is being developed to have the inherent ability to detect the chemical changes associated with the onset of corrosion and respond autonomously to control it. The multi-functionality of the coating is based on microencapsulation technology specifically designed for corrosion control applications. This design has, in addition to all the advantages of other existing microcapsules designs, the corrosion controlled release function that allows the delivery of corrosion indicators and inhibitors on demand only when and where they are needed. Corrosion indicators as well as corrosion inhibitors have been incorporated into the microcapsules, blended into several paint systems, and tested for corrosion detection and protection efficacy.

  10. Multifunctional matrices for oral peptide delivery.

    PubMed

    Bernkop-Schnürch, A; Walker, G

    2001-01-01

    The oral administration of peptide drugs represents one of the greatest challenges in pharmaceutical technology. To gain a sufficient bioavailability of these therapeutic agents, various barriers including the mucus-layer barrier, the enzymatic barrier, and the membrane barrier have to be overcome. A promising strategy for achieving this goal is the use of multifunctional matrices. These matrices are based on polymers that display mucoadhesive properties, a permeation-enhancing effect, enzyme-inhibiting properties, and/or a high buffer capacity. Moreover, a sustained or delayed drug release can be provided by delivery systems that contain such polymers. Among them, polyacrylates, cellulose derivatives, and chitosan are promising excipients that can also be customized by chemical modification to improve certain properties. For example, the covalent attachment of thiol moieties on these polymers leads to improved mucoadhesive and permeation-enhancing properties, and the conjugation of enzyme inhibitors enables the matrices to provide protection for peptide drugs against enzymatic degradation. The efficacy of multifunctional matrices in oral peptide delivery has been verified by various in vivo studies that could pave the way for the development of commercially viable formulations. PMID:11763498

  11. Multifunctional landscapes--perspectives for the future.

    PubMed

    Brandt, Jesper

    2003-03-01

    New methods in landscape ecology to study the link between landscape heterogeneity and landscape functionality are needed. Heterogeneity is a basic characteristic of landscape, and landscape function is the capacity to change the structural heterogeneity of a landscape system. In most developed countries the industrialisation of agriculture has in general resulted in a change of agricultural landscapes from a small-grained heterogeneous pattern towards more monotonous and monofunctional landscapes. During the 1990's this trends seem to have changed due to a diversification of rural land use, and new trends in ubanisation. Whether these phases of landscape development should be expected in developing countries is a totally open question. Dealing with the study of multifunctionality of landscapes it is proposed to distinguish between ecological functionality of landscape ecosystems, functionality pertaining to land use and social functionality. Further, the relation between function, space and scale is important by the determination of spatial and time segregation as well as spatial and time integration of multifunctionality in landscapes. PMID:12765260

  12. Multifunction Habitat Workstation/OLED Development

    NASA Technical Reports Server (NTRS)

    Schumacher, Shawn; Salazar, George; Schmidt, Oron

    2013-01-01

    This paper gives a general outline of both a multifunction habitat workstation and the research put into an Organic Light Emitting Diode (OLED) device. It first covers the tests that the OLED device will go through to become flight ready along with reasoning. Guidelines for building an apparatus to house the display and its components are given next, with the build of such following. The three tests the OLED goes through are presented (EMI, Thermal/Vac, Radiation) along with the data recovered. The second project of a multifunction workstation is then discussed in the same pattern. Reasoning for building such a workstation with telepresence in mind is offered. Build guidelines are presented first, with the build timeline following. Building the workstation will then be shown in great detail along with accompanying photos. Once the workstation has been discussed, the versatility of its functions are given. The paper concludes with future views and concepts that can added when the time or technology presents itself.

  13. Designing multifunctional landscapes for forest conservation

    NASA Astrophysics Data System (ADS)

    Santika, Truly; Meijaard, Erik; Wilson, Kerrie A.

    2015-11-01

    A multifunctional landscape approach to forest protection has been advocated for tropical countries. Designing such landscapes necessitates that the role of different land uses in protecting forest be evaluated, along with the spatial interactions between land uses. However, such evaluations have been hindered by a lack of suitable analysis methodologies and data with fine spatial resolution over long time periods. We demonstrate the utility of a matching method with multiple categories to evaluate the role of alternative land uses in protecting forest. We also assessed the impact of land use change trajectories on the rate of deforestation. We employed data from Kalimantan (Indonesian Borneo) at three different time periods during 2000-2012 to illustrate our approach. Four single land uses (protected areas (PA), natural forest logging concessions (LC), timber plantation concessions (TC) and oil-palm plantation concessions (OC)) and two mixed land uses (mixed concessions and the overlap between concessions and PA) were assessed. The rate of deforestation was found to be lowest for PA, followed by LC. Deforestation rates for all land uses tended to be highest for locations that share the characteristics of areas in which TC or OC are located (e.g. degraded areas), suggesting that these areas are inherently more susceptible to deforestation due to foregone opportunities. Our approach provides important insights into how multifunctional landscapes can be designed to enhance the protection of biodiversity.

  14. Advanced Multifunctional MMOD Shield: Radiation Shielding Assessment

    NASA Technical Reports Server (NTRS)

    Rojdev, Kristina; Christiansen, Eric

    2013-01-01

    As NASA is looking to explore further into deep space, multifunctional materials are a necessity for decreasing complexity and mass. One area where multifunctional materials could be extremely beneficial is in the micrometeoroid orbital debris (MMOD) shield. A typical MMOD shield on the International Space Station (ISS) is a stuffed whipple shield consisting of multiple layers. One of those layers is the thermal blanket, or multi-layer insulation (MLI). Increasing the MMOD effectiveness of MLI blankets, while still preserving their thermal capabilities, could allow for a less massive MMOD shield. Thus, a study was conducted to evaluate a concept MLI blanket for an MMOD shield. In conjunction, this MLI blanket and the subsequent MMOD shield was also evaluated for its radiation shielding effectiveness towards protecting crew. The overall MMOD shielding system using the concept MLI blanket proved to only have a marginal increase in the radiation mitigating properties. Therefore, subsequent analysis was performed on various conceptual MMOD shields to determine the combination of materials that may prove superior for radiation mitigating purposes. The following paper outlines the evaluations performed and discusses the results and conclusions of this evaluation for radiation shielding effectiveness.

  15. Multifunctional porous silicon nanoparticles for cancer theranostics.

    PubMed

    Wang, Chang-Fang; Sarparanta, Mirkka P; Mäkilä, Ermei M; Hyvönen, Maija L K; Laakkonen, Pirjo M; Salonen, Jarno J; Hirvonen, Jouni T; Airaksinen, Anu J; Santos, Hélder A

    2015-04-01

    Nanomaterials provide a unique platform for the development of theranostic systems that combine diagnostic imaging modalities with a therapeutic payload in a single probe. In this work, dual-labeled iRGD-modified multifunctional porous silicon nanoparticles (PSi NPs) were prepared from dibenzocyclooctyl (DBCO) modified PSi NPs by strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Hydrophobic antiangiogenic drug, sorafenib, was loaded into the modified PSi NPs to enhance the drug dissolution rate and improve cancer therapy. Radiolabeling of the developed system with (111)In enabled the monitoring of the in vivo biodistribution of the nanocarrier by single photon emission computed tomography (SPECT) in an ectopic PC3-MM2 mouse xenograft model. Fluorescent labeling with Alexa Fluor 488 was used to determine the long-term biodistribution of the nanocarrier by immunofluorescence at the tissue level ex vivo. Modification of the PSi NPs with an iRGD peptide enhanced the tumor uptake of the NPs when administered intravenously. After intratumoral delivery the NPs were retained in the tumor, resulting in efficient tumor growth suppression with particle-loaded sorafenib compared to the free drug. The presented multifunctional PSi NPs highlight the utility of constructing a theranostic nanosystems for simultaneous investigations of the in vivo behavior of the nanocarriers and their drug delivery efficiency, facilitating the selection of the most promising materials for further NP development. PMID:25701036

  16. Fluorescent ampicillin analogues as multifunctional disguising agents against opsonization

    NASA Astrophysics Data System (ADS)

    Kotagiri, Nalinikanth; Sakon, Joshua; Han, Haewook; Zharov, Vladimir P.; Kim, Jin-Woo

    2016-06-01

    Cancer nanomedicines are opening new paradigms in cancer management and recent research points to how they can vastly improve imaging and therapy through multimodality and multifunctionality. However, challenges to achieving optimal efficacy are manifold starting from processing materials and evaluating their intended effectiveness on biological tissue, to developing new strategies aimed at improving transport of these materials through the biological milieu to the target tissue. Here, we report a fluorescent derivative of a beta-lactam antibiotic, ampicillin (termed iAmp) and its multifunctional physicobiochemical characteristics and potential as a biocompatible shielding agent and an effective dispersant. Carbon nanotubes (CNTs) were chosen to demonstrate the efficacy of iAmp. CNTs are known for their versatility and have been used extensively for cancer theranostics as photothermal and photoacoustic agents, but have limited solubility in water and biocompatibility. Traditional dispersants are associated with imaging artifacts and are not fully biocompatible. The chemical structure of iAmp is consistent with a deamination product of ampicillin. Although the four-membered lactam ring is intact, it does not retain the antibiotic properties. The iAmp is an effective dispersant and simultaneously serves as a fluorescent label for single-walled CNTs (SWNTs) with minimal photobleaching. The iAmp also enables bioconjugation of SWNTs to bio-ligands such as antibodies through functional carboxyl groups. Viability tests show that iAmp-coated SWNTs have minimal toxicity. Bio-stability tests under physiological conditions reveal that iAmp coating not only remains stable in a biologically relevant environment with high protein and salt concentrations, but also renders SWNTs transparent against nonspecific protein adsorption, also known as protein corona. Mammalian tissue culture studies with macrophages and opsonins validate that iAmp coating affords immunological resistance

  17. Why Go Modular? A Review of Modular A-Level Mathematics.

    ERIC Educational Resources Information Center

    Taverner, Sally; Wright, Martin

    1997-01-01

    Attitudes, academic intentions, and attainment of students gaining a grade in A-level (Advanced level) mathematics were compared for those who followed a modular course and those assessed at the end of two years of study. Overall, the final grades of those assessed modularly were half a grade higher. (JOW)

  18. Fibrous Hydrogels for Cell Encapsulation: A Modular and Supramolecular Approach

    PubMed Central

    Włodarczyk-Biegun, Małgorzata K.; Farbod, Kambiz; Werten, Marc W. T.; Slingerland, Cornelis J.; de Wolf, Frits A.; van den Beucken, Jeroen J. J. P.; Leeuwenburgh, Sander C. G.; Cohen Stuart, Martien A.; Kamperman, Marleen

    2016-01-01

    Artificial 3-dimensional (3D) cell culture systems, which mimic the extracellular matrix (ECM), hold great potential as models to study cellular processes under controlled conditions. The natural ECM is a 3D structure composed of a fibrous hydrogel that provides both mechanical and biochemical cues to instruct cell behavior. Here we present an ECM-mimicking genetically engineered protein-based hydrogel as a 3D cell culture system that combines several key features: (1) Mild and straightforward encapsulation meters (1) ease of ut I am not so sure.encapsulation of the cells, without the need of an external crosslinker. (2) Supramolecular assembly resulting in a fibrous architecture that recapitulates some of the unique mechanical characteristics of the ECM, i.e. strain-stiffening and self-healing behavior. (3) A modular approach allowing controlled incorporation of the biochemical cue density (integrin binding RGD domains). We tested the gels by encapsulating MG-63 osteoblastic cells and found that encapsulated cells not only respond to higher RGD density, but also to overall gel concentration. Cells in 1% and 2% (weight fraction) protein gels showed spreading and proliferation, provided a relative RGD density of at least 50%. In contrast, in 4% gels very little spreading and proliferation occurred, even for a relative RGD density of 100%. The independent control over both mechanical and biochemical cues obtained in this modular approach renders our hydrogels suitable to study cellular responses under highly defined conditions. PMID:27223105

  19. Fibrous Hydrogels for Cell Encapsulation: A Modular and Supramolecular Approach.

    PubMed

    Włodarczyk-Biegun, Małgorzata K; Farbod, Kambiz; Werten, Marc W T; Slingerland, Cornelis J; de Wolf, Frits A; van den Beucken, Jeroen J J P; Leeuwenburgh, Sander C G; Cohen Stuart, Martien A; Kamperman, Marleen

    2016-01-01

    Artificial 3-dimensional (3D) cell culture systems, which mimic the extracellular matrix (ECM), hold great potential as models to study cellular processes under controlled conditions. The natural ECM is a 3D structure composed of a fibrous hydrogel that provides both mechanical and biochemical cues to instruct cell behavior. Here we present an ECM-mimicking genetically engineered protein-based hydrogel as a 3D cell culture system that combines several key features: (1) Mild and straightforward encapsulation meters (1) ease of ut I am not so sure.encapsulation of the cells, without the need of an external crosslinker. (2) Supramolecular assembly resulting in a fibrous architecture that recapitulates some of the unique mechanical characteristics of the ECM, i.e. strain-stiffening and self-healing behavior. (3) A modular approach allowing controlled incorporation of the biochemical cue density (integrin binding RGD domains). We tested the gels by encapsulating MG-63 osteoblastic cells and found that encapsulated cells not only respond to higher RGD density, but also to overall gel concentration. Cells in 1% and 2% (weight fraction) protein gels showed spreading and proliferation, provided a relative RGD density of at least 50%. In contrast, in 4% gels very little spreading and proliferation occurred, even for a relative RGD density of 100%. The independent control over both mechanical and biochemical cues obtained in this modular approach renders our hydrogels suitable to study cellular responses under highly defined conditions. PMID:27223105

  20. Modular microfluidics for point-of-care biochemical purifications

    DOE PAGESBeta

    Millet, Larry J; Standaert, Robert F; Retterer, Scott T; Doktycz, Mitchel John

    2015-01-01

    Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured tomore » suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.« less

  1. Multipurpose modular lentiviral vectors for RNA interference and transgene expression.

    PubMed

    Kesireddy, Venu; van der Ven, Peter F M; Fürst, Dieter O

    2010-07-01

    We have created a multipurpose modular lentiviral vector system for expressing both transgenes and miRNA 30-based short hairpins (shRNAmirs) for RNAi. The core of the resulting vector system, pLVmir, allows a simple two step cloning procedure for expressing shRNAmirs under the control of a Pol II promoter in both a constitutive and conditional manner. The adapted cloning method includes a PCR-free method for transferring shRNAmir based RNAi clones from a publicly available library (Open Biosystems). The addition of a Pol II promoter-driven shRNAmir cassette and broadening the choice of Pol III promoters and silencing triggers offers great flexibility to this system. The combination of several preexisting and additional modules created here caters to common needs of researchers. Our modular vector system was validated regarding functionality of promoters, inducibility and reversibility. We successfully applied the system to knockdown Xirp2 mRNA expression in H2kb-tsA58 muscle cells and determined that this had no spurious effect on the expression of a closely related protein. Finally, our set of lentiviral vectors may be used to achieve synergistic effects, for simultaneous knockdown of two genes, as a rescue plasmid and for studying mutant proteins in a physiological context. PMID:19798586

  2. Advanced Modular Inverter Technology Development

    SciTech Connect

    Adam Szczepanek

    2006-02-04

    Electric and hybrid-electric vehicle systems require an inverter to convert the direct current (DC) output of the energy generation/storage system (engine, fuel cells, or batteries) to the alternating current (AC) that vehicle propulsion motors use. Vehicle support systems, such as lights and air conditioning, also use the inverter AC output. Distributed energy systems require an inverter to provide the high quality AC output that energy system customers demand. Today's inverters are expensive due to the cost of the power electronics components, and system designers must also tailor the inverter for individual applications. Thus, the benefits of mass production are not available, resulting in high initial procurement costs as well as high inverter maintenance and repair costs. Electricore, Inc. (www.electricore.org) a public good 501 (c) (3) not-for-profit advanced technology development consortium assembled a highly qualified team consisting of AeroVironment Inc. (www.aerovironment.com) and Delphi Automotive Systems LLC (Delphi), (www.delphi.com), as equal tiered technical leads, to develop an advanced, modular construction, inverter packaging technology that will offer a 30% cost reduction over conventional designs adding to the development of energy conversion technologies for crosscutting applications in the building, industry, transportation, and utility sectors. The proposed inverter allows for a reduction of weight and size of power electronics in the above-mentioned sectors and is scalable over the range of 15 to 500kW. The main objective of this program was to optimize existing AeroVironment inverter technology to improve power density, reliability and producibility as well as develop new topology to reduce line filter size. The newly developed inverter design will be used in automotive and distribution generation applications. In the first part of this program the high-density power stages were redesigned, optimized and fabricated. One of the main tasks

  3. Modular Manufacturing Simulator: Users Manual

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Modular Manufacturing Simulator (MMS) has been developed for the beginning user of computer simulations. Consequently, the MMS cannot model complex systems that require branching and convergence logic. Once a user becomes more proficient in computer simulation and wants to add more complexity, the user is encouraged to use one of the many available commercial simulation systems. The (MMS) is based on the SSE5 that was developed in the early 1990's by the University of Alabama in Huntsville (UAH). A recent survey by MSFC indicated that the simulator has been a major contributor to the economic impact of the MSFC technology transfer program. Many manufacturers have requested additional features for the SSE5. Consequently, the following features have been added to the MMS that are not available in the SSE5: runs under Windows, print option for both input parameters and output statistics, operator can be fixed at a station or assigned to a group of stations, operator movement based on time limit, part limit, or work-in-process (WIP) limit at next station. The movement options for a moveable operators are: go to station with largest WIP, rabbit chase where operator moves in circular sequence between stations, and push/pull where operator moves back and forth between stations. This user's manual contains the necessary information for installing the MMS on a PC, a description of the various MMS commands, and the solutions to a number of sample problems using the MMS. Also included in the beginning of this report is a brief discussion of technology transfer.

  4. Teleoperated Modular Robots for Lunar Operations

    NASA Technical Reports Server (NTRS)

    Globus, Al; Hornby, Greg; Larchev, Greg; Hancher, Matt; Cannon, Howard; Lohn, Jason

    2004-01-01

    Solar system exploration is currently carried out by special purpose robots exquisitely designed for the anticipated tasks. However, all contingencies for in situ resource utilization (ISRU), human habitat preparation, and exploration will be difficult to anticipate. Furthermore, developing the necessary special purpose mechanisms for deployment and other capabilities is difficult and error prone. For example, the Galileo high gain antenna never opened, severely restricting the quantity of data returned by the spacecraft. Also, deployment hardware is used only once. To address these problems, we are developing teleoperated modular robots for lunar missions, including operations in transit from Earth. Teleoperation of lunar systems from Earth involves a three second speed-of-light delay, but experiment suggests that interactive operations are feasible.' Modular robots typically consist of many identical modules that pass power and data between them and can be reconfigured for different tasks providing great flexibility, inherent redundancy and graceful degradation as modules fail. Our design features a number of different hub, link, and joint modules to simplify the individual modules, lower structure cost, and provide specialized capabilities. Modular robots are well suited for space applications because of their extreme flexibility, inherent redundancy, high-density packing, and opportunities for mass production. Simple structural modules can be manufactured from lunar regolith in situ using molds or directed solar sintering. Software to direct and control modular robots is difficult to develop. We have used genetic algorithms to evolve both the morphology and control system for walking modular robots3 We are currently using evolvable system technology to evolve controllers for modular robots in the ISS glove box. Development of lunar modular robots will require software and physical simulators, including regolith simulation, to enable design and test of robot

  5. Modular and Versatile Spatial Functionalization of Tissue Engineering Scaffolds through Fiber‐Initiated Controlled Radical Polymerization

    PubMed Central

    Harrison, Rachael H.; Steele, Joseph A. M.; Chapman, Robert; Gormley, Adam J.; Chow, Lesley W.; Mahat, Muzamir M.; Podhorska, Lucia; Palgrave, Robert G.; Payne, David J.; Hettiaratchy, Shehan P.; Dunlop, Iain E.

    2015-01-01

    Native tissues are typically heterogeneous and hierarchically organized, and generating scaffolds that can mimic these properties is critical for tissue engineering applications. By uniquely combining controlled radical polymerization (CRP), end‐functionalization of polymers, and advanced electrospinning techniques, a modular and versatile approach is introduced to generate scaffolds with spatially organized functionality. Poly‐ε‐caprolactone is end functionalized with either a polymerization‐initiating group or a cell‐binding peptide motif cyclic Arg‐Gly‐Asp‐Ser (cRGDS), and are each sequentially electrospun to produce zonally discrete bilayers within a continuous fiber scaffold. The polymerization‐initiating group is then used to graft an antifouling polymer bottlebrush based on poly(ethylene glycol) from the fiber surface using CRP exclusively within one bilayer of the scaffold. The ability to include additional multifunctionality during CRP is showcased by integrating a biotinylated monomer unit into the polymerization step allowing postmodification of the scaffold with streptavidin‐coupled moieties. These combined processing techniques result in an effective bilayered and dual‐functionality scaffold with a cell‐adhesive surface and an opposing antifouling non‐cell‐adhesive surface in zonally specific regions across the thickness of the scaffold, demonstrated through fluorescent labelling and cell adhesion studies. This modular and versatile approach combines strategies to produce scaffolds with tailorable properties for many applications in tissue engineering and regenerative medicine. PMID:27134621

  6. Biotic homogenization can decrease landscape-scale forest multifunctionality.

    PubMed

    van der Plas, Fons; Manning, Pete; Soliveres, Santiago; Allan, Eric; Scherer-Lorenzen, Michael; Verheyen, Kris; Wirth, Christian; Zavala, Miguel A; Ampoorter, Evy; Baeten, Lander; Barbaro, Luc; Bauhus, Jürgen; Benavides, Raquel; Benneter, Adam; Bonal, Damien; Bouriaud, Olivier; Bruelheide, Helge; Bussotti, Filippo; Carnol, Monique; Castagneyrol, Bastien; Charbonnier, Yohan; Coomes, David Anthony; Coppi, Andrea; Bastias, Cristina C; Dawud, Seid Muhie; De Wandeler, Hans; Domisch, Timo; Finér, Leena; Gessler, Arthur; Granier, André; Grossiord, Charlotte; Guyot, Virginie; Hättenschwiler, Stephan; Jactel, Hervé; Jaroszewicz, Bogdan; Joly, François-Xavier; Jucker, Tommaso; Koricheva, Julia; Milligan, Harriet; Mueller, Sandra; Muys, Bart; Nguyen, Diem; Pollastrini, Martina; Ratcliffe, Sophia; Raulund-Rasmussen, Karsten; Selvi, Federico; Stenlid, Jan; Valladares, Fernando; Vesterdal, Lars; Zielínski, Dawid; Fischer, Markus

    2016-03-29

    Many experiments have shown that local biodiversity loss impairs the ability of ecosystems to maintain multiple ecosystem functions at high levels (multifunctionality). In contrast, the role of biodiversity in driving ecosystem multifunctionality at landscape scales remains unresolved. We used a comprehensive pan-European dataset, including 16 ecosystem functions measured in 209 forest plots across six European countries, and performed simulations to investigate how local plot-scale richness of tree species (α-diversity) and their turnover between plots (β-diversity) are related to landscape-scale multifunctionality. After accounting for variation in environmental conditions, we found that relationships between α-diversity and landscape-scale multifunctionality varied from positive to negative depending on the multifunctionality metric used. In contrast, when significant, relationships between β-diversity and landscape-scale multifunctionality were always positive, because a high spatial turnover in species composition was closely related to a high spatial turnover in functions that were supported at high levels. Our findings have major implications for forest management and indicate that biotic homogenization can have previously unrecognized and negative consequences for large-scale ecosystem multifunctionality. PMID:26979952

  7. The frequency-agile radar: A multifunctional approach to remote sensing of the ionosphere

    NASA Astrophysics Data System (ADS)

    Tsunoda, R. T.; Livingston, R. C.; Buonocore, J. J.; McKinley, A. V.

    1995-09-01

    We introduce a new kind of diagnostic sensor that combines multifunctional measurement capabilities for ionospheric research. Multifunctionality is realized through agility in frequency selection over an extended band (1.5 to 50 MHz), system modularity, complete system control by software written in C, and a user-friendly computer interface. This sensor, which we call the frequency-agile radar (FAR), incorporates dual radar channels and an arbitrary waveform synthesizer that allows creative design of sophisticated waveforms as a means of increasing its sensitivity to weak signals while minimizing loss in radar resolution. The sensitivity of the FAR is determined by two sets of power amplifier modules: four 4-kW solid-state broadband amplifiers, and four 30-kW vacuum tube amplifiers. FAR control is by an AT-bus personal computer with on-line processing by a programmable array processor. The FAR does not simply house the separate functions of most radio sensors in use today, it provides convenient and flexible access to those functions as elements to be used in any combination. Some of the first new results obtained with the FAR during recent field campaigns are presented to illustrate its versatility. These include (1) the first detection of anomalous high-frequency (HF) reflections from a barium ion cloud, (2) the first evidence of unexpectedly large drifts and a shear north of the equatorial electrojet, (3) the first HF radar signature of a developing equatorial plasma bubble, and (4) the first measurements by a portable radar of altitude-extended, quasi-periodic backscatter from midlatitude sporadic E. We also mention the potential of the FAR for atmospheric remote sensing.

  8. Supramolecular chemistry at interfaces: host-guest interactions for fabricating multifunctional biointerfaces.

    PubMed

    Yang, Hui; Yuan, Bin; Zhang, Xi; Scherman, Oren A

    2014-07-15

    CONSPECTUS: Host-guest chemistry can greatly improve the selectivity of biomolecule-ligand binding on account of recognition-directed interactions. In addition, functional structures and the actuation of supramolecular assemblies in molecular systems can be controlled efficiently through various host-guest chemistry. Together, these highly selective, strong yet dynamic interactions can be exploited as an alternative methodology for applications in the field of programmable and controllable engineering of supramolecular soft materials through the reversible binding between complementary components. Many processes in living systems such as biotransformation, transportation of matter, and energy transduction begin with interfacial molecular recognition, which is greatly influenced by various external stimuli at biointerfaces. Detailed investigations about the molecular recognition at interfaces can result in a better understanding of life science, and further guide us in developing new biomaterials and medicines. In order to mimic complicated molecular-recognition systems observed in nature that adapt to changes in their environment, combining host-guest chemistry and surface science is critical for fabricating the next generation of multifunctional biointerfaces with efficient stimuli-responsiveness and good biocompatibility. In this Account, we will summarize some recent progress on multifunctional stimuli-responsive biointerfaces and biosurfaces fabricated by cyclodextrin- or cucurbituril-based host-guest chemistry and highlight their potential applications including drug delivery, bioelectrocatalysis, and reversible adsorption and resistance of peptides, proteins, and cells. In addition, these biointerfaces and biosurfaces demonstrate efficient response toward various external stimuli, such as UV light, pH, redox chemistry, and competitive guests. All of these external stimuli can aid in mimicking the biological stimuli evident in complex biological environments

  9. Post-Translational Modification of Bionanoparticles as a Modular Platform for Biosensor Assembly.

    PubMed

    Sun, Qing; Chen, Qi; Blackstock, Daniel; Chen, Wilfred

    2015-08-25

    Context driven biosensor assembly with modular targeting and detection moieties is gaining significant attentions. Although protein-based nanoparticles have emerged as an excellent platform for biosensor assembly, current strategies of decorating bionanoparticles with targeting and detection moieties often suffer from unfavorable spacing and orientation as well as bionanoparticle aggregation. Herein, we report a highly modular post-translational modification approach for biosensor assembly based on sortase A-mediated ligation. This approach enables the simultaneous modifications of the Bacillus stearothermophilus E2 nanoparticles with different functional moieties for antibody, enzyme, DNA aptamer, and dye decoration. The resulting easy-purification platform offers a high degree of targeting and detection modularity with signal amplification. This flexibility is demonstrated for the detection of both immobilized antigens and cancer cells. PMID:26235232

  10. Next-Generation Multifunctional Electrochromic Devices.

    PubMed

    Cai, Guofa; Wang, Jiangxin; Lee, Pooi See

    2016-08-16

    The rational design and exploration of electrochromic devices will find a wide range of applications in smart windows for energy-efficient buildings, low-power displays, self-dimming rear mirrors for automobiles, electrochromic e-skins, and so on. Electrochromic devices generally consist of multilayer structures with transparent conductors, electrochromic films, ion conductors, and ion storage films. Synthetic strategies and new materials for electrochromic films and transparent conductors, comprehensive electrochemical kinetic analysis, and novel device design are areas of active study worldwide. These are believed to be the key factors that will help to significantly improve the electrochromic performance and extend their application areas. In this Account, we present our strategies to design and fabricate electrochromic devices with high performance and multifunctionality. We first describe the synthetic strategies, in which a porous tungsten oxide (WO3) film with nearly ideal optical modulation and fast switching was prepared by a pulsed electrochemical deposition method. Multiple strategies, such as sol-gel/inkjet printing methods, hydrothermal/inkjet printing methods, and a novel hybrid transparent conductor/electrochromic layer have been developed to prepare high-performance electrochromic films. We then summarize the recent advances in transparent conductors and ion conductor layers, which play critial roles in electrochromic devices. Benefiting from the developments of soft transparent conductive substrates, highly deformable electrochromic devices that are flexible, foldable, stretchable, and wearable have been achieved. These emerging devices have great potential in applications such as soft displays, electrochromic e-skins, deformable electrochromic films, and so on. We finally present a concept of multifunctional smart glass, which can change its color to dynamically adjust the daylight and solar heat input of the building or protect the users' privacy

  11. Biogenesis of the multifunctional lipid droplet: Lipids, proteins, and sites

    PubMed Central

    Gross, Steven P.

    2014-01-01

    Lipid droplets (LDs) are ubiquitous dynamic organelles that store and supply lipids in all eukaryotic and some prokaryotic cells for energy metabolism, membrane synthesis, and production of essential lipid-derived molecules. Interest in the organelle’s cell biology has exponentially increased over the last decade due to the link between LDs and prevalent human diseases and the discovery of new and unexpected functions of LDs. As a result, there has been significant recent progress toward understanding where and how LDs are formed, and the specific lipid pathways that coordinate LD biogenesis. PMID:24590170

  12. Computing an upper bound of modularity

    NASA Astrophysics Data System (ADS)

    Miyauchi, Atsushi; Miyamoto, Yuichiro

    2013-07-01

    Modularity proposed by Newman and Girvan is a quality function for community detection. Numerous heuristics for modularity maximization have been proposed because the problem is NP-hard. However, the accuracy of these heuristics has yet to be properly evaluated because computational experiments typically use large networks whose optimal modularity is unknown. In this study, we propose two powerful methods for computing a nontrivial upper bound of modularity. More precisely, our methods can obtain the optimal value of a linear programming relaxation of the standard integer linear programming for modularity maximization. The first method modifies the traditional row generation approach proposed by Grötschel and Wakabayashi to shorten the computation time. The second method is based on a row and column generation. In this method, we first solve a significantly small subproblem of the linear programming and iteratively add rows and columns. Owing to the speed and memory efficiency of these proposed methods, they are suitable for large networks. In particular, the second method consumes exceedingly small memory capacity, enabling us to compute the optimal value of the linear programming for the Power Grid network (consisting of 4941 vertices and 6594 edges) on a standard desktop computer.

  13. Multifunctional nanoparticles as coupled contrast agents

    PubMed Central

    Jin, Yongdong; Jia, Congxian; Huang, Sheng-Wen; O’Donnell, Matthew; Gao, Xiaohu

    2011-01-01

    Engineering compact imaging probes with highly integrated modalities is a key focus in bionanotechnology and will have profound impact on molecular diagnostics, imaging, and therapeutics. However, combining multiple components on a nanometer scale to create new imaging modalities unavailable from individual components has proven challenging. Here, we demonstrate iron oxide and gold coupled core-shell nanoparticles with well defined structural characteristics (e.g., size, shell thickness, and core-shell separation) and physical properties (e.g., electronic, magnetic, optical, thermal, and acoustic). The resulting multifunctional nanoprobes not only offer contrast for electron microscopy, magnetic resonance imaging, and scattering-based imaging, but more importantly, enable a new imaging mode, magnetomotive photoacoustic (mmPA) imaging, with remarkable contrast enhancement compared to PA images using conventional nanoparticle contrast agents. PMID:20975706

  14. Multifunctional iron oxide nanoparticles for biomedical applications

    NASA Astrophysics Data System (ADS)

    Bloemen, M.; Denis, C.; Van Stappen, T.; De Meester, L.; Geukens, N.; Gils, A.; Verbiest, T.

    2015-03-01

    Multifunctional nanoparticles have attracted a lot of attention since they can combine interesting properties like magnetism, fluorescence or plasmonic effects. As a core material, iron oxide nanoparticles have been the subject of intensive research. These cost-effective and non-toxic particles are used nowadays in many applications. We developed a heterobifunctional PEG ligand that can be used to introduce functional groups (carboxylic acids) onto the surface of the NP. Via click chemistry, a siloxane functionality was added to this ligand, for a subsequent covalent ligand exchange reaction. The functionalized nanoparticles have an excellent colloidal stability in complex environments like buffers and serum or plasma. Antibodies were coupled to the introduced carboxylic acids and these NP-antibody bioconjugates were brought into contact with Legionella bacteria for magnetic separation experiments.

  15. Multiscale Multifunctional Progressive Fracture of Composite Structures

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Minnetyan, L.

    2012-01-01

    A new approach is described for evaluating fracture in composite structures. This approach is independent of classical fracture mechanics parameters like fracture toughness. It relies on computational simulation and is programmed in a stand-alone integrated computer code. It is multiscale, multifunctional because it includes composite mechanics for the composite behavior and finite element analysis for predicting the structural response. It contains seven modules; layered composite mechanics (micro, macro, laminate), finite element, updating scheme, local fracture, global fracture, stress based failure modes, and fracture progression. The computer code is called CODSTRAN (Composite Durability Structural ANalysis). It is used in the present paper to evaluate the global fracture of four composite shell problems and one composite built-up structure. Results show that the composite shells. Global fracture is enhanced when internal pressure is combined with shear loads. The old reference denotes that nothing has been added to this comprehensive report since then.

  16. AEGIS - Advanced Multi-Function Array Radar

    NASA Astrophysics Data System (ADS)

    Phillips, C. C.

    1981-12-01

    The AMFAR (Advanced Multi-Function Array Radar), a radar system technology developed in the late 1960s, has demonstrated automatic detection and tracking of all air targets plus inherent resistance to natural and man-made clutter with computer control of the radar. The major elements of the AMFAR - a high-power radar frequency transmitter, a phased-array antenna, a signal processor system, a computer control system, and an automated test system - are described in detail. The capabilities of the radar are demonstrated in a series of pictures showing processing steps to provide automatic target detection and track in both ground clutter zones and rain clutter. The success of AMFAR laid the foundation of Radar System AN/SPY-1A, the Weapon Control Radar System now being produced as a major element of the AEGIS Weapon System for the U.S. Navy guided missile cruiser Ticonderoga.

  17. Overview of GSE as a multifunctional GUI

    NASA Astrophysics Data System (ADS)

    Kurtovich, Boyan; Malangone, Fabio; Voss, David L.; Carssow, Douglas B.; Fritz, Theodore A.; Mavretic, Anton

    2009-08-01

    Ground Support Equipment (GSE) [1] is a versatile and multifunctional graphical user interface (GUI) and a software/hardware platform. It is a custom-designed system executed in the LabVIEW programming language to serve as an instrument health monitor for the Loss Cone Imager (LCI) satellite project. GSE mimics the behavior of the onboard Experiment Computer System (ECS). Its functions comprise the measurement of voltage, current, and power, as well as acting as a safety mechanism in case of any anomalous condition (e.g., over-current and/or over-voltage situation). Individual log files record the sessions during which data is gathered and analyzed. Safety/warning alarm flags shall be 'visible' from any individual window/tab. Analog-to-Digital Conversion (ADC) particle group measurements will be displayed on six individual panels. GSE will be supplemented with a comprehensive user's manual for added clarity.

  18. Photopolymeric multifunctional dendrimer toward holographic applications.

    PubMed

    Jeong, Yong-Cheol; Jung, Bokyung; Park, Jung-Ki

    2012-09-26

    We present a photopolymeric multifunctional dendrimer for holographic applications. In this study, we described a synthesis of multiphotoreactive dendrimer and phase compatible polymer matrix as well as a numerical simulation of the dendrimer. This holographic photopolymer containing a nanosized photoreactive organic dendrimer could address the aggregation issue of conventional inorganic nanoparticle additives and allowed writing-induced shrinkage to be successfully reduced to the extent of acceptable values for 130 μm thick film. In this report, holographic performance including diffraction efficiency (DE), transmission, photosensitivity, modulation of refractive index, polarization sensitivity, and volume shrinkage has been discussed. The page-wise recording by using an amplitude spatial light modulator (SLM) was also demonstrated. PMID:22950741

  19. Multifunctional pulse sequence generator for pulse NMR

    NASA Astrophysics Data System (ADS)

    Wang, Dongsheng

    1988-06-01

    A new multifunctional pulse sequence generator has been designed and constructed. It can conveniently generate various pulse sequences used in nuclear-magnetic resonance (NMR) to measure the spin-lattice relaxation time T1, the spin-spin relaxation time T2, and the spin-locking relaxation time T1 ρ. It can also be used in pulse Fourier transform NMR and double resonance. The intervals of pulses can increase automatically with sequence repetitions and the generator can be used in two-dimensional spectrum measurement and spin-density imaging research. The sequences can be generated through four different triggering methods and there are two synchronous pulse outputs and fifteen auxiliary pulse outputs, so the generator can be conveniently interfaced with a computer or other instruments. The circuitry, functions, and features of the generator are described in this article.

  20. Artificial neural network for multifunctional areas.

    PubMed

    Riccioli, Francesco; El Asmar, Toufic; El Asmar, Jean-Pierre; Fagarazzi, Claudio; Casini, Leonardo

    2016-01-01

    The issues related to the appropriate planning of the territory are particularly pronounced in highly inhabited areas (urban areas), where in addition to protecting the environment, it is important to consider an anthropogenic (urban) development placed in the context of sustainable growth. This work aims at mathematically simulating the changes in the land use, by implementing an artificial neural network (ANN) model. More specifically, it will analyze how the increase of urban areas will develop and whether this development would impact on areas with particular socioeconomic and environmental value, defined as multifunctional areas. The simulation is applied to the Chianti Area, located in the province of Florence, in Italy. Chianti is an area with a unique landscape, and its territorial planning requires a careful examination of the territory in which it is inserted. PMID:26718948

  1. Multifunctional composite core-shell nanoparticles

    NASA Astrophysics Data System (ADS)

    Wei, Suying; Wang, Qiang; Zhu, Jiahua; Sun, Luyi; Lin, Hongfei; Guo, Zhanhu

    2011-11-01

    In this review paper, the state-of-the-art knowledge of the core-shell multifunctional nanoparticles (MNPs), especially with unique physiochemical properties, is presented. The synthesis methods were summarized from the aspects of both the advantages and the demerits. The core includes the inexpensive and easily oxidized metals and the noble shells include the relatively noble metals, carbon, silica, other oxides, and polymers. The properties including magnetic, optical, anti-corrosion and the surface chemistry of the NPs are thoroughly reviewed. The current status of the applications is reviewed with the detailed examples including the catalysis, giant magnetoresistance (GMR) sensing, electromagnetic interface shielding or microwave absorption, biomedical drug delivery, and the environmental remediation.

  2. Multifunctional Micellar Nanomedicine for Cancer Therapy

    PubMed Central

    Blanco, Elvin; Kessinger, Chase W.; Sumer, Baran D.; Gao, Jinming

    2010-01-01

    Polymeric micelles are supramolecular, core-shell nanoparticles that offer considerable advantages for cancer diagnosis and therapy. Their relatively small size (10-100 nm), ability to solubilize hydrophobic drugs as well as imaging agents, and improved pharmacokinetics provide a useful bioengineering platform for cancer applications. Several polymeric micelle formulations are currently undergoing phase I/II clinical trials, which have shown improved antitumor efficacy and reduced systemic toxicity. This minireview will focus on recent advancements in the multifunctional design of micellar nanomedicine with tumor targeting, stimulated drug release, and cancer imaging capabilities. Such functionalization strategies result in enhanced micellar accumulation at tumor sites, higher drug bioavailability, as well as improved tumor diagnosis and visualization of therapy. Ultimately, integrated nanotherapeutic systems (e.g., theranostic nanomedicine) may prove essential to address the challenges of tumor heterogeneity and adaptive resistance to achieve efficacious treatment of cancer. PMID:19064945

  3. On Multifunctional Collaborative Methods in Engineering Science

    NASA Technical Reports Server (NTRS)

    Ransom, Jonathan B.

    2001-01-01

    Multifunctional methodologies and analysis procedures are formulated for interfacing diverse subdomain idealizations including multi-fidelity modeling methods and multi-discipline analysis methods. These methods, based on the method of weighted residuals, ensure accurate compatibility of primary and secondary variables across the subdomain interfaces. Methods are developed using diverse mathematical modeling (i.e., finite difference and finite element methods) and multi-fidelity modeling among the subdomains. Several benchmark scalar-field and vector-field problems in engineering science are presented with extensions to multidisciplinary problems. Results for all problems presented are in overall good agreement with the exact analytical solution or the reference numerical solution. Based on the results, the integrated modeling approach using the finite element method for multi-fidelity discretization among the subdomains is identified as most robust. The multiple method approach is advantageous when interfacing diverse disciplines in which each of the method's strengths are utilized.

  4. 3D Multifunctional Ablative Thermal Protection System

    NASA Technical Reports Server (NTRS)

    Feldman, Jay; Venkatapathy, Ethiraj; Wilkinson, Curt; Mercer, Ken

    2015-01-01

    NASA is developing the Orion spacecraft to carry astronauts farther into the solar system than ever before, with human exploration of Mars as its ultimate goal. One of the technologies required to enable this advanced, Apollo-shaped capsule is a 3-dimensional quartz fiber composite for the vehicle's compression pad. During its mission, the compression pad serves first as a structural component and later as an ablative heat shield, partially consumed on Earth re-entry. This presentation will summarize the development of a new 3D quartz cyanate ester composite material, 3-Dimensional Multifunctional Ablative Thermal Protection System (3D-MAT), designed to meet the mission requirements for the Orion compression pad. Manufacturing development, aerothermal (arc-jet) testing, structural performance, and the overall status of material development for the 2018 EM-1 flight test will be discussed.

  5. Multifunctional carbon nanohorn complexes for cancer treatment.

    PubMed

    Chechetka, Svetlana A; Pichon, Benoit; Zhang, Minfang; Yudasaka, Masako; Bégin-Colin, Sylvie; Bianco, Alberto; Miyako, Eijiro

    2015-01-01

    Multifunctional carbon nanohorn (CNH) complexes were synthesized using oxidized CNH, magnetite (MAG) nanoparticles, and polyethyleneimine (PEI). The ferromagnetic MAG nanoparticles were loaded onto CNH (MAG-CNH) using iron(II) acetate and subsequent heat treatment. Chemical functionalization of the MAG-CNH complexes with PEI improved their water-dispersibility and allowed further conjugation with a fluorophore. The application of an external magnetic field significantly intensified the targeted vectorization of CNH complexes into human cervical cancer (HeLa) cells. Following cell uptake, laser irradiation of the cells showed a significant enhancement in the photothermal effects of CNHs leading to cell death. We have confirmed that the photothermal properties and ferromagnetic characteristics of CNH complexes show efficient cell elimination. The present study is an essential step toward the development of an innovative cancer therapy and a highly sensitive detection of cancer cells at the single-cell level. PMID:25319234

  6. Multifunctional iron-chelators with protective roles against neurodegenerative diseases.

    PubMed

    Nunes, Andreia; Marques, Sérgio M; Quintanova, Catarina; Silva, Diana F; Cardoso, Sandra M; Chaves, Sílvia; Santos, M Amélia

    2013-05-01

    The multifactorial nature of Alzheimer's disease (AD), and the absence of a disease modifying drug, makes the development of new multifunctional drugs an attractive therapeutic strategy. Taking into account the hallmarks of AD patient brains, such as low levels of acetylcholine, misfolding of proteins and associated beta-amyloid (Aβ) aggregation, oxidative stress and metal dyshomeostasis, we have developed a series of compounds that merge three different approaches: metal attenuation, anti-Aβ aggregation and anti-acetylcholinesterase activity. Therefore, 3-hydroxy-4-pyridinone (3,4-HP) and benzothiazole molecular moieties were selected as starting frameworks due to their well known affinity for iron and Aβ peptides, respectively. The linkers between these two main functional groups were selected on the basis of virtual screening, so that the final molecule could further inhibit the acetylcholinesterase, responsible for the cholinergic losses. We describe herein the design and synthesis of the new hybrid compounds, followed by the assessment of solution properties, namely iron chelation and anti-oxidant capacity. The compounds were bioassayed for their capacity to inhibit AChE, as well as self- and Zn mediated-Aβ(1-42) aggregation. Finally, we assessed their effects on the viability of neuronal cells stressed with Aβ(42). PMID:23487286

  7. Recombinant medaka (Oryzias melastigmus) pro-hepcidin: Multifunctional characterization.

    PubMed

    Cai, Ling; Cai, Jing-Jing; Liu, Hai-Peng; Fan, Dan-Qing; Peng, Hui; Wang, Ke-Jian

    2012-02-01

    Recently, two hepcidin variant genes (Om-hep1 and Om-hep2) were identified in a model fish marine medaka and both were highly induced in vivo with bacterial challenge, suggesting that the medaka hepcidin may have a similar function to other reported teleostean hepcidins. In the present study, the antibacterial, antiviral and antitumor activities of Om-hep1 were determined using its synthetic and recombinant pro-peptides. The recombinant pro-hepcidin1 was expressed in Escherichia coli and an effective method to produce recombinant Pro-Omhep1 was developed in order to obtain a right folded structure. The results showed that both the synthetic mature peptide and recombinant pro-peptide had similar antibacterial activity against Gram-positive and negative bacteria. In particular, both the synthetic mature Om-hep1 and recombinant Pro-Omhep1 inhibited the viral replication of white spot syndrome virus in the hematopoietic tissue cells of the crayfish Cherax quadricarinatus. Om-hep1 also presented antitumor activity on the cultured human hepatocellular carcinoma cells. In addition, the antimicrobial mechanism of Om-hep1 was measured and it was found that Om-hep1 was likely to be non-membranolytic. The recombinant Pro-Omhep1 performed better biological activity compared to the synthetic mature Om-hep1. This study suggested that Om-hep1 was likely to be an important multifunction protein involved in various resistance actions in the marine medaka immune system. PMID:22051539

  8. Naturally Inspired Molecules as Multifunctional Agents for Alzheimer's Disease Treatment.

    PubMed

    Rampa, Angela; Tarozzi, Andrea; Mancini, Francesca; Pruccoli, Letizia; Di Martino, Rita Maria Concetta; Gobbi, Silvia; Bisi, Alessandra; De Simone, Angela; Palomba, Francesco; Zaccheroni, Nelsi; Belluti, Federica

    2016-01-01

    Alzheimer's disease (AD) has been defined as a multi-factorial disorder resulting from a complex array of networked cellular and molecular mechanisms. In particular, elevated levels of Aβ protein and its aggregation products in the presence of metal ions proved to be highly neurotoxic and therapeutic strategies aimed at preventing Aβ generation and oxidative stress may represent an effective approach for AD treatment. A recent paradigm for the treatment of complex diseases such as AD suggests the employment of multifunctional compounds, single chemical entities capable of simultaneously modulating different targets involved in the pathology. In this paper, the "pharmacophores combination" strategy was applied, connecting the main scaffold of the BACE-1 ligand 1 to that of the chalcone 2, as metal chelating pharmacophore, to obtain a small library of compounds. Conjugate 5 emerged as the most interesting derivative, proving to inhibit BACE-1 with low-micromolar potency, and showing neuroprotective effects. In particular, 5 proved to be able to protect from metal-associated oxidative stress by hampering intracellular Cu(2+)-induced ROS formation without any direct neurotoxic effect. PMID:27196880

  9. MULTIFUNCTIONAL SOLAR ENERGY SYSTEMS RESEARCH PROJECT

    SciTech Connect

    Byard Wood, Lance Seefeldt, Ronald Sims, Bradley Wahlen, and Dan Dye

    2012-06-29

    The solar energy available within the visible portion of the solar spectrum is about 300 W/m2 (43%) and that available in the UV and IR portion is about 400 W/m2 (57%). This provides opportunities for developing integrated energy systems that capture and use specific wavelengths of the solar spectrum for different purposes. For example: biofuels from photosynthetic microbes use only the visible light; solar cells use a narrow band of the solar spectrum that could be either mostly in the visible or in the IR regions of the solar spectrum, depending on the photovoltaic materials, e.g., gallium antimonide (GaSb) cells utilize predominately IR radiation; and finally, solar panels that heat water utilize a broad range of wavelengths (visible plus IR). The basic idea of this research is that sunlight has many possible end-use applications including both direct use and energy conversion schemes; it is technically feasible to develop multifunctional solar energy systems capable of addressing several end-use needs while increasing the overall solar energy utilization efficiency when compared to single-purpose solar technologies. Such a combination of technologies could lead to more cost-competitive ?multifunctional? systems that add value and broaden opportunities for integrated energy systems. The goal of this research is to increase the overall energy efficacy and cost competitiveness of solar systems. The specific objectives of this research were: 1) Evaluate the efficacy of a combined photobioreactor and electric power system; 2) Improve the reliability and cost effectiveness of hybrid solar lighting systems ? a technology in which sunlight is collected and distributed via optical fibers into the interior of a building; 3) Evaluate the efficacy of using filtered light to increase the production of biomass in photobioreactors and provide more solar energy for other uses; 4) Evaluates several concepts for wavelength shifting such that a greater percentage of the solar

  10. Advanced Multifunctional MMOD Shield: Radiation Shielding Assessment

    NASA Technical Reports Server (NTRS)

    Rojdev, Kristina; Christiansen, Eric

    2011-01-01

    As NASA is looking to explore further into deep space, multifunctional materials are a necessity for decreasing complexity and mass. One area where multifunctional materials could be extremely beneficial is in the micrometeoroid orbital debris (MMOD) shield. A typical MMOD shield on the International Space Station (ISS) is a stuffed whipple shield consisting of multiple layers. One of those layers is the thermal blanket, or multi-layer insulation (MLI). By increasing the MMOD effectiveness of MLI blankets, while still preserving their thermal capabilities, could allow for a less massive MMOD shield. Thus, a study was conducted to evaluate concept MLI blankets for MMOD shields. In conjunction, these MLI blankets and the subsequent MMOD shields were also evaluated for their radiation shielding effectiveness towards protecting crew. These concepts were evaluated against the ISS MLI blankets and the ISS MMOD shield, which acted as the baseline. These radiation shielding assessments were performed using the high charge and energy transport software (HZETRN). This software is based on a one-dimensional formula of the Boltzmann transport equation with a straight-ahead approximation. Each configuration was evaluated against the following environments to provide a diverse view of radiation shielding effectiveness in most space environments within the heliosphere: August 1972 solar particle event, October 1989 solar particle event, 1982 galactic cosmic ray environment (during solar maximum), 1987 galactic cosmic ray environment (during solar minimum), and a low earth orbit environment in 1970 that corresponded to an altitude of 400 km and inclination of 51.6 . Both the absorbed dose and the dose equivalent were analyzed, but the focus of the discussion was on the dose equivalent since the data is most concerned with radiation shielding of the crew. The following paper outlines the evaluations performed and discusses the results and conclusions of this evaluation for

  11. A modular framework for biomedical concept recognition

    PubMed Central

    2013-01-01

    Background Concept recognition is an essential task in biomedical information extraction, presenting several complex and unsolved challenges. The development of such solutions is typically performed in an ad-hoc manner or using general information extraction frameworks, which are not optimized for the biomedical domain and normally require the integration of complex external libraries and/or the development of custom tools. Results This article presents Neji, an open source framework optimized for biomedical concept recognition built around four key characteristics: modularity, scalability, speed, and usability. It integrates modules for biomedical natural language processing, such as sentence splitting, tokenization, lemmatization, part-of-speech tagging, chunking and dependency parsing. Concept recognition is provided through dictionary matching and machine learning with normalization methods. Neji also integrates an innovative concept tree implementation, supporting overlapped concept names and respective disambiguation techniques. The most popular input and output formats, namely Pubmed XML, IeXML, CoNLL and A1, are also supported. On top of the built-in functionalities, developers and researchers can implement new processing modules or pipelines, or use the provided command-line interface tool to build their own solutions, applying the most appropriate techniques to identify heterogeneous biomedical concepts. Neji was evaluated against three gold standard corpora with heterogeneous biomedical concepts (CRAFT, AnEM and NCBI disease corpus), achieving high performance results on named entity recognition (F1-measure for overlap matching: species 95%, cell 92%, cellular components 83%, gene and proteins 76%, chemicals 65%, biological processes and molecular functions 63%, disorders 85%, and anatomical entities 82%) and on entity normalization (F1-measure for overlap name matching and correct identifier included in the returned list of identifiers: species 88

  12. Modular categories and 3-manifold invariants

    SciTech Connect

    Tureav, V.G. )

    1992-06-01

    The aim of this paper is to give a concise introduction to the theory of knot invariants and 3-manifold invariants which generalize the Jones polynomial and which may be considered as a mathematical version of the Witten invariants. Such a theory was introduced by N. Reshetikhin and the author on the ground of the theory of quantum groups. here we use more general algebraic objects, specifically, ribbon and modular categories. Such categories in particular arise as the categories of representations of quantum groups. The notion of modular category, interesting in itself, is closely related to the notion of modular tensor category in the sense of G. Moore and N. Seiberg. For simplicity we restrict ourselves in this paper to the case of closed 3-manifolds.

  13. A Modular PMAD System for Small Spacecraft

    NASA Technical Reports Server (NTRS)

    Button, Robert M.

    1998-01-01

    Current trends in satellite design are focused on developing small, reliable, and inexpensive spacecraft. To that end, a modular power management and distribution system (PMAD) is proposed which will help transition the aerospace industry towards an assembly line approach to building spacecraft. The modular system is based on an innovative DC voltage boost converter called the Series Connected Boost Regulator (SCBR). The SCBR uses existing DC-DC converters and adds a unique series connection. This simple modification provides the SCBR topology with many advantages over existing boost converters. Efficiencies of 94-98%, power densities above 1,000 We/kg, and inherent fault tolerance are just a few of the characteristics presented. Limitations of the SCBR technology are presented, and it is shown that the SCBR makes an ideal photovoltaic array regulator. A modular design based on the series connected boost unit is outlined and functional descriptions of the components are given.

  14. An Integrated Modular Avionics Development Environment

    NASA Astrophysics Data System (ADS)

    Schoofs, T.; Santos, S.; Tatibana, C.; Anjos, J.; Rufino, J.; Windsor, J.

    2009-05-01

    The ARINC 653 standard has taken a leading role within the aeronautical industry in the development of safety-critical systems based upon the Integrated Modular Avionics (IMA) concept. The related cost savings in reduced integration, verification and validation effort has raised interest in the European space industry for developing a spacecraft IMA approach and for the definition of an ARINC 653-for-Space software framework. As part of this process, it is necessary to establish an effective way to develop, test and analyse on-board applications without having access to the final IMA target platform for all engineers. Target platforms are usually extremely expensive considering hardware and software prices as well as training costs. This paper describes the architecture of an Integrated Modular Avionics Development Environment (IMADE) based on the Linux Operating System and the ARINC 653 simulator for Modular On-Board Applications that was developed by Skysoft Portugal, S.A. In cooperation with ESA, 2007-2008.

  15. Modularity and community structure in networks.

    PubMed

    Newman, M E J

    2006-06-01

    Many networks of interest in the sciences, including social networks, computer networks, and metabolic and regulatory networks, are found to divide naturally into communities or modules. The problem of detecting and characterizing this community structure is one of the outstanding issues in the study of networked systems. One highly effective approach is the optimization of the quality function known as "modularity" over the possible divisions of a network. Here I show that the modularity can be expressed in terms of the eigenvectors of a characteristic matrix for the network, which I call the modularity matrix, and that this expression leads to a spectral algorithm for community detection that returns results of demonstrably higher quality than competing methods in shorter running times. I illustrate the method with applications to several published network data sets. PMID:16723398

  16. Modularization Technology in Power Plant Construction

    SciTech Connect

    Kenji Akagi; Kouichi Murayama; Miki Yoshida; Junichi Kawahata

    2002-07-01

    Since the early 1980's, Hitachi has been developing and applying modularization technology to domestic nuclear power plant construction, and has achieved great rationalization. Modularization is one of the plant construction techniques which enables us to reduce site labor by pre-assembling components like equipment, pipes, valves and platforms in congested areas and installing them using large capacity cranes for cost reduction, better quality, safety improvement and shortening of construction time. In this paper, Hitachi's modularization technologies are described especially from with respect to their sophisticated design capabilities. The application of 3D-CAD at the detailed layout design stage, concurrent design environment achieved by the computer network, module design quantity control and the management system are described. (authors)

  17. Eigenvector dynamics under perturbation of modular networks

    NASA Astrophysics Data System (ADS)

    Sarkar, Somwrita; Chawla, Sanjay; Robinson, P. A.; Fortunato, Santo

    2016-06-01

    Rotation dynamics of eigenvectors of modular network adjacency matrices under random perturbations are presented. In the presence of q communities, the number of eigenvectors corresponding to the q largest eigenvalues form a "community" eigenspace and rotate together, but separately from that of the "bulk" eigenspace spanned by all the other eigenvectors. Using this property, the number of modules or clusters in a network can be estimated in an algorithm-independent way. A general argument and derivation for the theoretical detectability limit for sparse modular networks with q communities is presented, beyond which modularity persists in the system but cannot be detected. It is shown that for detecting the clusters or modules using the adjacency matrix, there is a "band" in which it is hard to detect the clusters even before the theoretical detectability limit is reached, and for which the theoretically predicted detectability limit forms the sufficient upper bound. Analytic estimations of these bounds are presented and empirically demonstrated.

  18. PERMEATION OF MULTIFUNCTIONAL ACRYLATES THROUGH THREE PROTECTIVE CLOTHING MATERIALS

    EPA Science Inventory

    Permeation tests were conducted with trimethylolpropane triacrylate TMPTA), 1,6-hexanediol diacrylate (HDDA), and two mixtures of 1,6-hexanediol diacrylate with 2-ethylhexyl acrylate (EHA) to better understand the permeation behavior of multifunctional acrylate compounds. he test...

  19. PERMEATION OF MULTIFUNCTIONAL ACRYLATES THROUGH SELECTED PROTECTIVE GLOVE MATERIALS

    EPA Science Inventory

    In support of the Premanufacture Notification (PMN) program of the Environmental Protection Agency's Office of Toxic Substances, the resistance of three glove materials to permeation by multifunctional acrylate compounds was evaluated through a program for the Office of Research ...

  20. The modular structure of informational sequences.

    PubMed

    Schmitt, A O; Ebeling, W; Herzel, H

    1996-01-01

    It is shown that DNA sequences can be decomposed into smaller units much the same as texts can be decomposed into syllables, words, or groups of words. Those smaller units (modules) are extracted from DNA sequences according to statistical criteria. Tests with sequences of known modular structure (two novels and a FORTRAN source code) were performed. The rate to which DNA sequences can be decomposed into modules (modularity) turns out to be a very sensitive measure to distinguish DNA sequences from random sequences. PMID:8924645